U.S. patent application number 12/586070 was filed with the patent office on 2011-06-23 for frozen compositions and methods for piercing a substrate.
This patent application is currently assigned to Searete LLC, a limited liability corporation of the State of Delaware. Invention is credited to Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney, Lowell L. Wood, JR..
Application Number | 20110150765 12/586070 |
Document ID | / |
Family ID | 46332330 |
Filed Date | 2011-06-23 |
United States Patent
Application |
20110150765 |
Kind Code |
A1 |
Boyden; Edward S. ; et
al. |
June 23, 2011 |
Frozen compositions and methods for piercing a substrate
Abstract
Certain embodiments disclosed herein relate to compositions,
methods, devices, systems, and products regarding frozen particles.
In certain embodiments, the frozen particles include materials at
low temperatures. In certain embodiments, the frozen particles
provide vehicles for delivery of particular agents. In certain
embodiments, the frozen particles are administered to at least one
biological tissue.
Inventors: |
Boyden; Edward S.;
(Cambridge, MA) ; Cook; Daniel B.; (Seattle,
WA) ; Hyde; Roderick A.; (Redmond, WA) ;
Leuthardt; Eric C.; (St. Louis, MO) ; Myhrvold;
Nathan P.; (Bellevue, WA) ; Sweeney; Elizabeth
A.; (Seattle, WA) ; Wood, JR.; Lowell L.;
(Bellevue, WA) |
Assignee: |
Searete LLC, a limited liability
corporation of the State of Delaware
|
Family ID: |
46332330 |
Appl. No.: |
12/586070 |
Filed: |
September 15, 2009 |
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Current U.S.
Class: |
424/9.1 ;
424/1.49; 424/130.1; 424/203.1; 435/29; 435/325; 435/395; 435/410;
514/769; 514/772; 600/431; 604/272 |
Current CPC
Class: |
A61K 9/007 20130101;
A61M 37/0015 20130101; C07K 16/283 20130101; A61K 9/0021 20130101;
A61K 9/1688 20130101; A61K 31/505 20130101; C07K 16/22 20130101;
A61P 17/02 20180101; A61K 9/2866 20130101; B33Y 80/00 20141201;
A61K 31/74 20130101; A61K 9/1611 20130101; A61K 39/00 20130101;
A61K 41/0004 20130101; A61K 38/38 20130101; A61K 2039/54 20130101;
C07K 16/2878 20130101; A61K 33/00 20130101; Y02A 50/30 20180101;
A61K 39/145 20130101; A61K 9/19 20130101; A61K 9/209 20130101; A61K
31/00 20130101; C07K 16/30 20130101; A61K 9/1664 20130101; A61K
31/337 20130101; A61K 31/7088 20130101; A61K 39/12 20130101; A61K
9/143 20130101; A61M 2205/02 20130101; G16H 30/40 20180101; A61K
31/519 20130101; A61P 35/00 20180101; G16H 50/20 20180101; G16H
50/50 20180101; A61K 9/2095 20130101; A61K 31/70 20130101; A61K
45/06 20130101; Y10T 83/222 20150401; A61K 9/08 20130101; G16H
20/10 20180101; A61K 9/12 20130101; A61M 2037/0023 20130101; A61M
2037/003 20130101; C12N 2760/16034 20130101; A61K 38/4833 20130101;
A61K 2039/505 20130101; A61P 31/16 20180101; Y02A 90/10 20180101;
A61K 38/4886 20130101; C07K 16/2842 20130101; A61K 31/59 20130101;
A61K 9/1641 20130101; A61K 9/0019 20130101; A61K 31/337 20130101;
A61K 2300/00 20130101; A61M 37/0015 20130101; A61M 2205/02
20130101; A61K 31/70 20130101; A61K 2300/00 20130101; A61K 31/7088
20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/9.1 ;
424/1.49; 424/203.1; 424/130.1; 514/769; 514/772; 435/325; 435/410;
435/395; 435/29; 600/431; 604/272 |
International
Class: |
A61K 49/00 20060101
A61K049/00; A61K 39/395 20060101 A61K039/395; A61K 39/116 20060101
A61K039/116; A61K 47/04 20060101 A61K047/04; C12N 5/07 20100101
C12N005/07; C12N 5/071 20100101 C12N005/071; C12Q 1/02 20060101
C12Q001/02; A61M 5/00 20060101 A61M005/00; A61B 6/00 20060101
A61B006/00; A61P 17/02 20060101 A61P017/02; C12N 5/04 20060101
C12N005/04; A61K 47/20 20060101 A61K047/20; A61K 51/10 20060101
A61K051/10; A61P 35/00 20060101 A61P035/00 |
Claims
1. A frozen piercing implement, comprising: at least one sterile
frozen non-hydrogen oxide solvent and at least one agent; wherein
the frozen piercing implement is configured for piercing at least
one substrate; and wherein the frozen piercing implement is
substantially solid at approximately 65.degree. C., approximately
60.degree. C., approximately 55.degree. C., approximately
50.degree. C., approximately 45.degree. C., approximately
40.degree. C., approximately 37.degree. C., approximately
35.degree. C., approximately 30.degree. C., approximately
25.degree. C., approximately 20.degree. C., approximately
15.degree. C., approximately 10.degree. C., approximately 5.degree.
C., approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween.
2-8. (canceled)
9. The frozen piercing implement of claim 1, wherein the at least
one agent includes at least one of a therapeutic agent, explosive
material, reinforcement agent, adhesive agent, biological
remodeling agent, or abrasive.
10-16. (canceled)
17. The frozen piercing implement of claim 1, wherein the at least
one agent includes one or more components that are inactive.
18. The frozen piercing implement of claim 17, wherein the one or
more components are configured to be activated by
administration.
19. The frozen particle composition of claim 1, wherein the at
least one agent includes one or more of a prodrug or precursor
compound.
20-25. (canceled)
26. The frozen piercing implement of claim 1, further comprising at
least one detection material.
27. The frozen piercing implement of claim 26, wherein the at least
one detection material includes at least one of a contrast agent,
sensor, or electronic identification device.
28. The frozen piercing implement of claim 27, wherein the at least
one electronic identification device includes at least one radio
frequency identification device.
29. The frozen piercing implement of claim 26, wherein the at least
one detection material includes at least one temperature-sensitive
substance.
30. The frozen piercing implement of claim 26, wherein the at least
one detection material includes at least one of a radioactive,
luminescent, colorimetric or odorous substance.
31-32. (canceled)
33. The frozen piercing implement of claim 1, wherein the at least
one frozen piercing implement includes at least one channel.
34-41. (canceled)
42. The frozen piercing implement of claim 33, wherein at least one
surface of the at least one channel is substantially
hydrophobic.
43. The frozen piercing implement of claim 33, wherein at least one
surface of the at least one channel is substantially
hydrophilic.
44-65. (canceled)
66. The frozen piercing implement of claim 1, further including at
least one non-frozen implement holding device.
67. The frozen piercing implement of claim 66, wherein the at least
one non-frozen implement holding device includes at least one
handle, robotic arm, or surgical device.
68-82. (canceled)
83. The frozen piercing implement of claim 1, wherein the frozen
piercing implement includes at least one port.
84. The frozen piercing implement of claim 83, wherein the at least
one port includes at least one side port.
85. The frozen piercing implement of claim 83, wherein the at least
one port includes at least one end port.
86. The frozen piercing implement of claim 83, wherein the at least
one port includes at least one inlet port or outlet port.
87. The frozen piercing implement of claim 83, wherein the at least
one inlet port or outlet port is in fluid communication with at
least one channel.
88-90. (canceled)
91. The frozen piercing implement of claim 1, formulated to be
administered to the at least one substrate.
92. The frozen piercing implement of claim 1, wherein the at least
one substrate includes one or more of a cell, tissue, organ,
structure, device, or food product.
93-96. (canceled)
97. The frozen piercing implement of claim 1, wherein the at least
one frozen piercing implement includes at least one sensor.
98. The frozen piercing implement of claim 97, wherein the at least
one sensor includes at least one sensor configured for detecting at
least one of a biochemical, electrical, optical, functional,
physical, chemical, biological, or structural characteristic of the
at least one material.
99-103. (canceled)
104. The frozen piercing implement of claim 1, further comprising a
plurality of frozen piercing implements.
105. The frozen piercing implement of claim 1, wherein the frozen
piercing implement is included in at least one frozen piercing
implement device.
106. The frozen piercing implement of claim 105, wherein the at
least one frozen piercing implement device includes at least one of
a frozen piercing implement array device, frozen piercing implement
fluidic device, or frozen piercing implement injection device.
107-118. (canceled)
119. A frozen piercing implement, comprising: at least one frozen
agent; wherein the frozen piercing implement is configured for
piercing at least one substrate wherein the frozen piercing
implement is substantially solid at approximately 65.degree. C.,
approximately 60.degree. C., approximately 55.degree. C.,
approximately 50.degree. C., approximately 45.degree. C.,
approximately 40.degree. C., approximately 37.degree. C.,
approximately 35.degree. C., approximately 30.degree. C.,
approximately 25.degree. C., approximately 20.degree. C.,
approximately 15.degree. C., approximately 10.degree. C.,
approximately 5.degree. C., approximately 0.degree. C.,
approximately -5.degree. C., approximately -10.degree. C.,
approximately -15.degree. C., approximately -20.degree. C.,
approximately -25.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -80.degree. C., approximately -90.degree. C.,
approximately -100.degree. C., approximately -120.degree. C.,
approximately -150.degree. C., approximately -170.degree. C.,
approximately -200.degree. C., approximately -250.degree. C., or
any temperature therebetween.
120-233. (canceled)
234. A method of administering at least one frozen piercing
implement to at least one substrate, comprising: contacting at
least one substrate with at least one frozen piercing implement,
wherein the at least one frozen piercing implement includes at
least one sterile non-hydrogen oxide frozen solvent and at least
one agent; and wherein the at least one frozen piercing implement
is substantially solid at approximately 65.degree. C.,
approximately 60.degree. C., approximately 55.degree. C.,
approximately 50.degree. C., approximately 45.degree. C.,
approximately 40.degree. C., approximately 37.degree. C.,
approximately 35.degree. C., approximately 30.degree. C.,
approximately 25.degree. C., approximately 20.degree. C.,
approximately 15.degree. C., approximately 10.degree. C.,
approximately 5.degree. C., approximately 0.degree. C.,
approximately -5.degree. C., approximately -10.degree. C.,
approximately -15.degree. C., approximately -20.degree. C.,
approximately -25.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -80.degree. C., approximately -90.degree. C.,
approximately -100.degree. C., approximately -120.degree. C.,
approximately -150.degree. C., approximately -170.degree. C.,
approximately -200.degree. C., approximately -250.degree. C., or
any temperature therebetween.
235-244. (canceled)
245. The method of claim 234, wherein the at least one substrate
includes one or more of a cell, tissue, organ, structure, device,
or food product.
246. The method of claim 245, wherein the structure includes one or
more of a prosthesis, cell scaffold, or tissue scaffold.
247. The method of claim 245, wherein the device includes at least
one mechanical or electrical device.
248. The method of claim 234, wherein the substrate includes at
least a portion of which is naturally, artificially, or
synthetically derived.
249. The method of claim 234, wherein the substrate includes at
least a portion of which is genetically altered.
250. The method of claim 234, wherein the at least one substrate is
located in at least one of in situ, in vitro, in vivo, in utero, in
planta, in silico, or ex vivo.
251-256. (canceled)
257. The method of claim 234, wherein the at least one substrate
includes one or more of a stalk, stem, leaf, root, plant, or
tendril.
258-261. (canceled)
262. The method of claim 234, wherein the at least one substrate
includes at least one cell mass.
263. The method of claim 234, wherein the at least one substrate
includes one or more wounds.
264. The method of claim 234, wherein the at least one substrate
includes at least a portion of at least one subject.
265. The method of claim 234, wherein the administering at least
one frozen piercing implement includes self-administering the at
least one frozen piercing implement by the at least one
subject.
266-268. (canceled)
269. The method of claim 234, wherein administering the at least
one frozen piercing implement to at least one substrate includes
accelerating, propelling, pushing, pulling, or ejecting the at
least one frozen piercing implement toward the at least one
substrate.
270-272. (canceled)
273. The method of claim 234, further comprising varying the rate,
velocity, force, or angle at which the at least one frozen piercing
implement is administered to the at least one substrate.
274-278. (canceled)
279. The method of claim 234, further comprising administering to
the at least one substrate at least one article including an
optical, photonic, or electronic article.
280. The method of claim 279, wherein the at least one article is
configured to communicate with at least one computer system.
281. The method of claim 279, wherein the at least one article is
configured to monitor at least one characteristic of the at least
one substrate.
282-283. (canceled)
284. The method of claim 279, wherein the at least one article
includes at least one electronic identification device.
285. The method of claim 284, wherein the at least one electronic
identification device includes at least one radio frequency
identification device.
286-290. (canceled)
291. The method of claim 234, further comprising sensing or
extracting at least one material from the at least one
substrate.
292-295. (canceled)
296. The method of claim 234, further comprising withdrawing the at
least one frozen piercing implement from the at least one
substrate.
297. A method of administering at least one frozen piercing
implement to at least one substrate, comprising: contacting at
least one substrate with at least one frozen piercing implement,
wherein the at least one frozen piercing implement includes at
least one frozen agent; and wherein the at least one frozen
piercing implement is substantially solid at approximately
65.degree. C., approximately 60.degree. C., approximately
55.degree. C., approximately 50.degree. C., approximately
45.degree. C., approximately 40.degree. C., approximately
37.degree. C., approximately 35.degree. C., approximately
30.degree. C., approximately 25.degree. C., approximately
20.degree. C., approximately 15.degree. C., approximately
10.degree. C., approximately 5.degree. C., approximately 0.degree.
C., approximately -5.degree. C., approximately -10.degree. C.,
approximately -15.degree. C., approximately -20.degree. C.,
approximately -25.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -80.degree. C., approximately -90.degree. C.,
approximately -100.degree. C., approximately -120.degree. C.,
approximately -150.degree. C., approximately -170.degree. C.,
approximately -200.degree. C., approximately -250.degree. C., or
any temperature therebetween.
298-313. (canceled)
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is related to and claims the benefit
of the earliest available effective filing date(s) from the
following listed application(s) (the "Related Applications") (e.g.,
claims earliest available priority dates for other than provisional
patent applications or claims benefits under 35 USC .sctn.119(e)
for provisional patent applications, for any and all parent,
grandparent, great-grandparent, etc. applications of the Related
Application(s)). All subject matter of the Related Applications and
of any and all parent, grandparent, great-grandparent, etc.
applications of the Related Applications is incorporated herein by
reference to the extent such subject matter is not inconsistent
herewith.
RELATED APPLICATIONS
[0002] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/290,671, entitled COMPOSITIONS AND
METHODS FOR THERAPEUTIC DELIVERY WITH FROZEN PARTICLES, naming
Edward S. Boyden, Roderick A. Hyde, Eric C. Leuthardt, Nathan P.
Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 31 Oct. 2008, which is currently co-pending, or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date. [0003] For purposes of
the USPTO extra-statutory requirements, the present application
constitutes a continuation-in-part of U.S. patent application Ser.
No. 12/290,683, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. [0004] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,685, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. [0005] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,686, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. [0006] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,690, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. [0007] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,691, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. [0008] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,684, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. [0009] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,670, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. [0010] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,664, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. [0011] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,659, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. [0012] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,658, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. [0013] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,665, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. [0014] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,677, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. [0015] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,687, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. [0016] For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,676, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date.
[0017] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/383,264, entitled COMPOSITIONS AND
METHODS FOR DELIVERY OF FROZEN PARTICLE ADHESIVES, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 20 Mar. 2009, which is currently co-pending, or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date.
[0018] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/383,263, entitled COMPOSITIONS AND
METHODS FOR DELIVERY OF FROZEN PARTICLE ADHESIVES, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 20 Mar. 2009, which is currently co-pending, or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date.
[0019] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/383,260, entitled COMPOSITIONS AND
METHODS FOR DELIVERY OF FROZEN PARTICLE ADHESIVES, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 20 Mar. 2009, which is currently co-pending, or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date.
[0020] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/383,265, entitled COMPOSITIONS AND
METHODS FOR DELIVERY OF FROZEN PARTICLE ADHESIVES, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 20 Mar. 2009, which is currently co-pending, or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date.
[0021] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/383,851, entitled COMPOSITIONS AND
METHODS FOR ADMINISTERING COMPARTMENTALIZED FROZEN PARTICLES,
naming Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 27 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0022] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/383,863, entitled COMPOSITIONS AND
METHODS FOR ADMINISTERING COMPARTMENTALIZED FROZEN PARTICLES,
naming Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 27 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0023] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/383,821, entitled COMPOSITIONS AND
METHODS FOR ADMINISTERING COMPARTMENTALIZED FROZEN PARTICLES,
naming Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 27 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0024] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/383,829, entitled COMPOSITIONS AND
METHODS FOR ADMINISTERING COMPARTMENTALIZED FROZEN PARTICLES,
naming Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 27 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0025] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/384,202, entitled COMPOSITIONS AND
METHODS FOR BIOLOGICAL REMODELING WITH FROZEN PARTICLES, naming
Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 31 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0026] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/384,201, entitled COMPOSITIONS AND
METHODS FOR BIOLOGICAL REMODELING WITH FROZEN PARTICLES, naming
Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 31 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0027] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/384,212, entitled COMPOSITIONS AND
METHODS FOR BIOLOGICAL REMODELING WITH FROZEN PARTICLES, naming
Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 31 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0028] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/384,215, entitled COMPOSITIONS AND
METHODS FOR BIOLOGICAL REMODELING WITH FROZEN PARTICLES, naming
Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 31 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0029] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/384,218, entitled COMPOSITIONS AND
METHODS FOR BIOLOGICAL REMODELING WITH FROZEN PARTICLES, naming
Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 31 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0030] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/384,214, entitled COMPOSITIONS AND
METHODS FOR BIOLOGICAL REMODELING WITH FROZEN PARTICLES, naming
Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 31 Mar. 2009, which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date.
[0031] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. to be assigned, Docket No.
0508-004-003-000000, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date.
[0032] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. to be assigned, Docket No.
0508-004-003A-000000, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date.
[0033] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. to be assigned, Docket No.
0508-004-003C-000000, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date.
[0034] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. to be assigned, Docket No.
0508-004-003D-000000, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date.
[0035] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. to be assigned, Docket No.
0508-004-003E-000000, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date.
[0036] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. to be assigned, Docket No.
0508-004-003F-000000, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date.
[0037] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. to be assigned, Docket No.
0508-004-003G-000000, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date.
[0038] The United States Patent Office (USPTO) has published a
notice to the effect that the USPTO's computer programs require
that patent applicants reference both a serial number and indicate
whether an application is a continuation or continuation-in-part.
Stephen G. Kunin, Benefit of Prior-Filed Application, USPTO
Official Gazette Mar. 18, 2003, available at
http://www.uspto.gov/web/offices/com/sol/og/2003/week11/patbene.htm.
The present Applicant Entity (hereinafter "Applicant") has provided
above a specific reference to the application(s) from which
priority is being claimed as recited by statute. Applicant
understands that the statute is unambiguous in its specific
reference language and does not require either a serial number or
any characterization, such as "continuation" or
"continuation-in-part," for claiming priority to U.S. patent
applications. Notwithstanding the foregoing, Applicant understands
that the USPTO's computer programs have certain data entry
requirements, and hence Applicant is designating the present
application as a continuation-in-part of its parent applications as
set forth above, but expressly points out that such designations
are not to be construed in any way as any type of commentary and/or
admission as to whether or not the present application contains any
new matter in addition to the matter of its parent
application(s).
SUMMARY
[0039] Compositions, methods, systems, and other embodiments
related to one or more frozen particle compositions are described
herein. In one embodiment, frozen particle compositions, frozen
piercing implements, or frozen piercing implement devices are
described.
[0040] In one embodiment, a frozen piercing implement comprising a
sterile frozen implement configured for piercing at least one
substrate is described. In one embodiment, a frozen piercing
implement, comprises: a sterile frozen hydrogen oxide implement
configured for piercing at least part of at least one substrate. In
one embodiment, the sterile frozen hydrogen oxide implement
includes at least one agent.
[0041] In one embodiment, a method of administering at least one
frozen piercing implement to at least one substrate comprises:
contacting at least one substrate with at least one frozen piercing
implement. In one embodiment, the at least one frozen piercing
implement includes sterile frozen hydrogen oxide. In one
embodiment, a method of vaccinating a subject comprises:
administering to a subject at least one frozen piercing implement.
In one embodiment, the at least one frozen piercing implement
includes sterile frozen hydrogen oxide and at least one vaccine. In
one embodiment, a method comprises: delivering at least one agent
to at least one substrate; wherein the at least one agent is
included in at least one sterile frozen hydrogen oxide piercing
implement. In one embodiment, a method for piercing at least one
substrate comprises: piercing at least one substrate with a frozen
piercing implement including sterile frozen hydrogen oxide and at
least one agent.
[0042] In one embodiment, a frozen piercing implement, comprises:
at least one sterile frozen solution, the solution including at
least one agent; wherein the frozen piercing implement is
configured for piercing at least part of at least one substrate. In
one embodiment, a method of administering at least one frozen
piercing implement to at least one substrate, comprises: contacting
at least one substrate with at least one frozen piercing implement,
wherein the at least one frozen piercing implement includes at
least one sterile frozen solution, the solution including at least
one agent. In one embodiment, a method of vaccinating a subject,
comprises: administering to a subject at least one frozen piercing
implement; wherein the at least one frozen piercing implement
includes at least one sterile frozen solution, the solution
including at least one vaccine.
[0043] In one embodiment, a frozen piercing implement comprises: at
least one non-hydrogen oxide frozen solvent; wherein the frozen
piercing implement is configured for piercing at least one
substrate; and wherein the frozen piercing implement is
substantially solid at approximately 65.degree. C., approximately
60.degree. C., approximately 55.degree. C., approximately
50.degree. C., approximately 45.degree. C., approximately
40.degree. C., approximately 37.degree. C., approximately
35.degree. C., approximately 30.degree. C., approximately
25.degree. C., approximately 20.degree. C., approximately
15.degree. C., approximately 10.degree. C., approximately 5.degree.
C., approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween. In
one embodiment, the at least one non-hydrogen oxide frozen solvent
is sterile. In one embodiment, the at least one non-hydrogen oxide
frozen solvent includes at least one agent
[0044] In one embodiment, a frozen piercing implement, comprises:
at least one frozen agent; and wherein the frozen piercing
implement is configured for piercing at least one substrate wherein
the frozen piercing implement is substantially solid at
approximately 65.degree. C., approximately 60.degree. C.,
approximately 55.degree. C., approximately 50.degree. C.,
approximately 45.degree. C., approximately 40.degree. C.,
approximately 37.degree. C., approximately 35.degree. C.,
approximately 30.degree. C., approximately 25.degree. C.,
approximately 20.degree. C., approximately 15.degree. C.,
approximately 10.degree. C., approximately 5.degree. C.,
approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween.
[0045] In one embodiment, a method of administering at least one
frozen piercing implement to at least one substrate, comprises:
contacting at least one substrate with at least one frozen piercing
implement, wherein the at least one frozen piercing implement
includes at least one non-hydrogen oxide frozen solvent; and
wherein the at least one frozen piercing implement is substantially
solid at approximately 65.degree. C., approximately 60.degree. C.,
approximately 55.degree. C., approximately 50.degree. C.,
approximately 45.degree. C., approximately 40.degree. C.,
approximately 37.degree. C., approximately 35.degree. C.,
approximately 30.degree. C., approximately 25.degree. C.,
approximately 20.degree. C., approximately 15.degree. C.,
approximately 10.degree. C., approximately 5.degree. C.,
approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween. In
one embodiment, the at least one non-hydrogen oxide frozen solvent
is sterile. In one embodiment, the at least one non-hydrogen oxide
frozen solvent includes at least one agent.
[0046] In one embodiment, a method of administering at least one
frozen piercing implement to at least one substrate,
comprises:contacting at least one substrate with at least one
frozen piercing implement, wherein the at least one frozen piercing
implement includes at least one agent; and wherein the at least one
frozen piercing implement is substantially solid at approximately
65.degree. C., approximately 60.degree. C., approximately
55.degree. C., approximately 50.degree. C., approximately
45.degree. C., approximately 40.degree. C., approximately
37.degree. C., approximately 35.degree. C., approximately
30.degree. C., approximately 25.degree. C., approximately
20.degree. C., approximately 15.degree. C., approximately
10.degree. C., approximately 5.degree. C., approximately 0.degree.
C., approximately -5.degree. C., approximately -10.degree. C.,
approximately -15.degree. C., approximately -20.degree. C.,
approximately -25.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -80.degree. C., approximately -90.degree. C.,
approximately -100.degree. C., approximately -120.degree. C.,
approximately -150.degree. C., approximately -170.degree. C.,
approximately -200.degree. C., approximately -250.degree. C., or
any temperature therebetween.
[0047] In one embodiment, a method of vaccinating a subject,
comprises: administering to a subject at least one frozen piercing
implement; wherein the at least one frozen piercing implement
includes at least one non-hydrogen oxide frozen solvent and at
least one vaccine; and wherein the at least one frozen piercing
implement is substantially solid at approximately 65.degree. C.,
approximately 60.degree. C., approximately 55.degree. C.,
approximately 50.degree. C., approximately 45.degree. C.,
approximately 40.degree. C., approximately 37.degree. C.,
approximately 35.degree. C., approximately 30.degree. C.,
approximately 25.degree. C., approximately 20.degree. C.,
approximately 15.degree. C., approximately 10.degree. C.,
approximately 5.degree. C., approximately 0.degree. C.,
approximately -5.degree. C., approximately -10.degree. C.,
approximately -15.degree. C., approximately -20.degree. C.,
approximately -25.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -80.degree. C., approximately -90.degree. C.,
approximately -100.degree. C., approximately -120.degree. C.,
approximately -150.degree. C., approximately -170.degree. C.,
approximately -200.degree. C., approximately -250.degree. C., or
any temperature therebetween. In one embodiment, a method of
vaccinating a subject, comprises: administering to a subject at
least one frozen vaccine piercing implement; wherein the at least
one frozen piercing implement is substantially solid at
approximately 65.degree. C., approximately 60.degree. C.,
approximately 55.degree. C., approximately 50.degree. C.,
approximately 45.degree. C., approximately 40.degree. C.,
approximately 37.degree. C., approximately 35.degree. C.,
approximately 30.degree. C., approximately 25.degree. C.,
approximately 20.degree. C., approximately 15.degree. C.,
approximately 10.degree. C., approximately 5.degree. C.,
approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween. In
one embodiment, the at least one frozen piercing implement is
sterile. In one embodiment, the at least one frozen piercing
implement includes at least one agent.
[0048] In one embodiment, a frozen piercing implement, comprises:
at least one sterile frozen component and at least one agent;
wherein the at least one component is substantially in a gaseous
state at or above approximately 0.25 bar, approximately 0.5 bar,
approximately 1.0 bar, approximately 5.0 bar, approximately 10.0
bar, approximately 25 bar, approximately 50 bar, approximately 100
bar, approximately 200 bar, or approximately 500 bar pressure; and
at or above approximately 10.degree. C., approximately 15.degree.
C., approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 37.degree. C.,
approximately 40.degree. C., approximately 45.degree. C., or
approximately 50.degree. C.; and wherein the at least one frozen
piercing implement is configured for piercing at least one
substrate.
[0049] In one embodiment, a method of administering at least one
frozen piercing implement to at least one substrate, comprises:
contacting at least one substrate with at least one frozen piercing
implement, wherein the at least one frozen piercing implement
includes at least one sterile frozen component and at least one
agent; wherein the at least one sterile frozen component is in a
gaseous state at approximately 0.25 bar, approximately 0.5 bar,
approximately 1.0 bar, approximately 5.0 bar, approximately 10.0
bar, approximately 25 bar, approximately 50 bar, approximately 100
bar, approximately 200 bar, or approximately 500 bar pressure; and
at or above approximately 10.degree. C., approximately 15.degree.
C., approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 37.degree. C.,
approximately 40.degree. C., approximately 45.degree. C., or
approximately 50.degree. C.; and wherein the at least one frozen
piercing implement is configured for piercing the at least one
substrate.
[0050] In one embodiment, a method of vaccinating a subject,
comprises: administering to a subject at least one frozen piercing
implement; wherein the at least one frozen piercing implement
includes at least one sterile frozen component and at least one
agent; and wherein the at least one sterile frozen component is in
a gaseous state at approximately 0.25 bar, approximately 0.5 bar,
approximately 1.0 bar, approximately 5.0 bar, approximately 10.0
bar, approximately 25 bar, approximately 50 bar, approximately 100
bar, approximately 200 bar, or approximately 500 bar pressure; and
at or above approximately 10.degree. C., approximately 15.degree.
C., approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 37.degree. C.,
approximately 40.degree. C., approximately 45.degree. C., or
approximately 50.degree. C.; and wherein the at least one frozen
piercing implement is configured for piercing at least one
substrate.
[0051] In one embodiment, an array device comprises: a support
structure having a surface; and a plurality of sterile frozen
piercing implements extending substantially outward from the
support structure. In one embodiment, an array device, comprises: a
support structure having a surface; a plurality of piercing
implements extending substantially outward from the surface of the
support structure; wherein at least one piercing implement of the
plurality of piercing implements includes a frozen piercing
implement. In one embodiment, a composition, comprises: a plurality
of piercing implement array devices joined together, the piercing
implement array devices including at least one frozen piercing
implement. In one embodiment, a composition, comprises: a support
means for an array device; wherein the array device includes one or
more frozen piercing implements. In one embodiment, a method of
administering at least one array device to at least one substrate,
comprises: contacting at least one array device to at least one
substrate, wherein the array device includes at least one frozen
piercing implement.
[0052] In one embodiment, a method of vaccinating a subject,
comprises: administering to a subject at least one frozen piercing
implement array device; wherein the at least one frozen piercing
implement array device includes at least one frozen piercing
implement including at least one vaccine.
[0053] In one embodiment, a fluidic device, comprises: a support
structure at least partially defining at least one compartment; and
at least one frozen piercing implement in fluid communication with
the at least one compartment. As described herein, in one
embodiment, the at least one frozen piercing implement has at least
one major dimension of approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer, or any value
therebetween.
[0054] In one embodiment, a fluidic device, comprises: at least one
frozen piercing implement, and at least one actuator configured to
actuate the at least one frozen piercing implement. As described
herein, in one embodiment, at least one frozen piercing implement
has at least one major dimension of approximately one centimeter or
less, approximately one millimeter or less, approximately one
micrometer or less, approximately one nanometer, or any value
therebetween.
[0055] In one embodiment, the fluidic device further comprises a
plurality of frozen piercing implements, and at least one actuator
configured to actuate the plurality of frozen piercing implements;
wherein each piercing implement has at least one major dimension of
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer, or any value therebetween.
[0056] Various computer-implemented methods, automated devices,
systems, computer program products, and circuitry for any thereof
are provided herein. In one embodiment, instructions for making at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device are provided for various
non-limiting examples. In one embodiment, instructions for
administering at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device are
provided for various non-limiting examples.
[0057] The various embodiments disclosed are described in greater
detail herein.
BRIEF DESCRIPTION OF THE FIGURES
[0058] FIG. 1 illustrates particular phases of hydrogen oxide.
[0059] FIG. 2 illustrates the density of hydrogen oxide at various
pressure points.
[0060] FIG. 3 illustrates particular phases of hydrogen oxide at
various pressure and temperature points.
[0061] FIG. 4 illustrates particular phases of hydrogen oxide at
various pressure and temperature points.
[0062] FIG. 5 illustrates the strength of hydrogen oxide samples
reinforced with fiberglass or kaolin.
[0063] FIG. 6 illustrates the strength of hydrogen oxide samples
reinforced with a reinforcement agent.
[0064] FIG. 7 illustrates a partial view of a method 700 that
includes generating at least one response.
[0065] FIG. 8 illustrates a partial view of FIG. 7 in which
embodiments may be implemented.
[0066] FIG. 9 illustrates a partial view of FIG. 7 in which
embodiments may be implemented.
[0067] FIG. 10 illustrates a partial view of a method 1000 that
includes generating at least one response.
[0068] FIG. 11 illustrates a partial view of FIG. 10 in which
embodiments may be implemented.
[0069] FIG. 12 illustrates a partial view of FIG. 10 in which
embodiments may be implemented.
[0070] FIG. 13 illustrates a partial view of a system 1300 that
includes a computer program for executing a computing process on a
computing device.
[0071] FIG. 14 illustrates a partial view of FIG. 13 in which
embodiments may be implemented.
[0072] FIG. 15 illustrates a partial view of FIG. 13 in which
embodiments may be implemented.
[0073] FIG. 16 illustrates a partial view of a system 1600 that
includes a computer program for executing a computing process on a
computing device.
[0074] FIG. 17 illustrates a partial view of a computer program
product 1700 for executing a computing process on a computing
device.
[0075] FIG. 18 illustrates a partial view of a computer program
product 1800 for executing a computing process on a computing
device.
[0076] FIG. 19 illustrates a partial view of a computer program
product 1900 for executing a computing process on a computing
device.
[0077] FIG. 20 illustrates a partial view of a computer program
product 2000 for executing a computing process on a computing
device.
[0078] FIG. 21 illustrates a partial view of a computer program
product 2100 for executing a computing process on a computing
device.
[0079] FIG. 22 illustrates a partial view of a computer program
product 2200 for executing a computing process on a computing
device.
[0080] FIG. 23 illustrates a partial view of a method 2300 that
includes generating at least one response.
[0081] FIG. 24 illustrates a partial view FIG. 23 in which
embodiments may be implemented.
[0082] FIG. 25 illustrates a partial view FIG. 23 in which
embodiments may be implemented.
[0083] FIG. 26 illustrates a partial view of a method 2600 that
includes generating at least one response.
[0084] FIG. 27 illustrates a partial view of FIG. 26 in which
embodiments may be implemented.
[0085] FIG. 28 illustrates a partial view of FIG. 26 in which
embodiments may be implemented.
[0086] FIG. 29 illustrates a partial view of a system 2900 that
includes a computer program for executing a computing process on a
computing device.
[0087] FIG. 30 illustrates a partial view of FIG. 29 in which
embodiments may be implemented.
[0088] FIG. 31 illustrates a partial view of a system 3100 that
includes a computer program for executing a computing process on a
computing device.
[0089] FIG. 32 illustrates a partial view of FIG. 31 in which
embodiments may be implemented.
[0090] FIG. 33 illustrates a partial view of a system 3300 that
includes a computer program for executing a computing process on a
computing device.
[0091] FIG. 34 illustrates a partial view of FIG. 33 in which
embodiments may be implemented.
[0092] FIG. 35 illustrates a partial view of FIG. 33 in which
embodiments may be implemented.
[0093] FIG. 36 illustrates a partial view of a system 3600 that
includes a computer program for executing a computing process on a
computing device.
[0094] FIG. 37 illustrates a partial view of a method 3700 in which
embodiments may be implemented.
[0095] FIG. 38 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0096] FIG. 39 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0097] FIG. 40 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0098] FIG. 41 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0099] FIG. 42 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0100] FIG. 43 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0101] FIG. 44 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0102] FIG. 45 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0103] FIG. 46 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0104] FIG. 47 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0105] FIG. 48 illustrates a partial view of FIG. 37 in which
embodiments may be implemented.
[0106] FIG. 49 illustrates a partial view of a method 4900 in which
embodiments may be implemented.
[0107] FIG. 50 illustrates a partial view of FIG. 49 in which
embodiments may be implemented.
[0108] FIG. 51 illustrates a partial view of FIG. 49 in which
embodiments may be implemented.
[0109] FIG. 52 illustrates a partial view of FIG. 49 in which
embodiments may be implemented.
[0110] FIG. 53 illustrates a partial view of FIG. 49 in which
embodiments may be implemented.
[0111] FIG. 54 illustrates a partial view of a method 5400 in which
embodiments may be implemented.
[0112] FIG. 55 illustrates a partial view of FIG. 54 in which
embodiments may be implemented.
[0113] FIG. 56 illustrates a partial view of FIG. 54 in which
embodiments may be implemented.
[0114] FIG. 57 illustrates a partial view of FIG. 54 in which
embodiments may be implemented.
[0115] FIG. 58 illustrates a partial view of FIG. 54 in which
embodiments may be implemented.
[0116] FIG. 59 illustrates a partial view of a method 5900 in which
embodiments may be implemented.
[0117] FIG. 60 illustrates a partial view of a method 6000 in which
embodiments may be implemented.
[0118] FIG. 61 illustrates a partial view of FIG. 60 in which
embodiments may be implemented.
[0119] FIG. 62 illustrates a partial view of FIG. 60 in which
embodiments may be implemented.
[0120] FIG. 63 illustrates a partial view of FIG. 60 in which
embodiments may be implemented.
[0121] FIG. 64 illustrates a partial view of FIG. 60 in which
embodiments may be implemented.
[0122] FIG. 65 illustrates a partial view of FIG. 60 in which
embodiments may be implemented.
[0123] FIG. 66 illustrates a partial view of a method 6600 in which
embodiments may be implemented.
[0124] FIG. 67 illustrates a partial view of FIG. 66 in which
embodiments may be implemented.
[0125] FIG. 68 illustrates a partial view of FIG. 66 in which
embodiments may be implemented.
[0126] FIG. 69 illustrates a partial view of FIG. 66 in which
embodiments may be implemented.
[0127] FIG. 70 illustrates a partial view of FIG. 66 in which
embodiments may be implemented.
[0128] FIG. 71 illustrates a partial view of FIG. 66 in which
embodiments may be implemented.
[0129] FIG. 72 illustrates a partial view of FIG. 66 in which
embodiments may be implemented.
[0130] FIG. 73 illustrates a partial view of a system 7300 in which
embodiments may be implemented.
[0131] FIG. 74 illustrates a partial view of FIG. 73 in which
embodiments may be implemented.
[0132] FIG. 75 illustrates a partial view of a system 7510 in which
embodiments may be implemented.
[0133] FIG. 76 illustrates a partial view of FIG. 75 in which
embodiments may be implemented.
[0134] FIG. 77 illustrates a partial view of a system 7700 in which
embodiments may be implemented.
[0135] FIG. 78 illustrates a partial view of a computer program
product 7800 in which embodiments may be implemented.
[0136] FIG. 79 illustrates a partial view of a system 7900 in which
embodiments may be implemented.
[0137] FIG. 80 illustrates a partial view of a system 8000 in which
embodiments may be implemented.
[0138] FIG. 81 illustrates a partial view of FIG. 80 in which
embodiments may be implemented.
[0139] FIG. 82 illustrates a partial view of a system 8200 in which
embodiments may be implemented.
[0140] FIG. 83 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0141] FIG. 84 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0142] FIG. 85 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0143] FIG. 86 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0144] FIG. 87 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0145] FIG. 88 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0146] FIG. 89 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0147] FIG. 90 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0148] FIG. 91 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0149] FIG. 92 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0150] FIG. 93 illustrates a partial view of FIG. 82 in which
embodiments may be implemented.
[0151] FIG. 94 illustrates a partial view of a system 9400 in which
embodiments may be implemented.
[0152] FIG. 95 illustrates a partial view of FIG. 94 in which
embodiments may be implemented.
[0153] FIG. 96 illustrates a partial view of FIG. 94 in which
embodiments may be implemented.
[0154] FIG. 97 illustrates a partial view of FIG. 94 in which
embodiments may be implemented.
[0155] FIG. 98 illustrates a partial view of FIG. 94 in which
embodiments may be implemented.
[0156] FIG. 99 illustrates a partial view of a system 9900 in which
embodiments may be implemented.
[0157] FIG. 100 illustrates a partial view of FIG. 99 in which
embodiments may be implemented.
[0158] FIG. 101 illustrates a partial view of FIG. 99 in which
embodiments may be implemented.
[0159] FIG. 102 illustrates a partial view of FIG. 99 in which
embodiments may be implemented.
[0160] FIG. 103 illustrates a partial view of FIG. 99 in which
embodiments may be implemented.
[0161] FIG. 104 illustrates a partial view of a system 10400 in
which embodiments may be implemented.
[0162] FIG. 105 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
[0163] FIG. 106 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
[0164] FIG. 107 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
[0165] FIG. 108 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
[0166] FIG. 109 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
[0167] FIG. 110 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
[0168] FIG. 111 illustrates a partial view of a system 11100 in
which embodiments may be implemented.
[0169] FIG. 112 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
[0170] FIG. 113 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
[0171] FIG. 114 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
[0172] FIG. 115 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
[0173] FIG. 116 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
[0174] FIG. 117 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
[0175] FIG. 118 illustrates a partial cross-sectional view of
mammalian skin.
[0176] FIG. 119 illustrates a general phase diagram, including the
critical point and sinodal curve.
[0177] FIG. 120 illustrates the boiling liquid expansion vapor
explosion diagram for carbon dioxide, calculated using the critical
point and sinodal curve.
[0178] FIG. 121 A illustrates particular examples of optional
configurations of embodiments including at least one frozen
particle composition or frozen piercing implement.
[0179] FIG. 121 B illustrates particular examples for
configurations of embodiments including at least one frozen
particle composition or frozen piercing implement with optional at
least one cavity.
[0180] FIG. 121 C illustrates particular examples of optional
configurations of embodiments including at least one frozen
particle composition or frozen piercing implement.
[0181] FIG. 122 illustrates a diagram for a particular force per
implement for amount of displacement.
[0182] FIG. 123 illustrates perspective views of particular
examples of optional configurations of embodiments including at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device.
[0183] FIG. 124 A illustrates an example of an embodiment including
at least one frozen piercing implement or frozen piercing implement
device.
[0184] FIG. 124 B illustrates an example of one embodiment for
making at least one frozen particle composition, frozen piercing
implement or frozen piercing implement device.
[0185] FIG. 124 C illustrates an example of one embodiment for
making at least one frozen particle composition, frozen piercing
implement or frozen piercing implement device.
[0186] FIG. 124 D illustrates an example of one embodiment for
making at least one frozen particle composition, frozen piercing
implement or frozen piercing implement device.
[0187] FIG. 124 E illustrates an example of one embodiment for
making at least one frozen particle composition, frozen piercing
implement or frozen piercing implement device.
[0188] FIG. 124 F illustrates an example of one embodiment for
making at least one frozen particle composition, frozen piercing
implement or frozen piercing implement device.
[0189] FIG. 124 G illustrates an example of one embodiment for
making at least one frozen particle composition, frozen piercing
implement or frozen piercing implement device.
[0190] FIG. 125 A illustrates cross-sectional view of a piercing
implement including one or more functionalized surfaces, and
optional channel, according to some illustrated embodiments.
[0191] FIG. 125 B illustrates cross-sectional view of a piercing
implement including one or more functionalized surfaces, and
optional channel, according to some illustrated embodiments.
[0192] FIG. 125 C illustrates cross-sectional view of a piercing
implement including one or more functionalized surfaces, and
optional channel, according to some illustrated embodiments.
[0193] FIG. 125 D illustrates an exploded view of the implement
illustrated in FIG. 125 C, including one or more functional groups
in the form of bonded amino groups, according to some illustrated
embodiments.
[0194] FIG. 125 E illustrates an exploded view of an implement,
including one or more functional groups in the form of polisilane
groups, according to some illustrated embodiments.
[0195] FIG. 126 A illustrates a cross-sectional view of a plurality
of implements, according to some illustrated embodiments.
[0196] FIG. 126 B illustrates a cross-sectional view of a plurality
of implements, according to some illustrated embodiments.
[0197] FIG. 126 C illustrates a cross-sectional view of a plurality
of implements, according to some illustrated embodiments.
[0198] FIG. 126 D illustrates a cross-sectional view of a plurality
of implements, according to some illustrated embodiments.
[0199] FIG. 126 E illustrates a cross-sectional view of a plurality
of implements, according to some illustrated embodiments.
[0200] FIG. 126 F illustrates a cross-sectional view of a plurality
of implements, according to some illustrated embodiments.
[0201] FIG. 126 G illustrates a cross-sectional view of a plurality
of implements, according to some illustrated embodiments.
[0202] FIG. 127 A illustrates a cross-sectional view of an
embodiment including at least one frozen piercing implement
device.
[0203] FIG. 127 B illustrates a perspective view of an embodiment
including at least one frozen piercing implement device.
[0204] FIG. 128 A illustrates a cross-sectional view of an
embodiment including at least one frozen piercing implement.
[0205] FIG. 128 B illustrates a perspective view of a plurality of
frozen piercing implements, according to an illustrated
embodiment.
[0206] FIG. 128 C illustrates a perspective view of an embodiment
of at least one frozen piercing implement device.
[0207] FIG. 128 D illustrates a perspective view of an embodiment
of at least one frozen piercing implement device.
[0208] FIG. 129 A illustrates a cross-sectional view of an
embodiment of at least one frozen piercing implement.
[0209] FIG. 129 B illustrates a cross-sectional view of an
embodiment of at least one frozen piercing implement.
[0210] FIG. 130 A illustrates a cross-sectional view of an
embodiment of at least one frozen piercing implement device.
[0211] FIG. 130 B illustrates a cross-sectional view of an
embodiment of at least one frozen piercing implement device.
[0212] FIG. 131 A illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
[0213] FIG. 131 B illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
[0214] FIG. 131 C illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
[0215] FIG. 131 D illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
[0216] FIG. 131 E illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
[0217] FIG. 131 F illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
[0218] FIG. 131 G illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
[0219] FIG. 131 H illustrates a perspective view of an embodiment
including at least one frozen piercing implement device, optionally
including a plurality of frozen piercing implements.
[0220] FIG. 132 illustrates a perspective view of an embodiment
including at least one frozen piercing implement device, optionally
including a plurality of frozen piercing implements.
[0221] FIG. 133 A illustrates a cross-sectional view of an
embodiment including at least one frozen piercing implement device,
optionally including a plurality of frozen piercing implements.
[0222] FIG. 133 B illustrates a cross-sectional view of an
embodiment including at least one frozen piercing implement device,
optionally including a plurality of frozen piercing implements.
[0223] FIG. 134 A illustrates a cross-sectional view of an
embodiment including at least one frozen piercing implement device,
optionally including a plurality of frozen piercing implements.
[0224] FIG. 134 B illustrates a cross-sectional view of an
embodiment including at least one frozen piercing implement device,
optionally including a plurality of frozen piercing implements.
[0225] FIG. 135 illustrates a partial view of a method 13500, in
which embodiments may be implemented.
[0226] FIG. 136 illustrates a partial view of the method of FIG.
135, in which embodiments may be implemented.
[0227] FIG. 137 illustrates a partial view of the method of FIG.
135, in which embodiments may be implemented.
[0228] FIG. 138 illustrates a partial view of the method of FIG.
135, in which embodiments may be implemented.
[0229] FIG. 139 illustrates a partial view of the method of FIG.
135, in which embodiments may be implemented.
[0230] FIG. 140 A-C illustrates a cross-sectional view of an
example of an embodiment of a frozen piercing implement device.
[0231] FIG. 141 illustrates a partial view of a method 14100, in
which embodiments may be implemented.
[0232] FIG. 142 illustrates a partial view of the method of FIG.
141, in which embodiments may be implemented.
[0233] FIG. 143 illustrates a partial view of the method of FIG.
141, in which embodiments may be implemented.
[0234] FIG. 144 illustrates a partial view of the method of FIG.
141, in which embodiments may be implemented.
[0235] FIG. 145 illustrates a partial view of the method of FIG.
141, in which embodiments may be implemented.
[0236] FIG. 146 illustrates a partial view of the method of FIG.
141, in which embodiments may be implemented.
[0237] FIG. 147 illustrates a partial view of the method of FIG.
141, in which embodiments may be implemented.
[0238] FIG. 148 illustrates a partial view of a method 14800, in
which embodiments may be implemented.
[0239] FIG. 149 illustrates a partial view of the method of FIG.
148, in which embodiments may be implemented.
[0240] FIG. 150 illustrates a partial view of the method of FIG.
148, in which embodiments may be implemented.
[0241] FIG. 151 illustrates a partial view of a method 15100, in
which embodiments may be implemented.
[0242] FIG. 152 illustrates a partial view of the method of FIG.
151, in which embodiments may be implemented.
[0243] FIG. 153 illustrates a partial view of the method of FIG.
151, in which embodiments may be implemented.
[0244] FIG. 154 illustrates a partial view of the method of FIG.
151, in which embodiments may be implemented.
[0245] FIG. 155 illustrates a partial view of the method of FIG.
151, in which embodiments may be implemented.
[0246] FIG. 156 illustrates a partial view of the method of FIG.
151, in which embodiments may be implemented.
[0247] FIG. 157 illustrates a partial view of the method of FIG.
151, in which embodiments may be implemented.
[0248] FIG. 158 illustrates a partial view of a method 15800, in
which embodiments may be implemented.
[0249] FIG. 159 illustrates a partial view of the method of FIG.
158, in which embodiments may be implemented.
[0250] FIG. 160 illustrates a partial view of the method of FIG.
158, in which embodiments may be implemented.
[0251] FIG. 161 illustrates a partial view of the method of FIG.
158, in which embodiments may be implemented.
[0252] FIG. 162 illustrates a partial view of a method 16200, in
which embodiments may be implemented.
[0253] FIG. 163 illustrates a partial view of a system 16300, in
which embodiments may be implemented.
[0254] FIG. 164 illustrates partial view of the system of FIG. 163,
in which embodiments may be implemented.
[0255] FIG. 165 illustrates a partial view of the system of FIG.
163, in which embodiments may be implemented.
[0256] FIG. 166 illustrates a partial view of the system of FIG.
163, in which embodiments may be implemented.
[0257] FIG. 167 illustrates a partial view of a system 16700, in
which embodiments may be implemented.
[0258] FIG. 168 illustrates a partial view of the system of FIG.
167, in which embodiments may be implemented.
[0259] FIG. 169 illustrates a partial view of the system of FIG.
167, in which embodiments may be implemented.
[0260] FIG. 170 illustrates a partial view of the system of FIG.
167, in which embodiments may be implemented.
[0261] FIG. 171 illustrates a partial view of the system of FIG.
167, in which embodiments may be implemented.
[0262] FIG. 172 illustrates a partial view of the system of FIG.
167, in which embodiments may be implemented.
[0263] FIG. 173 illustrates a partial view of the system of FIG.
167, in which embodiments may be implemented.
[0264] FIG. 174 illustrates a partial view of the system of FIG.
167, in which embodiments may be implemented.
[0265] FIG. 175 illustrates a partial view of a system 17500, in
which embodiments may be implemented.
[0266] FIG. 176 illustrates a partial view of the system of FIG.
175, in which embodiments may be implemented.
[0267] FIG. 177 illustrates a partial view of the system of FIG.
175, in which embodiments may be implemented.
[0268] FIG. 178 illustrates a partial view of the system of FIG.
175, in which embodiments may be implemented.
[0269] FIG. 179 illustrates a partial view of the system of FIG.
175, in which embodiments may be implemented.
[0270] FIG. 180 illustrates a partial view of the system of FIG.
175, in which embodiments may be implemented.
[0271] FIG. 181 illustrates a partial view of the system FIG. 175,
in which embodiments may be implemented.
[0272] FIG. 182 illustrates a partial view of a system 18200, in
which embodiments may be implemented.
[0273] FIG. 183 illustrates a partial view of the system of FIG.
182, in which embodiments may be implemented.
[0274] FIG. 184 illustrates a partial view of the system of FIG.
182, in which embodiments may be implemented.
[0275] FIG. 185 illustrates a partial view of the system of FIG.
182, in which embodiments may be implemented.
[0276] FIG. 186 illustrates a partial view of a system 18600, in
which embodiments may be implemented.
[0277] FIG. 187 illustrates a partial view of the system of FIG.
186, in which embodiments may be implemented.
[0278] FIG. 188 illustrates a partial view of the system of FIG.
186, in which embodiments may be implemented.
[0279] FIG. 189 illustrates a partial view of the system of FIG.
186, in which embodiments may be implemented.
[0280] FIG. 190 illustrates a partial view of a system 19000, in
which embodiments may be implemented.
[0281] FIG. 191 illustrates a partial view of the system of FIG.
190, in which embodiments may be implemented.
[0282] FIG. 192 illustrates a partial view of the system of FIG.
190, in which embodiments may be implemented.
[0283] FIG. 193 illustrates a partial view of a computer program
product 19300, in which embodiments may be implemented.
[0284] FIG. 194 illustrates a partial view of the computer program
product of FIG. 193, in which embodiments may be implemented.
[0285] FIG. 195 illustrates a partial view of the computer program
product of FIG. 193, in which embodiments may be implemented.
[0286] FIG. 196 illustrates a partial view of a system 19600, in
which embodiments may be implemented.
[0287] FIG. 197 illustrates a partial view of the system of FIG.
196, in which embodiments may be implemented.
[0288] FIG. 198 illustrates a partial view of the system of FIG.
196, in which embodiments may be implemented.
[0289] FIG. 199 illustrates a partial view of a system 19900, in
which embodiments may be implemented.
[0290] FIG. 200 illustrates a partial view of the system of FIG.
199, in which embodiments may be implemented.
[0291] FIG. 201 illustrates a partial view of a system 20100, in
which embodiments may be implemented.
[0292] FIG. 202 illustrates a partial view of the system of FIG.
201, in which embodiments may be implemented.
[0293] FIG. 203 illustrates a partial view of the system of FIG.
201, in which embodiments may be implemented.
[0294] FIG. 204 illustrates a partial view of the system of FIG.
201, in which embodiments may be implemented.
[0295] FIG. 205 illustrates a partial view of a system 20500, in
which embodiments may be implemented.
[0296] FIG. 206 illustrates a partial view of the system of FIG.
205, in which embodiments may be implemented.
[0297] FIG. 207 illustrates a partial view of the system of FIG.
205, in which embodiments may be implemented.
[0298] FIG. 208 illustrates a partial view of the system of FIG.
205, in which embodiments may be implemented.
[0299] FIG. 209 illustrates a partial view of a computer program
product 20900, in which embodiments may be implemented.
[0300] FIG. 210 illustrates a partial view of the computer program
product of FIG. 209, in which embodiments may be implemented.
[0301] FIG. 211 illustrates a partial view of the computer program
product of FIG. 209, in which embodiments may be implemented.
[0302] FIG. 212 illustrates a partial view of a system 21200, in
which embodiments may be implemented.
[0303] FIG. 213 illustrates a partial view of the system of FIG.
212, in which embodiments may be implemented.
[0304] FIG. 214 illustrates a partial view of the system of FIG.
212, in which embodiments may be implemented.
[0305] FIG. 215 illustrates a partial view of a system 21500, in
which embodiments may be implemented.
[0306] FIG. 216 illustrates a partial view of the system of FIG.
215, in which embodiments may be implemented.
[0307] FIG. 217 illustrates a partial view of the system of FIG.
215, in which embodiments may be implemented.
[0308] FIG. 218 illustrates a partial view of the system of FIG.
215, in which embodiments may be implemented.
DETAILED DESCRIPTION
[0309] In the following detailed description, reference is made to
the accompanying drawings, which form a part hereof. In the
drawings, similar symbols typically identify similar components,
unless context dictates otherwise. The illustrative embodiments
described in the detailed description, drawings, and claims are not
meant to be limiting. Other embodiments can be utilized, and other
changes can be made, without departing from the spirit or scope of
the subject matter presented here.
[0310] In one embodiment, at least one frozen particle composition
(including therapeutic compositions), device, system, product,
machine, or method disclosed herein relates to making,
administering, or utilizing one or more frozen particle
compositions for various purposes.
Frozen Particles
[0311] In one embodiment, the one or more frozen particle
compositions, frozen piercing implements, or frozen piercing
implement devices include one or more frozen particles and
optionally, at least one other agent. In one embodiment, the at
least one agent includes at least one of a therapeutic agent,
reinforcement agent, abrasive, biological remodeling agent,
explosive material, or adhesive agent. In one embodiment, the
frozen particle composition or frozen piercing implement (or
device) includes at least one material that modulates the rate of
diffusion or degradation of the at least one agent. In one
embodiment, the at least one material reduces the rate of diffusion
or degradation of the at least one agent.
[0312] In one embodiment, the at least one agent includes or is
substantially in the form of at least one of an organic or
inorganic small molecule, clathrate or caged compound, protocell,
coacervate, microsphere, Janus particle, proteinoid, laminate,
helical rod, liposome, macroscopic tube, niosome, sphingosome,
toroid, vesicular tube, vesicle, small unilamellar vesicle, large
unilamellar vesicle, large multilamellar vesicle, multivesicular
vesicle, lipid layer, lipid bilayer, micelle, organelle, cell,
membrane, nucleic acid, peptide, polypeptide, protein,
glycopeptide, glycolipid, lipoprotein, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus,
acid, support structure, buffer, protic solvent, aprotic solvent,
nitric oxide, nitrous oxide, nitric oxide synthase, amino acid,
micelle, polymer, copolymer, monomer, prepolymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
nanotube, piloxymer, transfersome, gas, element, contaminant,
radioactive particle, hormone, microorganism, bacteria, virus,
quantum dot, contrast agent, or any part thereof. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements (or devices) include one or more frozen
particles made up of at least one frozen constituent. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements (or devices) include one or more frozen
particles including a single frozen constituent. In one embodiment,
the one or more frozen particles include multiple frozen
constituents. In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements (or devices) include
frozen solute particles, and optionally, at least one agent. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements (or devices) include non-hydrogen oxide frozen
solute particles, and optionally, at least one agent. In one
embodiment, the one or more frozen particle compostions, or frozen
piercing implements (or devices) include frozen solvent particles,
and optionally, at least one agent. In one embodiment, the one or
more frozen particle compositions, or frozen piercing implements
(or devices) include non-hydrogen oxide frozen solvent particles
and optionally, at least one agent. In one embodiment, the one or
more frozen particle compositions, or frozen piercing implements
(or devices) include frozen solution particles, and optionally, at
least one agent. In one embodiment, a frozen particle composition,
or frozen piercing implement (or device) includes one or more
frozen solution particles and at least one agent; wherein the
frozen particle composition is in at least one crystalline or
amorphous phase.
[0313] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements (or devices) include
frozen particles of at least one component that is in a gaseous
state at or above physiological conditions, which include but are
not limited to approximately 0.25 bar, approximately 0.5 bar,
approximately 1.0 bar, approximately 5.0 bar, approximately 10.0
bar, approximately 25 bar, approximately 50 bar, approximately 100
bar, approximately 200 bar, or approximately 500 bar pressure; and
at or above approximately 10.degree. C., approximately 15.degree.
C., approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 35.degree. C.,
approximately 37.degree. C., approximately 40.degree. C.,
approximately 45.degree. C., approximately 50.degree. C.
[0314] In one embodiment, the frozen particle composition, or
frozen piercing implement (or device) includes one or more frozen
particles including at least one of hydrogen oxide, helium, neon,
krypton, argon, xenon, nitrogen, chlorine, bromine, methane,
oxygen, air, carbon dioxide, polyethylene glycol, acetone, ethyl
acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
tetrahydrofuran, acetronitrile, acetic acid, n-butanol,
isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, standard saline citrate, methane, toluene, chloroform,
polyethylene glycol, acetic acid, Ringer's solution, lactated
Ringer's solution, Hartmann's solution, acetated Ringer's solution,
phosphate buffered solution, TRIS-buffered saline solution, Hank's
balanced salt solution, Earle's balanced salt solution, standard
saline citrate, HEPES-buffered saline, dextrose, glucose, methane,
diethyl ether, or any solution, suspension, mixture, or colloid
including one or more thereof.
[0315] In one embodiment, the frozen particle composition, or
frozen piercing implement (or device) includes one or more frozen
solution particles, optionally including at least one agent;
wherein the one or more frozen solution particles have at least one
major dimension of approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer or less, or any value
therebetween.
[0316] In one embodiment, at least one of the constituents of the
one or more frozen particle compositions or frozen piercing
implements (or devices) is frozen. In one embodiment, all of the
constituents of the one or more frozen particle compositions or
frozen piercing implements (or devices) are frozen. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements (or devices) have at least one major dimension
of approximately one decimeter or less, approximately one
centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer
or less, approximately one picometer or less, or any value
therebetween.
[0317] In one embodiment, a plurality of frozen particle
compositions or frozen piercing implements (or devices) is
delivered or administered, and the plurality includes at least two
subsets of frozen particle compositions or frozen piercing
implements which can be differentiated based on size. In one
embodiment, a plurality of frozen particle compositions or frozen
piercing implements includes at least one subset of frozen particle
compositions or frozen piercing implements that have at least one
major dimension of approximately ten micrometers or less. In one
embodiment, the at least one major dimension of the one or more
frozen particle compositions or frozen piercing implements (or
devices) includes at least one of radius, diameter, length, width,
height, or perimeter.
[0318] As described herein, in one embodiment, the one or more
frozen particle compositions or frozen piercing implements
approximate the shape of at least one of a sphere, bullet,
flechette, cone, needle, arrow, spear, diamond, pyramid, cylinder,
mini ball, shuttlecock, spiral, helical, bell, pear, crystal, cube,
spheroid, tetrahedron, crescent, or high aspect ratio shape. The
size, shape, weight, or density, as well as other physical
parameters of the one or more frozen particle compositions or
frozen piercing implements can be adjusted according to a
particular parameter for making or administering the frozen
particle composition, or frozen piercing implement, or desired goal
in utilizing the frozen particle composition(s) or frozen piercing
implement(s). In one embodiment, the one or more frozen particle
compositions or frozen piercing implements include a plurality of
frozen particles that are approximately uniform with regard to
size, shape, weight, or density. In one embodiment, the one or more
frozen particle compositions or frozen piercing implements include
an array of different sizes, shapes, weights, or densities.
[0319] In one embodiment, the frozen particle composition, or
frozen piercing implements is substantially in the form of a
hatchet, saw, rotary device, fork, sciber, graver, spade, screw,
pin, needle, blade, knife, razor, scissors, tweezers, scalpel, or
other tool. In one embodiment, the frozen particle composition, or
frozen piercing implement includes at least one microneedle,
micropin, nanoneedle, or nanopin. In one embodiment, the frozen
particle composition, or frozen piercing implements includes means
for piercing, stitching, extracting material, or administering at
least one agent to at least one substrate.
[0320] In one embodiment, the one or more frozen particle
compositions or frozen piercing implements are substantially solid
at about 30.degree. C., about 20.degree. C., about 10.degree. C.,
about 5.degree. C., about 0.degree. C., about -10.degree. C. about
-20.degree. C., about -30.degree. C., about -40.degree. C., about
-50.degree. C., about -60.degree. C., about -70.degree. C., about
-75.degree. C., about -80.degree. C., about -85.degree. C., about
-90.degree. C., about -95.degree. C., about -100.degree. C., about
-120.degree. C., about -150.degree. C., about -180.degree. C.,
about -200.degree. C., about -220.degree. C., about -250.degree.
C., or any temperature less than or therebetween. In one
embodiment, a frozen piercing implement is substantially solid if
it is approximately 1%, approximately 5%, approximately 10%
approximately 20%, approximately 30%, approximately 40%,
approximately 50%, approximately 60%, approximately 70%,
approximately 80%, approximately 90%, approximately 99%,
approximately 100% solid, or any value therebetween.
[0321] In one embodiment, the frozen particle composition or frozen
piercing implement (or device) includes at least one of a solid,
liquid, or gas. In one embodiment, the frozen particle composition,
or frozen piercing implement (or device) includes at least one of a
frozen liquid, or frozen gas. In one embodiment, the frozen
particle composition or frozen piercing implement (or device)
includes at least one pharmaceutically acceptable carrier or
excipient. In one embodiment, the frozen particle composition, or
frozen piercing implement (or device) is formulated to be
administered by one or more of topical administration, oral
administration, enteral administration, mucosal administration,
percutaneous administration, or parenteral administration. In one
embodiment, parenteral administration includes at least one of
intravenous administration, intra-arterial administration,
intracardiac administration, subcutaneous administration,
intraperitioneal administration, or intramuscular administration.
In one embodiment, the frozen particle composition, or frozen
piercing implement (or device) is formulated to be administered by
high velocity impact. In one embodiment, the frozen particle
composition, or frozen piercing implement (or device) is formulated
to be administered by one or more devices.
[0322] In one embodiment, the at least one frozen particle
composition or frozen piercing impelement at least partially melts
during administration, or upon contact with the substrate (e.g.,
biological cell, tissue, or organ). For example, the frozen
components of the at least one frozen particle composition or
frozen piercing implement will melt or vaporize as a thermal
transfer occurs from the environment or substrate (e.g., biological
cell, tissue, organ, structure, or device) to the composition or
implement. In one example, the heat of a subject's body to which
the frozen particle composition or implement is administered at
least partially melts or vaporizes at least one component of the
composition or implement. In one embodiment, at least part of the
composition or implement does not melt or vaporize (e.g., magnetic
particles, therapeutic agent, sensor, etc.). In one embodiment, the
frozen particle composition or frozen piercing implement acts as a
vehicle for delivering at least one agent (therapeutic agent,
adhesive agent, biological remodeling agent, etc.) or article
(e.g., sensor, detection material, etc.) wherein the vehicle
dissipates upon administration.
[0323] As described herein, in one embodiment, the substrate is
cooled prior to, during, or subsequent to administration of the at
least one frozen particle composition or frozen piercing implement,
which reduces the thermal transfer and allows for a slower melting
or evaporation process to occur. In one embodiment, all of the
constituents of the frozen particle composition or frozen piercing
implement are frozen. In one embodiment, at least one constituent
of the frozen particle composition or frozen piercing implement is
not frozen (e.g., magnetic particle, adhesive agent, sensor,
etc.).
[0324] In one embodiment, the frozen particle composition, or
frozen piercing implement (or device) includes one or more of a
suspension, mixture, solution, sol, clathrate, colloid, emulsion,
microemulsion, aerosol, ointment, capsule, powder, tablet,
suppository, cream, device, paste, resin, liniment, lotion, ampule,
elixir, spray, syrup, tincture, detection material, polymer,
biopolymer, buffer, adjuvant, diluent, lubricant, disintegration
agent, suspending agent, solvent, light-emitting agent,
colorimetric agent, glidant, anti-adherent, anti-static agent,
surfactant, plasticizer, emulsifying agent, flavor, gum, sweetener,
coating, binder, filler, compression aid, encapsulation aid,
preservative, granulation agent, spheronization agent, stabilizer,
adhesive, pigment, sorbent, nanoparticle, or gel.
[0325] In one embodiment, the one or more frozen particles include
one or more frozen hydrogen oxide particles. In one embodiment, the
frozen particle composition, or frozen piercing implement (or
device) includes one or more frozen particles, wherein the frozen
hydrogen oxide particle is in one or more phases including at least
one of amorphous solid water, low density amorphous ice, high
density amorphous ice, very high density amorphous ice, clathrate
ice, hyperquenched glassy water, ice Ic, ice Ih, ice II, ice III,
ice IV, ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI,
ice XII, ice XIII, ice XIV, or ice XV.
[0326] In one embodiment, the one or more frozen particle
compositions, frozen piercing implements (or devices) include
frozen hydrogen oxide particles. Frozen hydrogen oxide, or typical
water ice, exists in several non-crystalline forms. Each of these
forms has specific physical characteristics such as density and
vibrational spectra. Some examples of frozen hydrogen oxide phase
transformations are shown in FIG. 1. (See e.g., Chaplin, the
worldwide web at lsbu.ac.uk/water; Ivanov et al., Russian J. Gen.
Chem. vol. 75, pp. 1851-1856 (2005), each of which is incorporated
herein by reference).
[0327] Hydrogen oxide (water) has many frozen phases (ices),
including crystalline and non-crystalline phases. The crystalline
phases generally have the common structure of having hydrogen bonds
to four neighboring water molecules, such as two hydrogen atoms
near each oxygen atom. Structural data on the known frozen hydrogen
oxide polymorphs are shown in Table I, with two known phases of ice
XI. (See, e.g., Chaplin, Ibid; and Zheligovskaya, et al., Russian
Chem. Rev.75, pp. 57-76, 2006, each of which is incorporated herein
by reference).
TABLE-US-00001 TABLE I Structural Data on the Ice Polymorphs
Dielectric Density, constant, Ice polymorph g/cm.sup.3 Protons
Crystal Symmetry .di-elect cons..sub.S Notes Hexagonal ice, Ih 0.92
disordered Hexagonal One C.sub.6 97.5 Cubic ice, Ic 0.92 disordered
Cubic four C.sub.3 LDA, Ia 0.94 disordered Non- As prepared,
crystalline can be mixtures of several types HAD 1.17 disordered
Non- As prepared, crystalline can be mixtures of several types VHDA
1.25 disordered Non- crystalline II 1.17 ordered Rhombohedral One
C.sub.3 3.66 III 1.14 disordered Tetragonal One C.sub.4 117 protons
can be partially ordered IV 1.27 disordered Rhombohedral One
C.sub.3 metastable in ice V phase space V 1.23 disordered
Monoclinic One C.sub.2 144 protons can be partially ordered VI 1.31
disordered Tetragonal One C.sub.4 193 protons can be partly ordered
VII 1.50 disordered Cubic four C.sub.3 150 two interpenetrating ice
Ic frameworks VIII 1.46 ordered Tetragonal One C.sub.4 4 low
temperature form of ice VII IX 1.16 ordered Tetragonal One C.sub.4
3.74 low temperature form of ice III, metastable in ice II space X
2.51 symmetric Cubic four C.sub.3 symmetric proton form of ice VII
XI 0.92 ordered Orthorhombic three C.sub.2 low temperature form of
ice Ih XI >2.51 symmetric Hexagonal distorted Found in close
packed simulations only XII 1.29 disordered Tetragonal One C.sub.4
metastable in ice V phase space XIII 1.23 ordered Monoclinic One
C.sub.2 ordered form of ice V phase XIV 1.29 mostly Orthorhombic
One C.sub.4 ordered form of ordered ice XII phase XV 1.31 (?)
ordered ? ? ordered form of ice VI phase
[0328] Cooling liquid hydrogen oxide below its standard freezing
point typically results in the formation of frozen hexagonal ice.
However, if the hydrogen oxide is pure and cooled slowly, the
liquid hydrogen oxide can be supercooled to approximately
-42.degree. C. Amorphous solids harden without crystallizing, such
that if hydrogen oxide is cooled rapidly it results in formation of
a glass-like state, for example, hyperquenched glassy water. (See
e.g., Debenedetti, J. Phys. Condens. Matter, vol. 15, pp.
R1669-R1726 (2003), and as cited by Chaplin, worldwideweb at
lsbu.ac.uk/water; each of which is incorporated herein by
reference.) Generally, hyperquenched glassy water is formed by
rapidly spraying a fine mist of micrometer-sized hydrogen oxide
droplets into very cold liquefied gas, such as propane.
Alternatively, a fine mist of hydrogen oxide can be sprayed onto a
very cold frozen cell or tissue, for example, at or below
approximately -193.degree. C. Hyperquenched glassy water may also
be formed by cooling capillary tubes containing bulk liquid water
(.about.100 .mu.m diameter) with liquid helium, for example, at
approximately -269.degree. C. In one embodiment, the frozen
particle composition includes a constitutent in a superglass state,
or supersolid. For example, solid helium includes a supersolid, or
a superglass amorphous solid. See, for example, Hunt, et al.,
Science, vol. 324, pp. 632-635 (2009), which is incorporated herein
by reference.
[0329] As shown in FIGS. 1-4, hydrogen oxide attains various
structures and phases depending upon the temperature or pressure of
the environment. As indicated in FIG. 1, for example, hydrogen
oxide ice Ic is derived from high density amorphous water or deeply
supercooled liquid water, when put under low temperature or higher
pressure. Likewise, as indicated in FIG. 2, the hydrogen oxide has
a greater density as a liquid than as a solid under ambient
conditions (ice Ih). However, at increasing pressure, at least ice
stages III, V, VI, and VII exhibit a greater density than liquid
hydrogen oxide. FIG. 3 indicates the phase diagram for hydrogen
oxide based on pressure and temperature variance, while FIG. 4
shows the specific sub-categories of hydrogen oxide based on
physical properties, such as structure and density, among others,
as the temperature and pressure vary.
[0330] Similarly, amorphous solid water is formed from the slow
deposition of hydrogen oxide vapor on a cold metal crystal surface
(for example, at less than approximately 2 nm/s), below the
temperature of approximately -153.degree. C. Amorphous solid water
is a viscous semi-solid material that has a density of
approximately 0.94 g/cm.sup.3 and harbors gaps and spaces in its
structure, as well as reactive hydrogen bonds. These structures are
removed by annealing under vacuum pressure, which allows the
material to convert to a high density glassy water or low density
amorphous ice, depending on the temperature. Typically, high
density glassy water, which has a density of approximately 1.1
g/cm.sup.3, is formed by vapor deposition at approximately
-263.degree. C.
[0331] Low-density amorphous (LDA) ice also occurs from heating
high-density amorphous (HDA) ice to just above approximately
-153.degree. C. at atmospheric pressure, and transforms to cubic
ice at approximately -113.degree. C. to -123.degree. C. Low-density
amorphous ice is also prepared by submitting low-pressure phases
(Ih, Ic, XI, etc.) to high pressure (e.g., approximately 1.0 GPa)
at low temperatures (e.g., below approximately -148.degree.
C.).
[0332] Very-high density amorphous (VHDA) ice is a viscous water
state with a density of approximately 1.25 g/cm.sup.3, and is
prepared by heating high-density amorphous ice to just above
approximately -113.degree. C. and approximate pressure of 1.15 GPa.
When very-high density amorphous ice is heated at different
pressures between, e.g., 0.3 and 2 GPa, it re-crystallizes into
only the proton disordered ices III, IV, V, XII, VI and VII in
order of increasing pressure, but does not typically re-crystallize
into the proton ordered phases (e.g., ice II).
[0333] Typically, the density of liquid water increases with
increased pressure. When liquid water approaches the critical point
in the liquid-vapor phase, water enters a supercritical phase where
it exists as small but liquid-like hydrogen-bonded clusters
dispersed within a gas-like phase and its physical properties vary
according to changing density. Supercritical water is an excellent
solvent for non-polar molecules, due to its low dielectric constant
and poor hydrogen bonding. Due to these same properties,
supercritical water is typically not a good solvent for
electrolytes, which tend to form ionic bonds.
[0334] As indicated in FIG. 2, hexagonal ice is less dense than
liquid water, whereas the other ice phases are all denser and phase
changes occur near the liquid and solid densities (See e.g.,
Loerting et al., J. Phys.: Condens. Matter vol. 18, R919-R977
(2006), which is incorporated herein by reference). Liquid water
density varies with change in temperature or pressure, whereas the
density of amorphous ice varies only with change in pressure, but
not temperature.
[0335] Hydrogen oxide has a high heat of vaporization
(approximately 40.7 kJ/mol), and a high heat of sublimation
(approximately 51.059 kJ/mol at 0.degree. C.), which allows for the
frozen particle compositions to remain intact for a short time
period during which the particles are delivered to one or more
cells or tissues. These properties further enable the frozen
particle compositions, or frozen piercing implements to serve as
particles for delivery of at least one therapeutic composition to
one or more cells or tissues.
[0336] Frozen particle compositions, or frozen piercing implements
may include a "solid," such as true solids, semi-solids, and
viscous fluid, such as gels, polymers, hydrogels, or sols. Frozen
particle compositions, or frozen piercing implements including one
or more frozen particles may include particles that are at least
partially frozen, or are entirely frozen. Frozen particle
compositions, or frozen piercing implements including one or more
frozen particles may include one or more subset groups of one or
more particles, some of which are entirely frozen and some of which
are at least partially frozen. For example, a frozen particle
composition may be at least about 1% frozen, about 5% frozen, about
10% frozen, about 20% frozen, about 30% frozen, about 40% frozen,
about 50% frozen, about 60% frozen, about 70% frozen, about 80%
frozen, about 90% frozen, about 95% frozen, about 98% frozen, about
99% frozen, about 100% frozen, or any value there between.
[0337] In one embodiment, frozen particle compositions, or frozen
piercing implements may include multiple different constitutions,
wherein a group of frozen particle compositions, or frozen piercing
implements includes at least one subset of multiple frozen
particles, wherein each frozen particle has an individual
therapeutic agent, adhesive agent, biological remodeling agent,
abrasive, explosive material, reinforcement agent, other agent, a
common constitution, or unique constitution. The group of frozen
particle compositions, or frozen piercing implements may also
include at least one subset of multiple frozen particles, wherein
each frozen particle includes multiple agents.
[0338] A particular plurality of frozen particle compositions, or
frozen piercing implements may include multiple frozen particles
where various multiple agents are associated with a single
particle. Likewise, a particular plurality of frozen particle
compositions, or frozen piercing implements may include various
multiple agents, where each individual agent is associated with a
single frozen particle. In one embodiment, a plurality of frozen
particle compositions, or frozen piercing implements includes any
number of subsets of frozen particles associated with a particular
agent, or other constituent. During the course of any particular
method described herein, one or more plurality of frozen particle
compositions, or frozen piercing implements, or any particular
subset thereof, can be administered in a single treatment or in
multiple treatments. A frozen particle composition or frozen
piercing implement including at least one therapeutic agent may be
referred to as a "therapeutic composition" or "frozen particle
therapeutic composition" herein.
[0339] In certain instances, the one or more frozen particle
compositions, or frozen piercing implements are utilized at a very
low temperature, which may increase the degree of penetration of
the one or more particles or the one or more compositions or
implements for a biological tissue. In certain instances, the one
or more frozen particle compositions, or frozen piercing implements
are utilized at higher temperatures, depending on the freezing
temperature of the constituents of the one or more particles, the
goals of administration or treatment, or other factors. For
example, the freezing point of nitrogen is approximately
-210.degree. C., whereas the freezing point of dimethyl sulfoxide
(DMSO) is approximately 18.45.degree. C. In one embodiment, the one
or more frozen particle compositions, or frozen piercing implements
are utilized at room temperature, or physiological temperature.
[0340] Hydrogen oxide becomes more viscous as the temperature is
decreased to below approximately 33.degree. C., or the pressure is
increased. Ice Ic is generally formed by condensation of water
vapor, at ambient pressure and low temperatures (less than
approximately -80.degree. C.), or below approximately -38.degree.
C. as a mist. (See e.g., Murray et al., Phys. Chem. Chem. Phys.
Vol. 8, pp. 186-192 (2006), which is incorporated herein by
reference). Ice Ic is also prepared by reducing the pressure on
high-pressure hydrogen oxide ice at approximately -196.degree. C.
It can be the preferred phase for ice formed from hydrogen oxide
droplets smaller than about 15 nm in radius, particularly at low
temperatures (e.g., -113.degree. C. to -53.degree. C.). (See e.g.,
Johari, J. Chem. Phys. vol. 122 pp. 194504 (2005); Zhang, et al.,
Chem. Phys. Lett. vol. 421, pp. 251-255 (2006), each of which is
incorporated herein by reference).
[0341] Ice Ih constitutes a large portion of naturally-occurring
snow and ice. Since hexagonal ice exhibits changes in the hydrogen
bonding, ice Ih shows anomalous reduction in thermal conductivity
with increasing pressure (as does cubic ice and low-density
amorphous ice). (See e.g., Andersson et al., Phys. Rev. B vol. 65
pp. 140201.1-14201.4 (2002), which is incorporated herein by
reference).
[0342] Ice II maintains a general rhombohedral unit shape, similar
to ice I. The density of ice II is approximately 1.17 g/cm.sup.3.
Ice III maintains a general tetragonal unit shape, with a density
of approximately 1.14 g/cm.sup.3. Ice VI also maintains a general
tetragonal unit shape, with a density of approximately 1.31
g/cm.sup.3. Ice VII is primarily composed of multiple intercalating
ice Ic lattices, and has a density of approximately 1.66
g/cm.sup.3.
[0343] Some non-limiting examples of materials that are included in
one or more compositions, or implements described herein include,
but are not limited to, liquid nitrogen, which is nontoxic and
inert, with a freezing point at 1 atm pressure of approximately
-210.degree. C. Liquid helium is nontoxic and inert, with a
freezing point at 367 psi of approximately -272.2.degree. C. Liquid
argon is nontoxic and inert with a freezing point at 1 atm pressure
of approximately -189.4.degree. C. Liquid neon has a freezing point
of approximately -245.95.degree. C., while liquid xenon has a
freezing point of approximately -111.9.degree. C. The freezing
point of liquid dimethyl sulfoxide (DMSO) is approximately
18.45.degree. C., and water or other co-solvents can decrease the
freezing point. The freezing point of lactated Ringer's solution is
approximately -45.degree. C. These and other materials can be
utilized as described herein either alone, or in combination with
other materials.
[0344] In one embodiment, at least one frozen particle composition,
or frozen piercing implement, is made or maintained by utilizing a
magnetic time-averaged orbiting potential trap. See, for example,
Han et al., Phys. Rev. vol. 57, pp. R4114-4117 (1998), which is
incorporated herein by reference. In one embodiment, the at least
one frozen particle composition includes one or more Bose-Einstein
condensation of a dilute atomic gas. Id.
[0345] In one embodiment, the frozen particle composition, or
frozen piercing implements includes a clathrate. Clathrate ice
forms from water or other liquids, and contains small amounts of
non-polar molecules (generally gases) under moderate pressure of a
few MPa, and temperatures close to 0.degree. C. Clathrate
structures can vary, but generally allow a minimum amount of small
molecules to fit into and stabilize gaps without forming covalent
or hydrogen bonds with the hydrogen oxide molecules. Certain
clathrates are formed at the interface of the liquid phase, under
atmospheric pressure. Clathrates include but are not limited to the
structural forms of sI, sII, and sh. In certain instances, noble
gases can be used to form clathrate compounds with hydrogen oxide
or other molecules. Noble gases generally have low polarizability,
and tend to be spherically symmetrical, which allows for solubility
with the hydrogen oxide cage. In addition, the solubility of the
noble gases increases considerably as the temperature is
lowered.
[0346] The solubility properties of particular noble gases as
clathrates with hydrogen oxide are shown in Table IV. (See e.g.,
Dec et al., J. Solution Chem. vol. 14, pp. 417-429 (1985); Ivanov,
et al., J. Struct. Chem. vol. 46, pp. 253-263 (2005);
Fernandez-Prini, et al., Elsvier, pp. 73-98 (2004); Ivanov, et al.,
Russian J. Gen. Chem. vol. 75, pp. 1851-1856 (2005), each of which
is incorporated herein by reference.)
TABLE-US-00002 TABLE IV Solubility Properties of the Noble Gases
Property He Ne Ar Kr Xe Rn Atomic number 2 10 18 36 54 86 Atomic
radius, .ANG. 1.08 1.21 1.64 1.78 1.96 2.11 .DELTA.G.degree. of
solution in H.sub.2O at 25.degree. C., kJ/mol 29.41 29.03 26.25
24.80 23.42 .DELTA.H.degree. of solution in H.sub.2O at 25.degree.
C., kJ/mol -0.59 -3.80 -11.98 -15.29 -18.99 .DELTA.S.degree. of
solution in H.sub.2O at 25.degree. C., J/molK -100.6 -110.1 -128.2
-134.5 -142.2 Solubility, mM, 5.degree. C., 101,325 Pa H.sub.2O
0.41 0.53 2.11 4.20 8.21 18.83 D.sub.2O 0.49 0.61 2.38 4.61 8.91
20.41 Solubility minima, .degree. C. H.sub.2O 30 50 90 108 110
D.sub.2O 53 53 98 108 116
[0347] In one embodiment, the frozen particle composition, or
frozen piercing implements includes at least two frozen particles
that are joined. In one embodiment, the at least two frozen
particles are joined by at least one agent. In one embodiment, the
at least two frozen particles are joined by at least one cavity or
compartment. In one embodiment, the frozen particle composition, or
frozen piercing implement includes a cluster of three or more
frozen particles that are joined. In one embodiment, the cluster of
three or more frozen particles is joined by at least one agent. In
one embodiment, the cluster of three or more frozen particle is
joined by at least one cavity or compartment.
Cavitized or Compartmentalized Frozen Particle Compositions or
Frozen Piercing Implements
[0348] In one embodiment, the frozen particle composition, or
frozen piercing implement includes at least one frozen particle as
described herein, defining at least one cavity or compartment
configured for holding at least one agent, article or other
material. In one embodiment, the at least one cavity contains at
least one agent. In one embodiment, the frozen particle
composition, or frozen piercing implement includes at least one
frozen particle defining at least one cavity or compartment
containing at least one agent, and further including one or more
agents located outside of the at least one cavity.
[0349] In one embodiment, the frozen particle composition, or
frozen piercing implement includes at least one inlet port in fluid
communication with the at least one cavity. In one embodiment, the
frozen particle composition, or frozen piercing implement includes
at least one status indicator. In one embodiment, the at least one
status indicator indicates one or more of: content of the at least
one cavity, amount of cavity space occupied, or amount of cavity
space available. In one embodiment, the at least one status
indicator includes at least one of a sensor, a magnet, a
colorimetric substance, or a physical measuring device. In one
embodiment, the at least one status indicator measures one or more
of a change in cavity volume, a change in cavity shape, a change in
cavity temperature, a change in cavity pressure, a change in cavity
pH, a change in frozen particle density, a change in frozen
particle volume, a change in frozen particle weight, a change in
frozen particle temperature, a change in frozen particle shape, a
change in electrical field, a change in vehicle magnetic field, a
change in frozen particle pH, a change in the state of an
activatable agent of the composition, or a change in the state of
an activating factor or inactivating factor of the composition.
[0350] In one embodiment, the at least one cavity includes at least
one of a permeable, semi-permeable or impermeable partition. In one
embodiment, the at least one cavity includes at least one of at
least one means for at least partially sealing the cavity. In one
embodiment, the at least one cavity includes at least one cap,
seal, screw, door, or hinge. In one embodiment, the at least one
cavity is substantially in the form of at least one of a
space-filling curve, a depression, a helix, a cylinder, a spheroid,
a cuboid, a high aspect ratio shape, a tetrahedron, a pyramid, a
channel, or a cone.
[0351] In one embodiment, the at least one cavity differs in
physical or chemical composition from at least one other cavity of
the frozen particle. In one embodiment, the cavity or compartment
is configured to physically or chemically separate the at least one
agent from at least one other cavity of the frozen particle
composition, or frozen piercing implement. In one embodiment, the
at least one cavity or compartment is configured to physically or
chemically separate from at least one other cavity or compartment
of the frozen particle composition, or frozen piercing implement
during administration. In one embodiment the frozen particle
composition, or frozen piercing implement includes at least one
agent, and the at least one agent includes at least one agent in a
different phase state than the frozen particle composition. In one
embodiment, the at least one cavity or compartment includes at
least one of a solid, liquid, or gas. In one embodiment, the at
least one cavity or compartment includes at least one of a liquid
or gas, and at least one other cavity or compartment includes a
solid.
[0352] In one embodiment, the at least one cavity or compartment
includes at least one clathrate. In one embodiment, the at least
one cavity or compartment includes at least one matrix. In one
embodiment, the at least one cavity or compartment is an inner core
cavity of at least one frozen particle composition, or frozen
piercing implement. In one embodiment, the at least one cavity or
compartment includes an inner core region and wherein the at least
one agent is at least one of a liquid or gas. In one embodiment,
the at least one cavity or compartment is intercalated with at
least one other cavity or compartment. In one embodiment, the at
least one cavity is located at a substantially superficial or
exterior region of the one or more frozen particle compositions, or
frozen piercing implements. In one embodiment, the at least one
agent is distributed substantially uniformly within the at least
one substantially superficial or exterior region.
[0353] In one embodiment, the at least one cavity or compartment
has a higher concentration of the at least one agent than any other
cavity or compartment. In one embodiment, the at least one cavity
or compartment includes a graduated concentration of the at least
one agent. In one embodiment, the at least one cavity or
compartment includes varying levels of the at least one agent. In
one embodiment, the at least one agent is fractionated. In one
embodiment, the cavity or compartment includes one or more layers
of at least one agent. In one embodiment, the cavity or compartment
includes one or more layers of multiple agents. In one embodiment,
the at least one agent includes one or more of a pro-drug or
precursor compound. In one embodiment, the at least one agent
includes one or more time-release or extended-release formulations.
In one embodiment, the at least one agent includes an activatable
agent. In one embodiment, the at least one agent is configured to
activate upon administration of the frozen particle composition ,
or frozen piercing implement. In one embodiment, the at least one
activatable agent is configured to activate by one or more of an
enzymatic reaction, a reduction reaction, an oxidation reaction, a
reduction-oxidation reaction, a hydrolysis reaction, a dehydration
synthesis reaction, a glycosylation reaction, a phosphorylation
reaction, a dehydration reaction, a hydration reaction, a
decarboxylation reaction, a condensation reaction, a polymerization
reaction, a glycolysis reaction, a gluconeogenesis reaction, a
fermentation reaction, a photo chemical reaction, a thermal
reaction, a magnetic reaction, an electrical reaction, an
electrochemical reaction, a photolysis reaction, a photosynthetic
reaction, an esterification reaction, altering the pressure on at
least one frozen particle composition , or frozen piercing
implement, altering the content of at least one frozen particle
composition, or frozen piercing implement, altering at least one
chemical property of at least one frozen particle composition , or
frozen piercing implement, altering at least one physical property
of at least one frozen particle composition, or frozen piercing
implement , or applying at least one external stimulus to at least
one frozen particle composition, or frozen piercing implements.
[0354] In one embodiment, the at least one external stimulus
includes one or more of light, heat, electrical field, magnetic
field, or electromagnetic energy. In one embodiment, the frozen
particle composition , or frozen piercing implement further
comprises at least one activating factor or at least one
inactivating factor capable of modulating the activity of the at
least one agent. In one embodiment, the at least one activating
factor or the at least one inactivating factor forms at least part
of one or more of a lipid conjugate, carbohydrate conjugate,
peptide conjugate, polymer-lipid conjugate, fusion protein,
antibody or antibody fragment, receptor or receptor fragment,
reversible inhibitor, irreversible inhibitor, enzyme, gene
repressor, gene suppressor, microRNA, siRNA, kinase, gene
activator, DNA-binding protein, polymerase, gene promoter, gene
enhancer, diamagnetic chemical, explosive material, reactive metal,
adhesive agent, abrasive, reinforcement agent, biological
remodeling agent, or therapeutic agent.
[0355] In one embodiment, the at least one activating or
inactivating agent is configured to activate by one or more of
altering the temperature of at least one frozen particle
composition, or frozen piercing implement, altering the pressure on
at least one frozen particle composition, or frozen piercing
implement, altering the content of at least one frozen particle
composition, or frozen piercing implement, altering at least one
electrical property of at least one frozen particle composition, or
frozen piercing implement, altering at least one magnetic property
of at least one frozen particle composition, or frozen piercing
implement, altering at least one chemical property of at least one
frozen particle composition, or frozen piercing implement, altering
at least one physical property of at least one frozen particle
composition, or frozen piercing implement, or applying at least one
external stimulus to at least one frozen particle composition, or
frozen piercing implement.
[0356] In one embodiment, the at least one cavity or compartment is
in substantially in a form that is different than the remainder of
the frozen particle composition, or frozen piercing implement. In
one embodiment, the at least one cavity or compartment is
substantially in the form of at least one of an organic or
inorganic small molecule, clathrate or caged compound, protocell,
coacervate, microsphere, Janus particle, proteinoid, laminate,
helical rod, liposome, macroscopic tube, niosome, sphingosome,
toroid, vesicular tube, vesicle, small unilamellar vesicle, large
unilamellar vesicle, large multilamellar vesicle, multivesicular
vesicle, lipid layer, lipid bilayer, micelle, organelle, cell,
membrane, nucleic acid, peptide, polypeptide, protein,
glycopeptide, glycolipid, lipoprotein, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus,
acid, support structure, buffer, protic solvent, aprotic solvent,
nitric oxide, nitrous oxide, nitric oxide synthase, amino acid,
micelle, polymer, copolymer, monomer, prepolymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
nanotube, piloxymer, transfersome, gas, element, contaminant,
radioactive particle, hormone, microorganism, bacteria, virus,
quantum dot, contrast agent, or any part thereof. In one
embodiment, the agent includes at least one negatively charged
substance. In one embodiment, the agent includes at least one
positively charged substance.
[0357] In one embodiment, a frozen particle composition, or frozen
piercing implement comprises a frozen hydrogen oxide particle
defining two or more cavities, wherein the two or more cavities
each contain at least one agent. In one embodiment, the two or more
cavities each contain at least one different agent. In one
embodiment, the different agents are configured to combine upon
administration of the frozen particle composition, or frozen
piercing implement. In one embodiment, the different agents are
configured to react upon administration of the frozen particle
composition, or frozen piercing implement. In one embodiment, the
different agents are configured to act cooperatively or
synergistically upon administration of the frozen particle
composition, or frozen piercing implement.
[0358] In one embodiment, a frozen particle composition comprises a
frozen particle composition, or frozen piercing implement defining
three or more cavities, wherein the three or more cavities each
contain at least one agent. In one embodiment, a frozen particle
composition, or frozen piercing implement comprises a frozen
particle defining four or more cavities, five or more cavities, six
or more cavities, seven or more cavities, eight or more cavities,
or any value greater than.
Agents
[0359] In one embodiment, the frozen particle composition, or
frozen piercing implement includes at least one agent. In one
embodiment, the frozen particle provides a vehicle for the at least
one agent. In one embodiment, the frozen particle is constituted
solely by the at least one agent. In one embodiment, the agent
includes at least one nontoxic, biocompatible, bioresorbable, or
biodegradable agent. In certain instances, the one or more
reinforcement agents, one or more explosive materials, one or more
abrasives, one or more adhesive agents, or one or more therapeutic
agents, or one or more biological remodeling agents are utilized in
the form of a plate, spheroid, resin, powder, solution, flake,
sheet, film, ribbon, gel, ball, pellet, or bead. (See e.g., U.S.
Pat. No. 5,534,584; U.S. Pat. No. 5,331,046; each of which is
incorporated herein by reference). The one or more materials or
agents of the frozen particle compositions, or frozen piercing
implements can be in the form of a solid, liquid, or gas. In one
embodiment, one or more of the agents are the same agent. For
example, in one embodiment, the frozen particle composition, or
frozen piercing implement includes at least one therapeutic agent
that is the same as a reinforcement agent, an adhesive agent, an
abrasive, an explosive material, or a biological remodeling agent.
In one embodiment, any one single agent is the same as any single
other agent (i.e. the constitution of an agent may be the same as
another agent, or the function of an agent may be the same as
another agent).
[0360] In certain instances, at least one agent may be configured
to provide more than one function. For example, in one embodiment,
the at least one therapeutic agent and the at least one adhesive
agent, biological remodeling agent, abrasive, reinforcement agent,
or explosive material are the same agent. In one embodiment, the at
least one adhesive agent and the at least one biological remodeling
agent, therapeutic agent, abrasive, reinforcement agent, or
explosive material are the same. In one embodiment, the at least
one biological remodeling agent and the at least one adhesive
agent, therapeutic agent, abrasive, reinforcement agent, or
explosive material are the same agent. In one embodiment, the at
least one reinforcement agent and the at least one adhesive agent,
therapeutic agent, biological remodeling agent, abrasive, or
explosive material are the same. In one embodiment, the at least
one abrasive and the at least one adhesive agent, therapeutic
agent, biological remodeling agent, explosive material, or
reinforcement agent are the same. In one embodiment, the at least
one explosive material and abrasive, adhesive agent, therapeutic
agent, biological remodeling agent, or explosive material are the
same.
[0361] In one embodiment, the at least one is included as part of
at least one carrier that assists in synthesis or activation of the
at least one agent. In one embodiment, the at least one carrier
encompasses the at least one agent. In one embodiment, the carrier
includes a microbe, other cell (such as a cell from a subject or
related to a particular subject, including but not limited to a
transgenic cell). In one embodiment, the cellular carrier is
included in the one or more frozen particle compositions, or frozen
piercing implements described. In one embodiment, the carrier
includes or is substantially in the form of at least one of at
least one of an organic or inorganic small molecule, clathrate or
caged compound, protocell, coacervate, microsphere, Janus particle,
proteinoid, laminate, helical rod, liposome, macroscopic tube,
niosome, sphingosome, toroid, vesicular tube, vesicle, small
unilamellar vesicle, large unilamellar vesicle, large multilamellar
vesicle, multivesicular vesicle, lipid layer, lipid bilayer,
micelle, organelle, cell, membrane, nucleic acid, peptide,
polypeptide, protein, glycopeptide, glycolipid, lipoprotein,
sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan,
lipid, carbohydrate, metalloprotein, proteoglycan, chromosome,
nucleus, acid, support structure, buffer, protic solvent, aprotic
solvent, nitric oxide, nitrous oxide, nitric oxide synthase, amino
acid, micelle, polymer, copolymer, monomer, prepolymer, cell
receptor, adhesion molecule, cytokine, chemokine, immunoglobulin,
antibody, antigen, platelet, extracellular matrix, blood, plasma,
cell ligand, zwitterionic material, cationic material,
oligonucleotide, nanotube, piloxymer, transfersome, gas, element,
contaminant, radioactive particle, hormone, microorganism,
bacteria, virus, quantum dot, contrast agent, or any part
thereof.
[0362] In one embodiment, the at least one agent is frozen. In one
embodiment, the at least one agent is at least partially frozen. In
at least one embodiment, the frozen particle composition, or frozen
piercing implement includes one or more frozen particles and at
least one agent that is not frozen. In one embodiment, the at least
one agent includes two or more components configured to combine
upon administration of the at least one agent.
[0363] In one embodiment, the at least one agent includes one or
more inactive components. In one embodiment, the at least one agent
includes two or more components that are configured to activate
when combined. In one embodiment, the at least one agent includes
one or more components that are configured to activate when
administered. In one embodiment, at least two of the one or more
components are included in the same or different frozen particle
composition, or frozen piercing implement. In one embodiment, at
least two of the one or more components each reside in a separate
cavity of the same or a different frozen particle composition, or
frozen piercing implement. In one embodiment, at least one agent is
included as a precursor molecule.
[0364] In one embodiment, at least one agent is configured to be
activated prior to or subsequent to administration. In one
embodiment, at least one agent is configured to be activated after
a prolonged time subsequent to administration. For example, in
cases where the agent is encased or associated with a polymer or
other agent that may insulate one or more reactant or retard the
explosive or decomposition process, the release of the agent can be
delayed. In one embodiment, the frozen particle composition, or
frozen piercing implement includes at least one activatable agent.
In one embodiment, the frozen particle composition, or frozen
piercing implement includes at least one activating agent or at
least one inactivating agent, or both. In one embodiment, the at
least one agent includes two or more components configured to
combine upon deposition. In one embodiment, the at least one agent
includes two or more components configured to react upon
deposition.
[0365] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements including at least one
agent are part of a kit for administration, optionally to at least
one substrate (including at least one biological cell or tissue).
In one embodiment, one or more subsets of frozen particle
compositions, or frozen piercing implements include different
agents or different components of an agent and are administered in
a kit or device wherein one subset is kept separate from another
subset until administration of the frozen particle compositions, or
frozen piercing implements.
Reinforcement Agents
[0366] In one embodiment disclosed herein, one or more
reinforcement agents are included in the frozen particle
composition, or frozen piercing implement. Examples of some
reinforcement agents include, but are not limited to, polyaramid,
vinylester matrix, metal (including but not limited to gold,
silver, copper, zinc, brass, tin, bronze, gallium, sodium,
potassium, tungsten, steel, iron, carbon, aluminum, copper,
platinum, tantalum, rhodium, or alloys thereof), ceramic,
fiberglass, cellulose, broad carbide, aromatic polyamide, nylon,
silk, rayon, acetate, modacrylic, olefin, acrylic polymer or
copolymer, acrylamide polymer or copolymer, polyester, aromatic
polyester, poly-lactic acid, vinyon, saran, spandex, vinalon,
aromatic nylon, vinylidene chloride, modal, polybenzimidazole,
sulfur, lyocell, orlon, zylon, high-performance polyethylene,
polypyridobenzimidazole, vectran, acrylonitrile rubber, glass,
copper, iron, steel, sodium, potassium, calcium, zinc, manganese,
carbon, magnesium, alluvium, sand, sugar, calcite, emery, diamond,
novaculite, pumice, rouge, borazon, corundum, zirconia alumina,
silicon, silica, frozen hydrogen oxide ice, plant matter, animal
matter, or mineral matter. In one embodiment, plant matter may
include vegetable matter, nuts or nut products or pieces (e.g.,
almonds), grains (e.g., oatmeal), wood (e.g., wood fibers) or other
stalk material, leaf matter, fruit matter (including pits or seeds
or parts thereof), and other plant material.
[0367] In one embodiment, one or more reinforcement agents are made
by spinning into a fiber, wire, or filament. Some non-limiting
examples of reinforcement fibers can be found at, for example, U.S.
Pat. No. 5,855,663; U.S. Pat. No. 5,652,058; KEVLAR.RTM. technical
guide, Polymer Bulletin, vol. 16, pp. 167-174 (1986), and
WO12003/060002, each of which is incorporated herein by
reference.
[0368] The one or more agents are positioned on or in the one or
more frozen particle compositions depending on a given context. For
example, the positioning of one or more agents may consider the
particular goal of administering the one or more frozen particle
compositions, or frozen piercing implements, the components of the
at least one frozen particle composition, or frozen piercing
implement, or the needs or desires of a particular outcome of
treatment or administration of the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
one or more agents are located at least on the surface or beneath
the surface of the one or more frozen particle compositions, or
frozen piercing implements. In one embodiment, the one or more
agents are located within the one or more frozen particle
compositions, or frozen piercing implements.
[0369] As shown in published FIGS. 5 and 6, the strength of
hydrogen oxide ice samples increases when particular reinforcement
agents are added, according to the published studies. As indicated
in published FIG. 5, ice samples exhibit increased strength, as
measured by beam deflection as an angle of shear when reinforced
with fiberglass or kaolin. (See e.g., Kingery, Science, vol. 134,
pp. 164-168 (1960), which is incorporated herein by reference). As
indicated in FIG. 6, the maximum stress (in MPa) and strain rate
increases when particular reinforcement agents are added to the
hydrogen oxide ice samples, according to the published studies.
(See e.g., Yasui et al, Geophys. Res. Lett., vol. 35, L12206,
(2008), which is incorporated herein by reference).
Abrasives
[0370] In certain instances, the frozen particle composition or
frozen piercing implement described herein includes one or more
abrasives. The one or more abrasives may include treated or
untreated abrasives, coated abrasives, bonded abrasives, powders,
aggregates, composites, or other forms. In one embodiment, the one
or more abrasives include, but are not limited to, polyaramid,
vinylester matrix, metal, ceramic, fiberglass, cellulose, broad
carbide, aromatic polyamide, nylon, silk, rayon, acetate,
modacrylic, olefin, acrylic polymer or copolymer, acrylamide
polymer or copolymer, polyester, aromatic polyester, poly-lactic
acid, vinyon, saran, spandex, vinalon, aromatic nylon, vinylidene
chloride, modal, polybenzimidazole, sulfur, lyocell, orlon, zylon,
high-performance polyethylene, polypyridobenzimidazole, vectran,
acrylonitrile rubber, glass, copper, iron, steel, sodium,
potassium, calcium, zinc, manganese, carbon, magnesium, alluvium,
sand, sugar, calcite, emery, diamond, novaculite, pumice, rouge,
borazon, corundum, zirconia alumina, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral matter.
In one embodiment, plant matter may include vegetable matter, nuts
or nut products or pieces (e.g., almonds), grains (e.g., oatmeal),
wood (e.g., wood fibers) or other stalk material, leaf matter,
fruit matter (including pits or seeds or parts thereof), or other
plant material. In one embodiment, the abrasive includes at least
one depilatory.
Explosive Materials
[0371] In one embodiment, one or more frozen particle compositions,
or frozen piercing implements include one or more explosive
materials. Explosive materials are typically chemically or
energetically unstable or produce a sudden expansion of the
material with a change in pressure. Such a sudden expansion of the
material under pressure changes is generally accompanied by the
production of heat. Explosive materials are generally
differentiated according to their decomposition rates. Generally, a
chemical decomposition rate of an explosive material takes about
one or more years, about one or more days, about one or more hours,
about one or more minutes, about one or more seconds, or about a
fraction of a second. Certain explosive materials are relatively
stable, and may maintain their explosive ability for some amount of
time. Other explosive materials have relatively high rates of
decomposition and detonate rapidly.
[0372] In one embodiment, frozen particle compositions, or frozen
piercing implements include one or more explosive materials that
may include, for example, at least one of a high explosive or a low
explosive. In one embodiment, the one or more explosive materials
include at least one of carbonate, carbon dioxide, nitroglycerine,
acid, base, epoxy, acrylic polymer or copolymer, acrlyamide polymer
or copolymer, urethane, hypoxyapatite, or a reactive metal. In
certain instances, the one or more explosive properties are the
result of activation of one or more explosive materials.
[0373] In certain instances, the one or more explosive properties
are the result of inherent tendencies of the frozen particle
compositions, or frozen piercing implements themselves. In certain
instances, the one or more explosive properties relate to an
external event or stimulus, such as a change in temperature or
pressure. In certain instances, the one or more explosive
properties relate to a change in light intensity. In certain
instances, the one or more explosive properties relate to a change
in the composition upon administration or contact with at least one
composition, cell, tissue, or subject. In certain instances, the
one or more explosive properties result from a temperature or
pressure increase relating to penetration of at least one cell,
tissue, or subject. In certain instances, the one or more explosive
properties result from contact with water or other moisture in a
cell or tissue. In certain instances, the one or more explosive
properties result from contact with at least one substrate. In
addition to the intensity of the one or more explosives, the one or
more explosive materials may differ with regard to the volatility,
density, toxicity, hygroscopicity, or brisance of a particular
explosive material.
[0374] Explosive materials may contain at least one oxidizer that
provides fuel for certain explosive materials. In certain
instances, the oxidizer can be an oxidizing element, such as
oxygen. In certain instances, the oxidizer reacts with a reactive
metal; an example of such a compound includes reacting fine metal
powder (e.g., aluminum or magnesium) with an oxidizer (e.g.,
potassium chlorate or perchlorate). Chemically pure compounds may
have high decomposition rates and lead to an explosion, including
but not limited to nitroglycerin, acetone peroxide,
trinitrotoluene, nitrocellulose, carbon, carbon monoxide, chlorine,
potassium nitrate, sulfur, nitrogen compounds (such as nitrite,
nitrate, and azide), potassium chlorate and potassium nitrate,
hydrogen, ammonium nitrate, phosphorous, dinitrogen tetroxide, or
others. In one embodiment, one or more mixtures of organic
materials and oxidizers are included. In one embodiment, one or
more mixtures of reactive metals and oxidizers or oils are
included.
[0375] In one embodiment, the one or more explosive materials
include carbon dioxide gas. In one embodiment, carbon dioxide gas
is entrapped in the frozen particle composition. One method of
incorporating carbon dioxide gas into at least one frozen particle
composition, or frozen piercing implement includes liquefying the
frozen particle composition, or frozen piercing implement and
introducing carbon dioxide gas while maintaining the mixture under
pressure. (See e.g., U.S. Pat. Nos. 4,289,794; 4,289,790;
4,262,029; 5,439,698, each of which is incorporated herein by
reference). The carbon dioxide may also be present as a clathrate
compound.
[0376] In one embodiment, at least one gasified frozen particle
composition, or frozen piercing implement is formed, for example,
by contacting fluid with gas under high pressure for a sufficient
time period to form a gas hydrate. This gas hydrate is then cooled
to a lower temperature in order to freeze the remaining unreacted
fluid and entrap the gas hydrate. As one non-limiting example,
aqueous liquid and carbon dioxide are kept in contact at
approximately 0.degree. C. for a time sufficient under a pressure
range including at least approximately 200 psig to approximately
600 psig, while permitting absorption in the liquid of the gas in
bound form and formation of the gasified ice. This process yields
approximately 25-27.5 milliliters of gas per gram of ice. (See
e.g., U.S. Pat. Nos. 4,487,023; 2,975,603; 3,086,370; 3,217,503,
and 4,404,807, each of which is incorporated herein by
reference).
[0377] Similarly, as described in U.S. Pat. No. 2,975,603, which is
incorporated herein by reference, water contacted with carbon
dioxide at a pressure of approximately 400 psig, in a temperature
bath of approximately 0.degree. C., is subsequently placed at
-10.degree. C. for 24 hours to effect degasification. As described
in U.S. Pat. No. 2,975,603, the resulting product yields
approximately 75 volumes of carbon dioxide per gram of ice.
Additionally, as described in U.S. Pat. No. 3,086,370, which is
incorporated herein by reference, gasified ice products are
produced in a similar manner that contain other gases, such as
nitrous oxide, sulfur-containing gases, chlorine-containing gases,
inert gases, or carbon monoxide.
[0378] In one embodiment, the one or more explosive materials
include at least one of sodium bicarbonate, citric acid, or both.
In one embodiment, the one or more explosive materials include
hydrogen peroxide.
[0379] In certain instances, the at least one frozen particle
composition, or frozen piercing implement is configured to explode
during or upon administration. In certain instances, the at least
one frozen particle composition, or frozen piercing implement is
configured to explode prior to or subsequent to administration. In
certain instances, the at least one frozen particle composition, or
frozen piercing implement explodes after a prolonged time
subsequent to administration or delivery to at least one biological
tissue, or other substrate. For example, in one embodiment, the one
or more explosive materials are encased or associated with a
polymer or other agent that may insulate one or more reactant or
retard the explosive or decomposition process.
Therapeutic Agents
[0380] In one embodiment, the at least one frozen particle
composition, or frozen piercing implement includes at least one
therapeutic agent. (See, e.g., The Merck Index, 14.sup.th Ed. Merck
& Co., Inc., Whitehouse Station, N.J. (2006), which is
incorporated herein by reference). Other therapeutic agents that
are approved for use in humans can be utilized as at least one
therapeutic agent described herein, and can be found at the U.S.
Food and Drug Administration website on the worldwide web at
fda.gov, the information at which is incorporated herein by
reference.
[0381] In certain instances, the one or more frozen particles
themselves provide at least one therapeutic benefit. In certain
instances, the one or more frozen particles act as vehicles for one
or more therapeutic agents that provide at least one therapeutic
benefit. In one embodiment, the one or more frozen particles
including at least one therapeutic agent is inert.
[0382] In one embodiment, the at least one therapeutic agent
includes at least one of an anti-tumor agent, antimicrobial agent,
anti-coagulant, anti-viral agent, analgesic, antiseptic,
anesthetic, diagnostic agent, anti-inflammatory agent, vaccine,
cell growth inhibitor, cell growth promoter, chemical debridement
agent, immunogen, antigen, radioactive agent, apoptosis promoting
factor, angiogenic factor, anti-angiogenic factor, hormone,
enzymatic factor, enzyme, papain, collagenase, protease, peptidase,
elastase, urea, vitamin, mineral, nitrite, nitrate, nutraceutical,
histatin, honey, alcium alginate, angiogenic factor, hormone,
vitamin, mineral, nutraceutical, cytokine, chemokine, probiotic,
sterol, contraceptive, coagulant, anti-coagulant, phage, prodrug,
prebiotic, blood sugar stabilizer, smooth muscle cell activator,
epinephrine, adrenaline, neurotoxin, neuro-muscular toxin,
Botulinum toxin type A, microbial cell or component thereof, or
virus or component thereof. In one embodiment, the nutraceutical
includes one or more of a flavonoid, antioxidant, beta-carotene,
anthocyanin, alpha-linolenic acid, omega-3 fatty acids, yeast,
bacteria, algae, other microorganisms, plant products, or animal
products. In one embodiment, the analgesic or anesthetic includes
one or more of any aminoamid or aminoester local anesthetic,
ibuprofen, morphine, codeine, aspirin, acetaminophen,
lidocaine/lignocaine, ropivacaine, mepivacaine, benzocaine,
chloroprocaine, cocaine, cyclomethycaine, dimethocaine/larocaine,
propoxycaine, procaine/novocaine, proparacaine,
tetracaine/amethocaine, articaine, bupivacaine, carticaine,
cinchocaine/dibucaine, etidocaine, levobupivacaine, piperocaine,
prilocalne, trimecaine, saxitoxin, or tetrodotoxin.
[0383] In one embodiment, the therapeutic agent includes at least
one anti-inflammatory agent, including but not limited to steroids
(e.g., betamethasone, hydrocortisone, and derivatives thereof),
non-steroidal anti-inflammatory drugs, topical anti-inflammatory
agents, or subcutaneously administered non-steroidal
anti-inflammatory drugs (e.g. diclofenac). In one embodiment, the
therapeutic agent includes one or more of: anti-freeze substances
(e.g., polyethylene glycol), antisporiasis agents (e.g., dovonex,
tazarotene, tars, etc.), pigments (e.g., dihyroxyacetone, melanin,
hemoglobin, hemosiderin, iron copper, etc.), depigmenters (e.g.,
hydroquinone, phenolic compounds, etc.), tattoo colorants (e.g.,
skin dyes), preservatives (e.g., benzoate, paraben, or salicylate
compounds), antioxidants (e.g., conezyme Q, vitamins, etc.),
anesthetics (e.g., xylocalne, bupivicane, carbocane, amid or
ester-based anesthetics, etc.), vasoconstrictors (e.g.,
epinephrine, ephedrine, or congeners thereof, etc.), acids (e.g.,
alpha-hydroxy acid, beta-hydroxy acid, halogenated acetic acid,
etc.), irritants (e.g., acids, bases, croton oil, soap, salts of
fatty acids, etc.), antibiotics (e.g., penicillin, amoxicillin,
erythromyc in, tetracycline, monocycline, minocycline, mupirocin,
flagyl, ciprofloxacin, polymixin, gentamycin, etc.), antivirals
(e.g., acyclovir, famciclovir, valtrex, etc.), antifungals (e.g.,
imidazole, nystatin, griseofulvin, sporonox, etc.), depilatories
(e.g., eflornithine hydrochloride), proanthrocyanins (e.g.,
maritime pine extract, tocopheryl acetate, etc.), or other
substances utilized for diagnostic, prophylactic, or treatment of
afflicting conditions.
[0384] In one embodiment, the analgesic includes but is not limited
to one or more of paracetamol (acetaminophen), non-steroidal
anti-inflammatory drugs (NSAIDs), salicylates, narcotics, or
tramadol. In one embodiment, the analgesic includes but is not
limited to aspirin, rofecoxib, celecoxib, morphine, codeine,
oxycodone, hydrocodone, diamorphine, pethidine, buprenorphine,
amitriptyline, carbamazepine, bagapentin, pregabalin, ibuprofen,
naproxen, lidocaine, a psychotropic agent, orphenadrine,
cyclobenzaprine, scopolamine, atropine, gabapentin, methadone,
ketobemidone, or piritramide.
[0385] In one embodiment, the at least one therapeutic agent
includes one or more antiseptic, including but not limited to one
or more of an alcohol, a quaternary ammonium compound, boric acid,
hydrogen peroxide, chlorhexidine gluconate, iodine, mercurochrome,
octenidine dihydrochloride, phenol (carbolic acid) compounds,
sodium chloride, superoxidized water, superoxidized solution,
oxidative reductive potential solution, or sodium hypochlorite.
[0386] In one embodiment, the antiseptic includes but is not
limited to one or more of povidone-iodine, iodine, ethanol,
1-propanol, 2-propanol/isopropanol, benzalkonium chloride, cetyl
trimethylammonium bromide, cetylpyridinium chloride, benzethonium
chloride, chlorhexidine, octenidine dihydrochloride, or carbolic
acid.
[0387] In one embodiment, the at least one therapeutic agent is an
antimicrobial agent, and includes at least one of an anti-fungal
agent, antibiotic agent, anti-bacterial, anti-parasitic agent, or
anti-worm agent. In certain instances, the antimicrobial agent may
occur in nature, or it can be synthetic.
[0388] In one embodiment, the at least one therapeutic agent
includes one or more of a penicillin, cephalosporin, polymixin,
sulfonamide, beta-lactam antibiotic, beta-lactamase inhibitor,
enediynes, lincosamide antibiotic, nitroimidazole antibiotic,
pleuromutilin antibiotic, polyketide antibiotic, polymyxin
antibiotic, polypeptide antibiotic, antimicrobial peptides,
quinolone antibiotic, rifamycin antibiotic, sulfonamide antibiotic,
tetracycline antibiotic, aminoglycoside antibiotic, macrolide,
tetracycline, cyclic lipopeptide, glycylcycline, or oxazolidinone.
In one embodiment, the at least one therapeutic agent includes one
or more of amoxicillin, tobramycin, levofloxacin, gatifloxacin,
moxifloxacin, streptomycin, oxytetracycline, chloramphenicol, or
ampicillin.
[0389] In one embodiment, the at least one therapeutic agent
includes one or more anti-tumor agent, at least one of which may
also be identified as a cytotoxic agent, or chemotherapy agent.
Non-limiting examples of an anti-tumor agent for use as described
herein include at least one of an alkylating agent, antimetabolite,
anthracycline, plant alkaloid (such as paclitaxel), topoisomerase
inhibitor, monoclonal antibody, or tyrosine kinase inhibitor. In
one embodiment, the therapeutic agent includes one or more of
imatinib, mechlorethamine, cyclophosphamide, chlorambucil,
azathioprine, mercaptopurine, vinca alkaloid, taxane, vincristine,
vinblastine, vinorelbine, vindesine, podophyllotoxin, etoposide,
teniposide, amsacrine, dactinomycin, trastuzumab, cetuximab,
rituximab, bevacizumab, dexamethasone, finasteride, tamoxifen,
goserelin, telomerase inhibitor, dichloroacetate, aminopterin,
methotrexate, pemetrexed, raltitrexed, cladribine, clofarabine,
fludarabine, pentostatin, thioguanine, cytarabine, decitabine,
fluorouracil/capecitabine, floxuridine, gemcitabine, enocitabine,
sapacitabine, chloromethine, cyclophosphamide, ifosfamide,
melphalan, bendamustine, trofosfamide, uramustine, carmustine,
fotemustine, lomustine, nimustine, prednimustine, ranimustine,
semustine, spretpozocin, carboplatin, cisplatin, nedaplatin,
oxaliplatin, triplatin tetranitrate, satraplatin, busulfan,
mannosulfan, treosulfan, procarbazine, decarbazine, temozolomide,
carboquone, ThioTEPA, triaziquone, triethylenemelamine, docetaxel,
larotaxel, ortataxel, tesetaxel, vinflunine, ixabepilone,
aclarubicin, daunorubicin, doxorubicin, epirubicin, idarubicin,
amrubicin, pirarubicin, valrubicin, zorubicin, metoxantrone,
pixantrone, actinomycin, bleomycin, mitomycin, plicamycin,
hydroxyurea, camptothecin, topotecan, irinotecan, rubitecan,
belotecan, altretamine, amsacrine, bexarotene, estramustine,
irofulven, trabectedin, cetuximab, panitumumab, trastuzumab,
rituximab, tositumomab, alemtuzumab, bevacizumab, edrecolomab,
gemtuzumab, axitinib, bosutinib, cediranib, dasatinib, erlotinib,
gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib,
sorafenib, sunitinib, vandetanib, alvocidib, seliciclib,
aflibercept, denileukin diftitox, aminolevulnic acid, efaproxiral,
porfimer sodium, talaporfin, temoporfin, verteporfin, alitretinoin,
tretinoin, anagrelide, arsenic trioxide, asparaginase/pegaspergase,
atrasentan, bortezomib, carmofur, celecoxib, demecolcine,
elesclomol, elasamitrucin, etoglucid, lonidamine, lucanthone,
masoprocol, mitobronitol, mitoguanzone, mitotane, oblimersen,
omacetaxine, sitimagene ceradenovec, tegafur, testolactone,
tiazofurine, tipifarnib, or vorinostat.
[0390] In one embodiment, at least one nutraceutical is included.
At least one nutraceutical includes but is not limited to, one or
more of an extract of plant or animal matter (e.g., an oil,
aqueous, or solid extract), a vitamin, a mineral, a mixture or
solution, a food supplement, a food additive, a food fortification
element, or other nutraceutical. In one embodiment, at least one
nutraceutical includes but is not limited to resveratrol, an
antioxidant, psyllium, sulforaphane, isoflavonoid, alpha-linolenic
acid, beta-carotene, anthocyanins, phytoestrogens, polyphenols,
polyphenons, catechins, benzenediols, tannins, phenylpropanoids,
caffeine, alcohol, or others.
[0391] In one embodiment, at least one therapeutic agent includes
one or more vaccine or other prophylactic therapy. In one
embodiment, the therapeutic agent includes a diagnostic agent. In
one embodiment, the frozen particle composition, or frozen piercing
implement including at least one vaccine includes at least one
prophylactic vaccine or therapeutic vaccine. In one embodiment, the
at least one therapeutic vaccine includes at least one anti-cancer
vaccine. In one embodiment, the at least one vaccine includes at
least one of a tumor antigen, microbial antigen, viral antigen,
immunogen, antigen, live microbe, dead microbe, attenuated microbe,
microbe or component thereof, live virus, recombinant virus, killed
virus, attenuated virus, virus component, plasmid DNA, nucleic
acid, amino acid, peptide, protein, glycopeptide, proteoglycan,
glycoprotein, glycolipid, sphingolipid, glycosphingolipid, cancer
cell or component thereof, organic or inorganic small molecule, or
toxoid.
[0392] One or more vaccine may include but not be limited to,
vaccines containing killed microorganisms (such as vaccines for
flu, cholera, bubonic plague, and hepatitis A), vaccines containing
live, attenuated virus or other microorganisms (such as vaccines
for yellow fever, measles, rubella, and mumps), live vaccine (such
as vaccines for tuberculosis), toxoid (such as vaccines for
tetanus, diphtheria, and crotalis atrox), subunit of inactivated or
attenuated microorganisms (such as vaccines for HBV, VLP, and HPV),
conjugate vaccines (such as vaccines for H. influenzae type B),
recombinant vector, DNA vaccination. In one embodiment, the at
least one vaccine includes but is not limited to rubella, polio,
measles, mumps, chickenpox, typhoid, shingles, hepatitis A,
hepatitis B, diphtheria, pertussis, rotavirus, influenza,
meningococcal disease, pneumonia, tetanus, rattlesnake venom,
virus-like particle, or human papillomavirus, or anti-cancer
vaccine.
[0393] In one embodiment, the at least one therapeutic agent
includes at least one adjuvant. The at least one adjuvant may
include but not be limited to one or more organic or inorganic
compounds. The at least one adjuvant may include but not be limited
to at least one of a liposome, virosome, lipid, phospholipid,
mineral salt, single-stranded stranded DNA, double-stranded RNA,
aluminum salts, microbial components carrying pathogen-associated
molecular patterns (e.g., Toll-like receptor ligands or agonists),
lipopolysaccharide, molecular antigen cage, CpG motif (e.g., CPG
oligodeoxynucleotides), microbial cell wall or component thereof,
squalene, oil emulsion, surfactant, saponin, isolated microbial
toxin, modified microbial toxin, endogenous immunomodulator, or
cytokine. In one embodiment, the at least one adjuvant and the at
least one vaccine are located in at least one of the same cavities
of the same frozen particle composition. In one embodiment, the at
least one adjuvant and the at least one vaccine are located in
different cavities of the same frozen particle composition, or
frozen piercing implement. In one embodiment, two or more frozen
particle compositions, or frozen piercing implements of a plurality
of frozen particle compositions, or frozen piercing implements
include one or more similar vaccines. In one embodiment, two or
more frozen particle compositions, or frozen piercing implements of
a plurality of frozen particle compositions, or frozen piercing
implements include one or more dissimilar vaccines.
[0394] In one non-limiting example, a composition includes one or
more frozen particle compositions, or frozen piercing implements
including paclitaxel and at least one other constituent including
at least one frozen component including air, oxygen, nitrogen,
carbon dioxide, hydrogen oxide, helium, neon, xenon, krypton,
chlorine, bromine, methane, or argon.
[0395] In one non-limiting embodiment, a composition or implement
includes one or more frozen particles including one or more
pegylated cytokines or one or more anti-tumor compounds; wherein
the one or more frozen particles include nitrogen, air, oxygen,
carbon dioxide, hydrogen oxide, helium, xenon, krypton, chlorine,
bromine, methane, or argon.
Adhesive Agents
[0396] In one embodiment, at least one adhesive agent is included
in one or more frozen particle compositions, or frozen piercing
implements. In one embodiment, the at least one adhesive agent
includes at least one monomer, prepolymer, polymer, or copolymer.
In one embodiment, the at least one adhesive agent includes at
least one monomer of self-polymerizing agent. In one embodiment,
the at least one adhesive agent is configured to polymerize upon
administration to at least one substrate. In one embodiment, the at
least one adhesive agent is configured to polymerize at or above
the temperature of the at least one substrate. In one embodiment,
the at least one adhesive agent is configured to polymerize at or
above the temperature of at least one biological tissue. In one
embodiment, the at least one adhesive agent is configured to
polymerize at or above the temperature of at least one subject.
[0397] In one embodiment, the at least one adhesive agent includes
one or more of a cement, glue, paste, fixative, or bonding agent.
In one embodiment, the at least one adhesive agent includes one or
more of a solid, liquid, or gas.
[0398] In one embodiment, the at least one adhesive agent is at
least one of non-toxic, biocompatible, biodegradable or
bioresorbable. In one embodiment, the at least one adhesive agent
resists biodegradation or bioresorption. In one embodiment, the at
least one adhesive agent is not biocompatible, or may induce a
response from the at least one biological tissue, or subject's
body. In one non-limiting example, one or more frozen particle
compositions, or frozen piercing implements are administered with
or contain at least one therapeutic agent, such as a vaccine, and
optionally, at least one adhesive agent (which may act as an
adjuvant).
[0399] In one embodiment, the at least one adhesive agent is
degradable or resorbable (e.g., dissolvable sutures constructed
from or secured with an adhesive). See e.g., Sierra, and Saltz,
"Surgical Adhesives and Sealants," Technomic Pub. Co., 1996, which
is incorporated herein by reference. In one embodiment, the at
least one adhesive agent stimulates cell or tissue growth, allowing
for healing of a wound (e.g., burn, surgery incision, etc.) while
the adhesive agent itself subsequently degrades, dissolves, or is
resorbed by the at least one substrate, including at least one
biological tissue or the subject's body. In one embodiment, the at
least one adhesive agent stimulates or increases tissue
regeneration. In one embodiment, the at least one adhesive agent
suppresses or decreases scarring or keloid formation or
recurrence.
[0400] In one embodiment, one or more frozen particle compositions,
or frozen piercing implements include at least one liquid adhesive
agent. For example, the freezing point of acrylic or epoxy resins
is generally approximately -10.degree. C. to -15.degree. C., while
the freezing point of hydrogen oxide water is approximately
0.degree. C. Thus, in one embodiment, one or more frozen hydrogen
oxide particle compositions, or frozen hydrogen oxide piercing
implements include at least one liquid adhesive agent.
[0401] In one embodiment, the at least one adhesive agent includes
one or more of a hemostat, such as a mechanical hemostat (including
but not limited to, porcine gelatin, bovine gelatin, oxidized
regenerated cellulose, or polysaccharide spheres), an active
hemostat (including but not limited to, bovine thrombin, human
pooled thrombin, or recombinant thrombin), a flowable hemostat
(including but not limited to, bovine gelatin and human thrombin,
or porcine gelatin with or without thrombin), or a hemostat and
sealant (such as fibrin sealants of human pooled fibrin; human
fibrin; plasma, collagen, and bovine thrombin; animal fibrin or
thrombin, or others). In one embodiment, the adhesive agent
includes one or more of a sealant (such as polyethylene glycol
(PEG) polymers, including dual PEG or single PEG). In one
embodiment, the adhesive agent includes but is not limited to
albumin (such as bovine serum albumin) and glutaraldehyde. (See,
for example, Spotnitz and Burks, Transfusion, pp. 1502-1516, Vol.
48, 2008; which is incorporated herein by reference.) In one
embodiment, the adhesive agent is part of one or more adhesive
laminates which include at least one adhesive agent and at least
one non-adherent substance (which may optionally be biocompatible,
bioresorbable, biodegradable, or nontoxic). See, for example, U.S.
Patent Application Publication No. 20050153090, which is
incorporated herein by reference.
[0402] In one embodiment, the at least one adhesive agent includes
at least one naturally-occurring substance, such as gelatin, blood
plasma, albumin, collagen, fibrin, fibrinogen (including lytic
fragments, for example FPA, FPB, fragments D and E), hyaluronate,
hyaluronan, glycosaminoglycans, chitin, thrombin, Factor XIII, or
other substances. In one embodiment, the at least one adhesive
agent includes at least one artificial or synthetic substance, such
as an acrylic polymer or copolymer, acrylamide polymer or
copolymer, polyacrylic acid (including but not limited to zinc
polycarboxylate, resin bonding, or glass ionomer cement), epoxy,
urethane, gum arabic, polyester, polyhydroxyalkanoate,
poly(L-lactic acid), polyglycolide, polylactic acid, polyether,
polyol, polyvinylpyrrolidone, pyroxylin,
polymethyacrylate-isobutene-monoisopropylmaleate, siloxane polymer,
polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly(e-caprolactone), sialyl
Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, polyelectrolyte, maleic polyelectrolyte, cellulose,
resilin, cyanoacrylate, isocyanate, (including but not limited to
2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate, monomeric
n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl
2-cyanoacrylate, or its higher homologs (ethyl, butyl, octyl,
etc.), or polyisohexylcyanoacrylate), fibrin, thrombin,
firbrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk,
nylon, collagen, glycosaminoglycan, selectin, polyurethane,
methacrylate, polysulfide, polyanhydride, polydioxanone,
poly-p-dioxanone, albumin, glutaraldehyde, polyethylene glycol,
hydrogel, soy or other plant based adhesives, or gelatin. In at
least one embodiment, the adhesive agent includes gecko glue. In at
least one embodiment, the adhesive agent includes microscopic seta
configured to adhere by van der Waals forces.
[0403] In one embodiment, the at least one adhesive agent includes
one or more of a globin, hemoglobin, heme group, carbohydrate, cell
or cell component, silicone, hydroxyapatite, acrylic polymer or
copolymer, acrylamide polymer or copolymer, hyaluronate or
hyaluronic acid, carboxymethylcellulose, healon, polymer or
biopolymer, gelatin-resorcinol-formaldehyde (GRF) combination, a
fibrin-collagen combination, or a fibrinogen-thrombin combination.
In one embodiment, the at least one adhesive agent includes one or
more naturally-occurring, artificial, or synthetic polymers,
including but not limited to urethane prepolymers or polymers,
cyano-based polymers, polyether, polyol, polyvinylpyrrolidone,
pyroxylin/nitrocellulose,
polymethylacrylate-isobutene-monoisopropylmaleate, acrylate
polymers or siloxane polymers (such as acrylate terpolymer,
polyphenylmethylsiloxane, hexamethyldisiloxane or isooctane solvent
based polymers). (For other specific examples of adhesive agents
see, e.g., U.S. Pat. Nos. 4,740,534 and 7,264,823; and U.S. Patent
Application Nos. 20040097990, 20070161109, and 20070031474, each of
which is incorporated herein by reference). In one embodiment, the
at least one adhesive agent includes a combination of more than one
adhesive agents.
[0404] In one embodiment, the at least one adhesive agent includes
at least one crosslinking or derivatized agent. In one embodiment,
the at least one adhesive agent is configured to form a crosslink
bond with at least one component of at least one substrate. In one
embodiment the crosslink bond of the at least one adhesive agent is
configured for modulation by one or more of a chemical agent,
change in pH, change in exposure to air, vacuum, change in moisture
content, change in pressure, or change in temperature. In one
embodiment, the formation of a crosslink bond of the at least one
adhesive agent is configured for modulation by exposure of the at
least one adhesive agent to one or more of electromagnetic energy,
optical energy, thermal energy, laser energy, ionizing radiation,
non-ionizing radiation, or sonic energy.
[0405] In one embodiment, one or more constituent of the at least
one adhesive agent includes a crosslinked constituent (such as
gelatin or albumin that is cross-linked with, for example,
glutaraldehyde), or a derivatized constituent (such as derivatized
collagen). In one embodiment, the at least one adhesive agent
includes one or more constituents that are configured to crosslink
with one or more substances in the at least one biological tissue.
The crosslinking bond can form upon administration of the at least
one adhesive agent to the at least one biological tissue, or upon
administration of at least one of a chemical agent (such as an
acid, base, enzyme, epoxide, diepoxide, 1,4-butanediol diglycidyl
ether, glutaraldehyde, polysaccharide, or other chemical agent),
air, moisture (such as from a biological fluid), electromagnetic
energy (including ultraviolet light), optical energy, thermal
energy, laser energy, ionizing radiation, non-ionizing radiation,
or sonic energy to the at least one adhesive agent.
[0406] In one embodiment, the at least one adhesive agent includes
one or more protein glue, including but not limited to protein,
peptide, or amino acid-based substances. In one embodiment, the at
least one adhesive agent includes one or more naturally-occurring
or synthetic component. In one embodiment, the at least one
adhesive agent includes one or more naturally-occurring or
synthetic polyphenolic protein from mussels, wherein the
polyphenolic protein is optionally cross-linked by a catechol
oxidase. In one embodiment, the at least one adhesive agent
includes mussel adhesive protein. In one embodiment, the mussel
adhesive protein includes lysine, hydroxylated amino acids, and
dopa. In certain instances, the mussel adhesive protein includes
dihydroxyphenylalanine. In one embodiment, the at least one
adhesive agent includes prolamine. In one embodiment, the at least
one adhesive agent includes one or more chemotactic agent, such as
transforming growth factor beta (TGF-.beta.).
[0407] In one embodiment, fibrin sealant or fibrin glue can be
formed as indicated in the table herein, or from two components:
one containing fibrinogen and calcium chloride solution and the
other containing thrombin solution and epsilon amino caproic acid
(EACA).
[0408] In one embodiment, the at least one adhesive agent includes
one or more hydrogel. See, for example, U.S. Pat. No. 6,103,528,
which is incorporated herein by reference. One non-limiting example
of a hydrogel included in a composition as described herein
includes polyethylene glycol, polylactic acid, polytrimethylene
carbonate, polycarophil, carbopol, polyox, chitosan,
polyvinylpyrrolidone, block polymers or block copolymers,
polymethylvinyl ether-maleic anhydride, or other constituents. In
certain embodiments, the hydrogel may include a constituent with a
polymerizable end cap, such as an acrylate ester. In one
embodiment, the at least one adhesive agent at least partially
generates a wound dressing, such as a sheet, bandage, film, or
other permeable, semi-permeable, or impermeable covering. In one
embodiment, the at least one wound dressing at least partially
includes natural, synthetic, or artificial skin or skin deposit.
(See, for example, Boateng et al., J. Pharm. Sciences. vol. 97, pp.
2892-2923 (2008)).
[0409] Some specific non-limiting examples of particular adhesive
agents that are included in at least one composition described
herein are listed in Table II herein. (Adapted from Smith, Ch. 7,
p. 574, Table 1; Ratner, et al, Biomaterials Science, Second
Edition, 2004; Elsevier Acad. Press., which is incorporated herein
by reference).
TABLE-US-00003 TABLE II Type of Possible setting or tissue
Components bonding reaction Cyanoacrylate Butyl or isobutyl
Addition polymerization cyanoacrylate Fibrin Fibrinogen (with or
without Clot formation sealant Factor XIII) Thrombin, CaCl.sub.2
Factor XIII Clot formation GRF glue Gelatin, resorcinol,
Condensation formaldehyde (glutaraldehyde or glyoxal can be used in
addition to or instead of formaldehyde) Hydrogel Block copolymers
of PEG, Photoinitiated addition polylactic acid and acrylate
polymerization esters Acrylic bone Methyl methacrylate and
Pertoxide-amine initiated cement polymethyl methacrylate addition
polymerization Dental Zinc oxide powder, Acid-base reaction, zinc
cements phosphoric acid complexation Zinc Zinc complexation
phosphate Zinc poly- Zinc oxide powder, aqueous Acid-base reaction,
zinc carboxylate polyacrylic acid complexation Glass Ca, Sr, Al
silicate glass Acid-base reaction, metal ionomer powder aqueous
poly- ion complexation (poly- acrylic-itatomic acid or alkenoate)
polyacrylic-maleic acid Resin-based Aromatic or urethane
Peroxide-amine or dimethacrylate monomers, photoinitiated silicate
or other glass polymerization and fillers aqueous polyacrylic
photoinitiated addition acid-itaconic acid-meth- polymerization
acrylate comonomers Resin- Hydroxyethyl methacrylate modified
aromatic or urethane glass diamethacrylates, Ca, Sr, Al ionomer
glass powder Dentin Etchant: phosphoric acid Photoinitiated
addition adhesive primer: carboxylate or polymerization phosphate
Monomers hydroxyethyl methacrylate/water/solvent Bonding agent:
urethane or aromatic dimethacrylate monomers
[0410] In one embodiment, the at least one adhesive agent is
configured to convert to at least one therapeutic agent upon
administration of the at least one adhesive agent. In one
embodiment, the at least one adhesive agent is configured to
undergo one or more of hydration, hydrolysis, hydrogenolysis,
condensation, dehydration, or polymerization upon administration of
the at least one adhesive agent. In one embodiment, the at least
one adhesive agent includes a methacrylate. In one embodiment, the
at least one adhesive agent includes at least one of
poly(N,N-dimethyl-N-(ethoxycarbonylmethyl)-N-[2'-(methacryloyloxy)ethyl]--
ammonium bromide) or poly(sulfobetaine methacrylate).
[0411] In one embodiment, the at least one adhesive agent is
configured to form one or more of a hydrogen bond, ionic bond,
covalent bond, or noncovalent bond with at least one substrate.
[0412] In certain instances, at least one adhesive agent is
provided to at least one substrate, including but not limited to at
least one biological tissue, in an inactive form. In certain
instances, the at least one adhesive agent is configured to
polymerize or activate during administration of the at least one
adhesive agent to at least one substrate, or shortly
thereafter.
[0413] In one embodiment, the at least one adhesive agent is
compatible with moist or wet tissues. In one embodiment, the at
least one adhesive agent distributes evenly over the tissue
surface. In one embodiment, the at least one adhesive agent quickly
forms a durable bond. In one embodiment, the bonding time of the at
least one adhesive agent is controllable. In one embodiment, the
bonding time of the at least one adhesive agent is controlled or
regulated. In one embodiment, the at least one adhesive degrades in
a relatively short period of time. In one embodiment, the at least
one adhesive agent is configured to be resorbed by the tissue to
which it is applied, or by the subject's body. In one embodiment,
the at least one adhesive agent maintains an appropriate viscosity
for the application, provides adequate working time prior to
bonding or setting, develops good adhesion, modulates hemostasis,
modulates wound healing, reduces fibrosis, or provides at least one
antimicrobial effect. In one embodiment, the at least one
composition including at least one adhesive provides a local depot
for at least one therapeutic agent.
[0414] In one embodiment, the at least one adhesive agent includes
an active surface (i.e. having a bioglass, calcium phosphate, or
biochemically active surface that can stimulate an in vivo
response). In one embodiment, the at least one adhesive agent
assists in delivering one or more therapeutic agents, including but
not limited to antibiotics, vaccines, growth factors (e.g., members
of the Fibroblast Growth Factor, members of the Bone Morphogenic
Protein family, members of the Transforming Growth Factor-beta
family, or others), transcription factors, anti-inflammatory
agents, pain relievers, hemostatic agents, chemotherapeutic agents
(e.g., 5-fluorouracil, paclitaxel, or others), chemokines,
cytokines, angiogenic or anti-angiogenic factors, enzymes, stem
cells, cellular organelles, or other therapeutic agents described
herein.
[0415] In one embodiment, the at least one adhesive agent is
delivered as a precursor molecule that is configured to activate by
an additional activation step or event. In one embodiment, two or
more components are configured to combine upon administration of
the at least one adhesive agent. In one embodiment, the combination
of the two or more components modifies at least one property of the
adhesive agent. In one embodiment, the at least one property
includes one or more of initiation of adhesive bond formation,
strength of adhesive bond, adhesive bonding time, bond flexibility,
bond biodegradability, bond bioresorbability, bond
biocompatibility, or durability of adhesive bond. In one
embodiment, the at least one property includes one or more of
polymerization of the adhesive agent, or crosslinking of the
adhesive agent. In one embodiment, two or more frozen particle
compositions, or frozen piercing implements are administered;
wherein at least one administration parameter is different for the
two or more frozen particle compositions, or frozen piercing
implements. In one embodiment, the at least one administration
parameter includes at least one of: constitution of the frozen
particle composition, or frozen piercing implement, formulation of
the frozen particle composition, or frozen piercing implement, size
of the frozen particle compositions, or frozen piercing implements,
shape of the frozen particle composition, or frozen piercing
implement, angle of administration of the frozen particle
composition, or frozen piercing implement, velocity of
administration of the frozen particle composition, or frozen
piercing implement, quantity of frozen particle compositions, or
frozen piercing implements administered, rate of administration of
more than one frozen particle composition, or frozen piercing
implement, spatial location for administration of the frozen
particle compositions, or frozen piercing implements, temporal
location for administration of the frozen particle compositions, or
frozen piercing implements, method of administration of the frozen
particle compositions, or frozen piercing implements, timing of
administration of the frozen particle compositions, or frozen
piercing implements, modulation of administration of the frozen
particle compositions, or frozen piercing implements, deposition of
the frozen particle compositions, or frozen piercing implements, or
rate of deposition of at least one agent included in the frozen
particle compositions, or frozen piercing implements.
[0416] In one embodiment, the at least one adhesive agent maintains
the approximation of tissue of at least one wound of a subject. In
one embodiment, the at least one adhesive agent forms a bond that
resists separation between at least two aspects of a substrate. In
one embodiment, the at least one adhesive agent is administered to
the at least one substrate, such as a biological tissue or
structure, prior to, during, or subsequent to a surgical procedure.
Specific, non-limiting examples of surgical procedures include
thoracic surgery, cardiovascular surgery, vascular surgery,
neurological surgery, plastic surgery or aesthetic surgery,
ophthalmic surgery, skin or connective tissue surgery, or abdominal
surgery.
[0417] In one embodiment, at least one frozen particle composition,
or frozen piercing implement includes an adhesive agent which
provides a means for the repair, closure, maintenance of
approximately the same tissue of a wound, treatment of a wound, or
joining at least one substrate to another or joining at least one
aspect of a substrate to another aspect of the same or different
substrate.
[0418] In one embodiment, and as described herein, compositions and
methods relate to the same or different frozen particle
compositions, or frozen piercing implements, and are administered
simultaneously, sequentially, randomly, or in another order. In
certain instances, the at least one composition is administered
that contains at least one adhesive agent as well as one or more
other agents, such as bonding agents, that include functional
groups or reactive side chains.
[0419] In one non-limiting example, polymerizable dimethacrylate
monomers mixed with composite formulations are administered to
calcified tissue, such as bone or tooth. In another non-limiting
example, acid etching or priming of the cell or tissue surface
(such as a calcified surface), is achieved by administration of
phosphoric acid or another acidic substance. In certain instances,
the acidic substance includes functional groups, such as
polycarboxylate or polyphosphate. Next, one or more agents can be
administered that react with the functional groups, such as
hydrophilic monomers (including but not limited to hydroxyethyl
methacrylate).
[0420] In one embodiment, the at least one adhesive agent forms one
or more of a hydrogen bond, ionic bond, covalent bond, or
non-covalent bond upon administration to at least one substrate. In
one embodiment the at least one adhesive agent includes at least
one crosslinking or derivatized agent. In one embodiment, the at
least one adhesive agent forms a crosslink bond with at least one
component of at least one substrate to which the adhesive agent is
administered. In one embodiment, the crosslink bond of the at least
one adhesive agent is modulated by one or more of a chemical agent,
change in pH, change in exposure to air, vacuum, change in moisture
content, change in pressure, or change in temperature. In one
embodiment, formation of a crosslink bond of the at least one
adhesive agent is modulated by exposure of the at least one
adhesive agent to one or more of electromagnetic energy, optical
energy, thermal energy, laser energy, ionizing radiation,
non-ionizing radiation, or sonic energy.
[0421] In one embodiment, adhesive agents can be selected for a
particular use as described herein, based on factors including, but
not limited to, viscosity, adhesive tenacity, kinetic rates of
monomer formation, polymerization (with or without covalent
cross-linking), ability to be cryoprecipitated, tensile strength,
ability to restore biomechanical tissue integrity, in vivo
effectiveness, or other factors. In certain instances, these or
other factors can be measured and selection of the one or more
particular adhesive agents can be based on those measurements. In
certain instances, these or other factors can be measured by
standard methods, including but not limited to, in vitro analysis,
in vivo experiments (e.g., animal studies), ex vivo experiments, in
planta experiments, or other methods.
[0422] In one embodiment, a method for providing at least one agent
to at least one substrate comprises administering at least one
frozen particle composition, or frozen piercing implement to at
least one substrate, wherein the at least one frozen particle
composition, or frozen piercing implement includes one or more
frozen particles as described herein, and at least one agent.
[0423] In one embodiment, a method for providing at least one
adhesive agent to at least one substrate comprises administering at
least one frozen particle composition, or frozen piercing implement
to at least one substrate, wherein the at least one frozen particle
composition, or frozen piercing implement includes one or more
frozen particles as described herein, and at least one adhesive
agent.
[0424] In one embodiment, a method of maintaining the approximation
of tissue of at least one wound of a subject comprises
administering at least one frozen particle composition, or frozen
piercing implement to at least one wound of a subject for a time
sufficient to maintain the approximation of tissue of the at least
one wound; wherein the at least one frozen particle composition, or
frozen piercing implement includes one or more frozen particle
compositions, or frozen piercing implements including at least one
agent (such as an adhesive agent, biological remodeling agent,
reinforcement agent, therapeutic agent, abrasive, or explosive
material) as described herein.
[0425] In one embodiment, the at least one frozen particle
composition, or frozen piercing implement includes a detection
state that varies with its adhesive state. In one embodiment, the
adhesive agent includes one or more eposy adhesive, acrylic
adhesive, urethane adhesive, polyurethane adhesive, silicone
adhesive, cationic adhesive, anerobic adhesive, urethane acrylate,
polyester acrylate, methacrylate, methyacrylate, or
cyanoacrylate.
[0426] In one embodiment, the at least one adhesive agent includes
at least one .alpha.-cyanoacrylate and a fluorescent compound
including at least one of a bis-benzoxazolyl compound, pyrylium
salt, quantum dot, or coumarin compound. In one embodiment, the at
least one adhesive agent includes an .alpha.-cyanoacrylate and
2,5-bis-(5-tert-butyl-2-benzoxasolyl)-thiophene. In one embodiment,
the at least one adhesive agent includes one or more of a base
component, initiator component, or activator component. In one
embodiment, the at least one adhesive agent further includes at
least one curing component. In one embodiment, the at least one
adhesive agent includes at least one photopolymerizable adhesive,
photocurable adhesive, thermal curable adhesive, free radical
curable adhesive, or aerobic curable adhesive. In one embodiment,
the at least one adhesive agent includes one or more adhesive agent
configured to polymerize upon exposure to infrared light,
ultraviolet light, x-ray, visible light, or other electromagnetic
radiation.
[0427] In one embodiment, the adhesive agent includes at least one
dye coinitiator. In one embodiment, the at least one dye
coinitiator includes at least one of a bis-benzoxazolyl compound,
pyrylium salt, QTX, safranine O, fluorescein, eosin yellow, eosin
Y, eosin B, ethyl eosin, eosin bluish, erythrosine B, erythrosine
yellowish blend, toluidine blue, 4',5'-dibromofluorescein, Rose
Bengal B, cyanine, pyronin GY, cresyl violet, brilliant green,
lissamine green BN, rhodamine B, methylene blue, crystal violet,
phosphine oxide, or coumarin compound.
Biological Remodeling Agents
[0428] In one embodiment, one or more frozen particle compositions,
or frozen piercing implements include at least one biological
remodeling agent. In one embodiment, the at least one biological
remodeling agent includes one or more extracellular matrix
components. In one embodiment, the at least one biological
remodeling agent is configured to provide at least one chemical or
biochemical function to the at least one biological tissue. In one
embodiment, the biological remodeling agent is configured to
modulate the growth of at least one biological tissue. In one
embodiment, the biological remodeling agent is configured to
promote growth of at least one biological tissue. In one
embodiment, the at least one biological remodeling agent is
configured to promote at least one of cell migration, cell
attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, angiogenesis, diffusion of materials,
nucleic acid expression, protein translation, protein modification,
protein secretion, carbohydrate production, carbohydrate secretion,
fat production, or fat secretion.
[0429] In one embodiment, the biological remodeling agent is
configured to inhibit growth of at least one biological tissue. In
one embodiment, the at least one biological remodeling agent is
configured to inhibit at least one of cell migration, cell
attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, angiogenesis, diffusion of materials,
nucleic acid expression, protein translation, protein modification,
protein secretion, carbohydrate production, carbohydrate secretion,
fat production, or fat secretion.
[0430] In one embodiment, the at least one biological remodeling
agent is configured to promote at least partial construction or at
least partial reconstruction of at least one biological tissue. In
one embodiment, the at least one biological remodeling agent
includes at least one cellular or tissue scaffolding component
(e.g., collagen, elastin, protein, carbohydrate, nucleic acid,
organic or inorganic agent, or other component). In one embodiment,
the at least one biological remodeling agent includes at least one
cell (e.g., endogenous cell, exogenous cell, transgenic cell,
progenitor cell, allogeneic cell, neonatal cell, embryonic cell,
stem cell, differentiated cell, blood cell, chondrocyte,
endothelial cell, hepatocyte, keratinocyte, myocyte, osteoblast,
osteoclast, osteocyte, mesenchymal cell, fibroblast, etc.), other
cells are described herein. (See, for example, Nolte et al., Cells
Tissues Organs vol. 187, pp. 165-176 (2008), which is incorporated
herein by reference.)
[0431] In one embodiment, the at least one biological remodeling
agent provides a scaffold or matrix for growth, regrowth,
restructuring, remodeling, or physically, chemically, or
biologically structuring one or more cells or biological tissues.
In one embodiment, the at least one biological remodeling agent is
configured to provide at least one mechanical structure to the at
least one biological tissue. In one embodiment, the at least one
biological remodeling agent provides a load-bearing structure to at
least one biological tissue.
[0432] In one embodiment, the at least one biological remodeling
agent is configured to provide oxygenation, nutrition, or other
nourishment to at least one biological tissue.
[0433] In one embodiment, the at least one biological remodeling
agent includes one or more self-organizing structures, including at
least one hydrogel, nanofiber, nanoparticle, or helical structure.
(See, for example, Pokroy et al, Science vol. 323, pp. 237-240
(2009); U.S. Patent Application Publication No. 20080070304, each
of which is incorporated herein by reference.) In one embodiment,
the at least one biological remodeling agent includes one or more
self-assembling nanofibers or nanoparticles.
[0434] In one embodiment, the at least one biological remodeling
agent at least partially generates a wound dressing, such as a
sheet, bandage, film, or other permeable, semi-permeable, or
impermeable covering. In one embodiment, the at least one wound
dressing at least partially includes natural, synthetic, or
artificial skin, skin substitute, or skin deposit. In one
embodiment, the at least one biological remodeling agent includes
at least one nanotube (such as a carbon nanotube, DNA nanotube, or
other nanotube).
[0435] In one embodiment, the at least one biological remodeling
agent includes at least one of a tumor antigen, microbial antigen,
viral antigen, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, chemical debridement agent, immunogen, antigen,
radioactive agent, apoptosis promoting factor, angiogenic factor,
anti-angiogenic factor, hormone, enzymatic factor, enzyme, papain,
collagenase, protease, peptidase, elastase, urea, vitamin, mineral,
nutraceutical, cytokine, chemokine, probiotic, coagulant,
anti-coagulant, phage, prodrug, prebiotic, blood sugar stabilizer,
smooth muscle cell activator, epinephrine, adrenaline, neurotoxin,
neuro-muscular toxin, Botulinum toxin type A, microbial cell or
component thereof, or virus or component thereof. In one
embodiment, the nutraceutical includes one or more of a flavonoid,
antioxidant, beta-carotene, anthocyanin, alpha-linolenic acid,
omega-3 fatty acids, yeast, bacteria, algae, other microorganisms,
plant products, or animal products.
[0436] In one embodiment, a frozen particle composition, or frozen
piercing implement, comprises: one or more frozen hydrogen oxide
particles that include at least one non-nucleic acid biological
remodeling agent.
[0437] In one embodiment, the at least one biological remodeling
agent is utilized in at least partially constructing or
reconstructing at least a portion of one or more biological .
tissues or organs. In on embodiment, the at least one biological
remodeling agent assists in the repair, enhancement, or replacement
of at least a portion of at least one biological tissue structure
or function. In one embodiment, the at least one biological
remodeling agent assists in restoring, maintaining, or improving at
least one tissue or organ function.
[0438] In one embodiment, at least one frozen particle composition,
or frozen piercing implement including at least one biological
remodeling agent or adhesive agent is utilized in at least
partially generating at least one biological tissue de novo. In one
embodiment, at least one frozen particle composition, or frozen
piercing implement including at least one biological remodeling
agent or adhesive agent is utilized in at least partially repairing
at least one damaged or diseased biological tissue. In one
embodiment, the at least one damaged or diseased biological tissue
is located in vivo. In one embodiment, the at least one damaged or
diseased biological tissue includes one or more wounds.
[0439] In one embodiment, a method includes at least partially
constructing or reconstructing at least one biological tissue or
organ by administering one or more frozen particle compositions, or
frozen piercing implements in such a manner that at least one agent
is deposited, wherein the one or more frozen particle compositions,
or frozen piercing implements include at least one biological
remodeling agent, at least one adhesive agent, at least one
therapeutic agent, at least one reinforcement agent, at least one
abrasive, at least one microneedle, or at least one explosive
material. In one embodiment, one or more frozen particle
compositions, or frozen piercing implements are deposited,
resulting in at least partially constructing or reconstructing at
least one biological tissue or organ.
[0440] In one embodiment, the at least one biological remodeling
agent is administered to at least one substrate, as described
herein. In one embodiment, the at least one biological remodeling
agent includes at least one nontoxic agent. In one embodiment, the
at least one biological remodeling agent includes a biocompatible,
bioresorbable, or biodegradable agent. In one embodiment, the at
least one substrate to which the one or more frozen particle
compositions, or frozen piercing implements are deposited or
administered is at least one of biocompatible, bioresorbable, or
biodegradable.
[0441] In one embodiment, at least one scaffold is utilized for
construction, reconstruction, or remodeling of at least one
biological tissue. In one embodiment, the at least one scaffold is
at least partially generated by deposition or administration of one
or more frozen particle compositions, or frozen piercing implements
including at least one biological remodeling agent. In one
embodiment, the at least one scaffold is at least one of
biocompatible, bioresorbable, or biodegradable.
[0442] In one embodiment, a template or molding is utilized for
deposition of one or more frozen particle compositions, or frozen
piercing implements including at least one biological remodeling
agent. In one embodiment, the frozen particle composition, or
frozen piercing implement includes one or more of a biological
remodeling agent, a therapeutic agent, abrasive, explosive
material, adhesive agent, or other agent. In one embodiment, the
template or molding is at least one of nontoxic, biocompatible,
bioresorbable, or biodegradable. In one embodiment, the one or more
biological remodeling agents, are deposited or administered
directly onto at least one substrate that is utilized in
constructing, reconstructing, or remodeling at least one biological
tissue.
[0443] In one embodiment, one or more frozen particle compositions,
or frozen piercing implements, including at least one biological
remodeling agent, are delivered to at least one scaffold, including
a three dimensional porous scaffold. In one embodiment, the
scaffold includes means for cell attachment, means for cell
proliferation, means for cell differentiation, means for cell
migration, means for cell contracting, means for cell expression,
means for cell matrix production, or means for cell spreading. In
one embodiment, the at least one scaffold includes seeding at least
one cell (e.g., a live cell) within at least one scaffold. In one
embodiment, seeding at least one cell within the at least one
scaffold occurs prior to, simultaneously with, or subsequent to, at
least partially generating, implanting, or transplanting the at
least one scaffold. In one embodiment, the at least one scaffold
includes injecting at least one biological remodeling agent and at
least one cell (e.g., a live cell) mixture to the at least one
substrate for at least partially constructing, reconstructing, or
remodeling at least one biological tissue. In one embodiment, the
scaffold is at least partially generated, implanted, or
transplanted and is eventually seeded with a subject's own cells,
either naturally or artificially.
[0444] In one embodiment, the at least one biological remodeling
agent includes one or more of calcium phosphate, albumin, cytokine,
pegylated cytokine, bone, cartilage, globulin, fibrin, thrombin,
glutaraldehyde-crosslinked pericardium, hide powder, hyaluronic
acid, hydroxyapatite, keratin, ligament, nitinol, nucleic acid
polymers, polyethylene, polylethylene glycol, polyethylene glycol
diacrylate, polyethylene terephthalate fiber, polyglycol,
polylactate, polytetrafluoroethylene, polylactic acid, polyglycolic
acid, polycaprolactone, PURAMATRIX.TM. self-assembly peptide
hydrogel fibers, linear aliphatic polyester, tendon, fibrinogen,
hyaluronate, chitin, chitosan, methylcellulose, alginate,
hyaluronic acid, agarose, cellulose, polyaldehyde gluronate, Factor
XIII, Factor XII, silk, nylon, collagen, elastin, silicone,
polyurethane, ceramic powder, pectin, wax, glycosaminoglycan,
poly(.alpha.-hydroxyacid), selectin, glutaraldehyde, hydrophobic
non-glycosylated protein, hydrogel, peptide hydrogel, or
gelatin.
[0445] In one embodiment, the at least one biological remodeling
agent includes one or more of Type I collagen, Type II collagen,
Type III collagen, Type VII collagen, or Type X collagen. In one
embodiment, the at least one biological remodeling agent includes
one or more of elastin fibers or soluble elastin.
[0446] In one embodiment, the biological remodeling agent includes
at least one member of the Transforming Growth Factor .beta.
superfamily, including but not limited to bone
morphogenetic/osteogenic proteins (BMPs/OPs), growth
differentiation factors, activin A and B, inhibin A and B,
Anti-mullerian hormone, Nodal, TGF-.beta. type receptors such as
Activin Type I receptors, Activin Type II receptors,
transducers/SMAD molecules, ligand inhibitors (e.g., Cerberus,
chordin, Dan, Decorin, Follistatin, Gremlin, Lefty, LTBP1, Noggin,
THBS1), co-receptors (e.g., BAMBI-Cripto), SARA, or other
molecules. (See, for example, Aarabi et al., PLOS Med., vol. 4,
Issue 9, pp. 1464-1470 (2007). In one embodiment, the at least one
biological remodeling agent includes one or more of epidermal
growth factor (EGF), platelet derived growth factor (PDGF),
fibroblast growth factor (FGF), insulin-like growth factor (IGF-1),
human growth hormone, granulocyte-colony stimulating factor
(G-CSF), or granulocyte-macrophage colony-stimulating factor
(GM-CSF). In one embodiment, one or more biological remodeling
agents include at least one nucleic acid. In one embodiment, one or
more biological remodeling agents include at least one RNA or DNA
molecule. In one embodiment, the one or more biological remodeling
agents include at least one of a protein, carbohydrate, or fat.
[0447] Some other non-limiting examples of biological remodeling
agents, as well as the general but non-limiting solidification
mechanism of each, are set forth in Table III below. Abbreviations
include: OPF: oligo(poly(ethylene glycol) fumarate); P(CL/TMC):
poly(-caprolactone-co-trimethylene carbonate); PDLLA:
poly(D,L-lactide); PEG: poly(ethylene glycol); PEO: poly(ethylene
oxide); PEO-PPO-PEO: polyethylene oxide-polypropylene
oxide-polyethylene oxide; PhosPEG-dMA: poly(ethylene glycol)
di[ethylphosphatidyl(ethylene glycol)methacrylate]; PLA(Glc-Ser):
Poly(L-lactic acid-co-glycolic acid-co-L-serine); PLA-PEG:
poly(lactic acid)-poly(ethylene glycol; PLAL-ASP: Poly(lactic
acid-co-lysine)-poly(aspartic acid); PLGA:
Poly(DL-lactic-co-glycolic acid); PLLA: poly(L-lactic acid);
PLLA-PEG: poly(L-lactide-ethylene glycol); PNIPAAm:
poly(N-isopropylacrylamide); P(NIPAAm-AAc):
Poly(N-isopropylacrylamide-acrylic acid); PPF: poly(propylene
fumarate); P(PF-co-EG): poly(propylene furmarate-co-ethylene
glycol; PVA: poly(vinyl alcohol). (See, for example, Hou et al., M.
Mater. Chem., vol. 14, pp. 1915-1923 (2004), which is incorporated
herein by reference.)
TABLE-US-00004 TABLE III Biological Remodeling Agent Solidification
mechanism Calcium phosphate Ceramics setting Chitosan Thermal
gelation Methylcellulose Thermal gelation Alginate Photo
cross-linking or ionic gelation Hyaluronic acid Photo cross-linking
Agarose Thermal gelation Fibrin Thermal gelation Gelatin Thermal
gelation Poly(aldehyde gluronate) Chemical cross-linking PEG or PEO
Photo cross-linking PEO-PPO-PEO Thermal gelation PEO-PLLA-PEO Photo
cross-linking PLA-g-PVA Photo cross-linking PEO-PLLA Thermal
gelation PLGA-PEG Thermal gelation PEG-co-Poly(.alpha.-hydroxy
acid) Photo cross-linking PVA, PLAL-ASP, P(CL/TMC), PLA(Glc- Photo
cross-linking Ser), or Polyanhydrides PPF, OPF, or P(PF-co-EG)
Photo cross-linking or radical polymerization PhosPEG-dMA Photo
polymerization PNIPAAm-PEG, PNIPAAm-gelatin, Thermal gelation
P(NIPAAm-AAc) PEG based hydrogels Enzymatic cross-linking or
Michael-type addition reaction PLA-PEG-biotin Self-assembly
[0448] In one embodiment, at least one frozen particle composition,
or frozen piercing implement is administered to at least one
substrate by pushing, pulling, drilling, utilizing a screw-type
action, propelling, ejecting, or accelerating a plurality of frozen
particle compositions, or frozen piercing implements toward the at
least one substrate. In one embodiment, propelling, ejecting, or
accelerating the plurality of frozen particle compositions, or
frozen piercing implements toward the at least one substrate
includes at a predetermined angle, a predetermined velocity, a
predetermined rate of administration, a predetermined spatial
pattern, a predetermined location, a predetermined time sequence,
or a predetermined depth. In one embodiment, two or more of the
plurality of frozen particle compositions, or frozen piercing
implements include two or more biological remodeling agents
configured to physically or chemically bind upon administration. In
one embodiment, administering the one or more frozen particle
compositions, or frozen piercing implements to at least one
substrate includes contacting the at least one substrate with the
one or more frozen particle compositions, or frozen piercing
implements. In one embodiment, administering the one or more frozen
particle compositions, or frozen piercing implements to at least
one substrate includes contacting the at least one substrate with
the at least one biological remodeling agent.
Substrates
[0449] In one embodiment, the one or more frozen particle
compositions, frozen piercing implements, or frozen piercing
implement devices are administered to at least one substrate.
Specific non-limiting examples of various different substrates are
provided throughtout the application.
[0450] In one embodiment, the at least one substrate includes at
least one nontoxic, biodegradable, bioresorbable, or biocompatible
substrate. In one embodiment, the at least one substrate includes
one or more of a cell, tissue, organ, structure, device, or food
product. In one embodiment, the substrate includes at least a
portion of which is naturally, artificially, or synthetically
derived. In one embodiment, the substrate includes at least a
portion of which is genetically altered. In one embodiment, at
least one frozen particle composition, or frozen piercing implement
is administered to at least one cell or cell component for gene
delivery.
[0451] In one embodiment, the structure or device may include a
prosthesis, cell matrix or scaffold, tissue matrix or scaffold,
supplement, implement, bandage, tourniquet, wound dressing, splint,
stent, patch, gauze, covering, shunt, needle, scalpel, matrix,
sponge, mesh, woven fabric, knitted fabric, film, instrument, or
other tool or item. (See, for example, U.S. Patent Application
Publication No. 20070021816, which is incorporated herein by
reference.) In one embodiment, the device includes at least one
mechanical or electrical device. In one embodiment, the device
includes, but is not limited to, at least one mechanical or
electrical device. Examples of particular devices are described
herein.
[0452] In one embodiment, the substrate is located in at least one
of in situ, in vitro, in vivo, in utero, in planta, in silico, or
ex vivo. In one embodiment, the at least one substrate is
transplanted or implanted into at least one subject. In one
embodiment, the at least one substrate is ingested by at least one
subject. In one embodiment, the at least one substrate includes at
least one biological cell or tissue. In one embodiment, the at
least one biological cell or tissue is from at least one donor or
recipient. In one embodiment, the at least one donor includes at
least one cadaver. In one embodiment, the at least one substrate
includes at least one implantable or transplantable substrate. In
one embodiment, the at least one substrate is transplanted or
implanted into at least one subject. In one embodiment, the at
least one substrate includes at least one biological tissue from at
least one donor or recipient.
[0453] In one embodiment, the temperature of the substrate is
adjusted for administration of one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
temperature of the substrate is increased or decreased in order to
adjust the rate of melting, sublimation, evaporation,
transformation, activation, etc. of the one or more frozen particle
compositions, or frozen piercing implements or a component
thereof.
[0454] In one embodiment, the pressure exerted on a substrate is
adjusted for administration of one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
pressure exerted on a substrate is increased or decreased in order
to adjust the rate of melting, sublimation, evaporation,
transformation, activation, etc. of the one or more frozen particle
compositions, or frozen piercing implements or a component thereof.
In one embodiment, the at least one substrate includes at least one
polymer or hydrogel.
[0455] In one embodiment, the at least one agent is delivered to a
single biological cell or tissue. In one embodiment, the at least
one substrate is ingested by at least one subject.
[0456] In one embodiment, the at least one substrate includes at
least one implantable or transplantable substrate. In one
embodiment, the at least one substrate is transplanted or implanted
into at least one subject. In one embodiment, the substrate
includes at least one biological tissue from at least one donor or
recipient. In one embodiment, the at least one substrate includes
at least a portion of at least one subject. In certain embodiments,
administering at least one frozen particle composition or frozen
piercing implement includes self-administering the at least one
frozen piercing implement by the at least one subject.
[0457] In one embodiment, the at least one biological tissue
includes one or more of a plant part, or whole plant. In one
embodiment, the at least one biological tissue includes one or more
of a stalk, stem, leaf, root, or tendril. In one embodiment, the at
least one biological tissue includes at least one of meristem
tissue, plant embryo tissue, cotyledon tissue, shoot apex tissue,
scutellum tissue, epicotyl tissue, hypocotyl tissue, stamen tissue,
receptacle tissue, anther tissue, stigma tissue, ovary tissue,
carpel tissue, endosperm tissue, or seed germ tissue. In one
embodiment, the at least one biological tissue includes transgenic
tissue. In one embodiment, the transgenic tissue includes meristem
tissue cells for later generations. Non-limiting examples of plants
that are included are cereal crops, fruits, nuts, vegetables, woody
species, ornamental flower, cash crops (e.g., tobacco), and other
plants.
[0458] In one embodiment, one or more frozen particle compositions,
or frozen piercing implements are delivered to a substrate
including at least one food or beverage product, or other product
for consumption. In one embodiment, the at least one food product
includes one or more of an animal, plant, fungal, or other
biological food product. In one embodiment, the at least one food
product includes at least one non-biological based food product. In
one embodiment, the at least one food product includes, but not
limited to at least one of a grain product; vegetable, fruit, leaf,
stem, or other plant product; meat, milk, eggs, or other animal
product; including processed products thereof. In one embodiment,
one or more frozen particle compositions, or frozen piercing
implements are delivered to at least one of a juice, cut food
product, canned food product, pulped food product, frozen food
product, homogenized food product, sterilized food product,
dehydrated food product, or otherwise processed food product. In
one embodiment, one or more frozen particle compositions, or frozen
piercing implements include at least one component of a food
product.
[0459] In one embodiment, one or more frozen particle compositions,
or frozen piercing implements are delivered to at least one product
for consumption. In one embodiment, the product for consumption
includes, but is not limited to at least one of a hygienic product
(e.g., toothpaste, deodorant, perfume, shampoo, soap, etc.), a
cosmetic product (e.g., lotion, lipstick, nail polish, or other
facial cosmetics, etc.).
[0460] In one embodiment, one or more frozen particle compositions,
or frozen piercing implements are delivered to at least one outdoor
or indoor area (e.g., road surface, carpet, ice rink, garden,
jungle, etc.).
[0461] In one embodiment, the substrate includes, but is not
limited to, biological tissue as described herein. For example,
biological tissue includes soft tissues (such as connective tissue,
or other soft tissue), or hard tissues (including calcified
tissues, such as bone or teeth). In one embodiment, a cell
includes, but is not limited to, at least one of an autologous
cell, allogenic, xenogenic, stem cell, or syngenic cell. The one or
more cells may include endogenous or exogenous cells relative to a
particular subject. In one embodiment, the at least one substrate
includes one or more stem cells (e.g., hematopoietic stem cells,
adipocyte stem cells, neuronal stem cells, embryonic stem cells,
hepatic stem cells, dermal stem cells, pancreatic stem cells, stem
cells related to bone, stem cells related to muscle, or others). In
one embodiment, the substrate includes at least one wound, or cell
mass. Other examples of cells and biological tissues are described
herein at other sections.
[0462] In one embodiment, the at least one biological tissue
includes but is not limited to, one or more of cartilage, skin,
scalp, hair, nail, nail bed, teeth, eye, ear, ovary, oviduct,
tongue, tonsil, adenoid, liver, bone, pancreas, stomach, appendix,
duct, valve, smooth muscle, blood vessel, bone marrow, blood,
lymph, heart, lung, brain, breast, kidney, bladder, urethra,
ureter, gall bladder, uterus, prostate, testes, vas deferens,
fallopian tubes, large intestine, small intestine, esophagus, oral
cavity, nasal cavity, otic cavity, connective tissue, muscle
tissue, or adipose tissue. In one embodiment, the at least one
tissue includes one or more of a tendon, vein (e.g., femoral or
saphenous vein), artery, or capillary. In one embodiment, the at
least one biological tissue includes embryonic or fetal tissue. In
one embodiment, the at least one biological tissue includes a
mucosal surface. In one embodiment, the at least one biological
tissue includes a plant, animal, fungal or other food product
(e.g., biological food product). In one embodiment, the at least
one biological tissue includes meat.
[0463] In one embodiment, the treatment of at least one biological
tissue includes one or more of ossicular chain reconstruction in
otlogic surgery, nerve anastomosis (e.g. peripheral nerve
anastomosis); cerebralspinal fluid sealing in neurological repair,
vascular repair or anastomosis, ocular repair, gastrological
repair, urological repair, skin closure, bronchial repair (e.g.
bronchial stump leakage), alveolar repair, or dental fillings. In
one embodiment, the at least one biological tissue includes fetal
tissues or organs (e.g. in utero) and can include any of the
tissues or organs described herein.
[0464] In one embodiment, the at least one biological tissue is
located in at least one tissue or organ related to transplantation.
In one embodiment, transplantation includes extraction or
implantation of the at least one tissue or organ. In one
embodiment, the at least one tissue or organ related to
transplantation is extracted from at least one first biological
source or subject and implanted into at least one second biological
source or subject. In one embodiment, the at least one tissue or
organ related to transplantation is cultured prior to implantation
in a subject. In one embodiment, the tissue or organ related to
transplantation is an artificial or synthetically derived tissue or
organ (e.g. a bladder, heart, kidney, liver, pancreas, skin, eye,
lung, nerve, blood vessel, and others). In one embodiment, the
tissue or organ related to transplantation involves at least two
sources (i.e. multiple species, partially artificial or synthetic,
multiple biological cells or tissues including stem cells). In one
embodiment, the at least one tissue or organ related to
transplantation includes at least one donor or recipient tissue or
organ. In one embodiment, the at least one tissue or organ is at
least partly autologous.
[0465] In one embodiment, one or more blood vessels, including at
least one of a vein, artery, or capillary is at least partially
made by utilizing one or more frozen particle compositions, or
frozen piercing implements. In one embodiment, the one or more
blood vessels include at least one vascular graft at least
partially made by utilizing one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
at least one vascular graft includes at least one autologous
component. See, for example, McAllister et al., Abstract, Lancet,
vol. 373, No. 9673, pp. 1440-1446 (2009), which is incorporated
herein by reference.
[0466] In one embodiment, the at least one substrate includes at
least one cell mass. In one embodiment, the at least one cell mass
includes at least one of a scar, pore, pit, eschar, granuloma,
keloid, artheromatous plaque, abscess, pustule, scaling (e.g.,
psoriasis or eczema), infected tissue, hair follicle, necrotic
tissue, stratum corneum, wrinkle, wound, tumor, skin structure,
nevus, cyst, lesion, callus, neoplastic tissue, gangrenous tissue,
or cellular deposit. In one embodiment, the at least one cell mass
includes at least one benign or malignant tumor. In one embodiment,
the at least one benign or malignant tumor relates to one or more
of a melanoma, lymphoma, leukemia, sarcoma, blastoma, or
carcinoma.
[0467] In one embodiment, the at least one cell mass is related to
at least one blood clot, embolus, microorganism accumulation, blood
vessel obstruction, duct obstruction, bowel obstruction, infection,
gangrene, connective tissue destruction, tissue or organ damage,
injury, white blood cell accumulation, or cancer.
[0468] In one embodiment, the at least one substrate includes one
or more wounds. In one embodiment, the one or more wounds are
located in at least one biological tissue or organ. In one
embodiment, the one or more wounds are located in one or more of
skin tissue, muscle tissue, eye tissue, nervous tissue, peritoneal
tissue, an organ, connective tissue, neoplastic tissue, or bone
tissue.
[0469] In one embodiment, the one or more wounds are located in at
least one subject. The one or more wounds include but are not
limited to at least one of an incision (including surgical incision
such as for facial or other aesthetic construction or
reconstruction, or other cranio-facial surgeries, laproscopic
procedures, birthing assistance, or other surgical procedures),
fracture, irritation, episiotomy, laceration, endovascular
occlusion (e.g., aneurism), blood vessel anastomosis, nerve repair,
abrasion, cerebral spinal fluid leak, puncture wound, penetration
wound, gunshot wound, iatrogenic wound, severing, infection, ulcer,
pressure sore, lesion, chemical burn (including but not limited to
exposure to an irritant, plant, or synthetic chemical), dental
caries, first-degree burn, second-degree burn, third-degree burn,
fourth-degree burn, fifth-degree burn, or sixth-degree burn. In
certain instances, the wound can be a result of a bite, such as a
bite from an animal, insect, or arachnid.
[0470] In one embodiment, the at least one subject includes one or
more of a vertebrate or invertebrate animal. In one embodiment, the
at least one subject includes a fungus, or plant (including crop
plants, as described herein). In one embodiment, the at least one
subject includes insect cells, insects, bacteria, algae, plankton,
or protozoa. In one embodiment, the at least one subject includes
one or more of a reptile, mammal, amphibian, bird, or fish. In one
embodiment, the at least one subject includes at least one human.
In one embodiment, the at least one subject includes at least one
of livestock, pet, zoo animal, undomesticated herd animal, wild
animal, or product animal.
[0471] In one embodiment, the at least one subject includes at
least one of a sheep, goat, frog, dog, cat, rat, mouse, vermin,
monkey, duck, horse, cow, pig, chicken, shellfish, fish, turkey,
llama, alpaca, bison, buffalo, ape, primate, ferret, wolf, fox,
coyote, deer, rabbit, guinea pig, yak, chinchilla, mink, reindeer,
elk, camel, fox, elk, deer, raccoon, donkey, or mule.
Detection Materials
[0472] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements include at least one of
a polymer, biopolymer, nanoparticle, sensor, micro-syringe,
actuator, circuit, or other detection material. Such detection
materials may allow for visualization of the one or more frozen
particle compositions, or frozen piercing implements, the
administration process, or provide other benefits (including but
not limited to reinforcement, adhesive, biological remodeling,
abrasive, explosive, or therapeutic benefits). In one embodiment,
the nanoparticle includes one or more of a nanorod, nanobone,
nanocapsule, or other particle. In one embodiment, the nanoparticle
releases its payload when exposed to an energy source, including
heat or light. In one embodiment, the nanoparticles have a
time-release payload of, for example, one or more therapeutic
agents, adhesive agents, biological remodeling agents,
reinforcement agents, abrasives, explosive materials, or other
agents.
[0473] In certain instances, the detection material can be located
on or in the one or more frozen particle compositions, or frozen
piercing implements, or it can be intermixed with the one or more
frozen particle compositions, or frozen piercing implements. In
certain instances, the detection material provides a "tracer" agent
that allows for visualization of one or more locations of
administration of the at least one frozen particle composition, or
frozen piercing implement. For example, in one embodiment, the
detection material includes a particle with altered isotopes (e.g.,
for altering the mass of particles as a tracer). In one embodiment,
only certain frozen particle compositions, or frozen piercing
implements of a plurality of frozen particle compositions, or
frozen piercing implements include one or more detection materials.
In one embodiment, one or more detection materials are included in
one or more frozen particle compositions, or frozen piercing
implements in a predictable or predictive manner, for example,
about every 2.sup.nd, about every 3.sup.rd, about every 4.sup.th,
about every 5.sup.th, about every 6.sup.th, about every 7.sup.th,
about every 8.sup.th, about every 9.sup.th, about every 10.sup.th,
about every 20.sup.th, about every 50.sup.th, about every
100.sup.th, about every 1000.sup.th, about every 2000.sup.th, or
about every 5000.sup.th, etc. frozen particle composition, or
frozen piercing implement includes one or more detection
materials.
[0474] In certain instances the detection material is located on
the at least one frozen particle composition, or frozen piercing
implement or the at least one frozen particle. In other instances,
the detection material is separate from the at least one frozen
particle composition, or frozen piercing implement. In certain
instances, the detection material forms a mixture with the frozen
particle composition, or frozen piercing implement. In certain
instances, the detection material is separate from the one or more
frozen particle compositions, or frozen piercing implements and is
administered at approximately the same time, in approximately the
same place, or in approximately the same manner as the one or more
frozen particle compositions, or frozen piercing implements. In one
embodiment, the detection material is located in at least one
cavity or compartment of the one or more frozen particle
compositions, or frozen piercing implements.
[0475] In one embodiment, detection material includes a detection
label including but not limited to, a colorimetric label, a
radioactive label, a light-emitting label (such as a luminescent
compound, a fluorescent compound, a phosphorescent compound, or a
quantum dot), a nucleic acid label, a protein label, an antibody
label, a ligand label, a receptor label, a magnetic label, or other
detection label. In one embodiment, the at least one detection
material includes but is not limited to, at least one electronic
identification device. In one embodiment, the at least one
electronic identification device includes at least one radio
frequency identification device.
[0476] In one embodiment, the at least one detection material
includes but is not limited to, at least one radioactive element.
In one embodiment, the radioactive element includes but is not
limited to, .sup.32P, .sup.35S, .sup.13C, .sup.131I, .sup.191Ir,
.sup.192Ir, .sup.193Ir, .sup.201Tl, or .sup.3H. In one embodiment,
the at least one detection material includes at least one
radioactive, luminescent, colorimetric or odorous substance. In one
embodiment, the at least one colorimetric substance includes one or
more of an inorganic, organic, biological, natural, artificial, or
synthetic substance. The colorimetric substance may include, but
not be limited to a dye or a pigment. The colorimetric substance
may include a chromogenic substrate.
[0477] In one embodiment, the at least one detection material
includes at least one light-emitting substance, such as a
luminescent substance, a fluorescent substance, phosphorescent
substance, or quantum dot. In one embodiment, the at least one
detection material is nontoxic, biocompatible, bioresorbable, or
biodegradable.
[0478] Some examples of colorimetric substances include, but are
not limited to, colored agents that have an affinity for a cell or
tissue, such as acid dyes (e.g., water-soluble anionic dyes), basic
dyes (e.g., water-soluble cationic dyes), direct or substantive
dyes (e.g., stains for nucleic acids, proteins, lipids,
carbohydrates, cell populations, tissues, or organelles), mordant
dyes, vat dyes, reactive dyes, disperse dyes, azo dyes, sulfur
dyes, food dyes, solvent dyes, carbene dyes, or others. Some
examples of chromophores that can be utilized include, but are not
limited to, dyes that are based on or derivatives of acridine,
anthraquinone, arymethane (e.g., diphenyl methane, triphenyl
methane), --N.dbd.N azo structure, phthalocyanine, diazonium salts,
--NO.sub.2 nitro functional group, --N.dbd.O nitroso functional
group, phthalocyanine, quinine, azin, eurhodin, safranin, indamin,
indophenol, oxazin, oxazone, thiazin, thiazole, xanthene, fluorine,
pyronin, fluorine, rhodamine, or others. In one embodiment, the
colorimetric substance includes trypan blue.
[0479] In one embodiment, the detection material includes at least
one light-emitting substance, including but not limited to
luminescent substances (e.g. bioluminescent substances,
chemiluminescent substances, luciferin, isoluminol, luminescent
minerals, etc.). In one embodiment, the detection material includes
one or more one or more fluorescent tags, including but not limited
to fluorescein, phycobilin, phycoerythrin, phycourobilin,
chlorophyll, phycocyanin, allophycocyanin, green fluorescent
protein, or others. In one embodiment, the at least one detection
material includes but is not limited to, at least one of a
diamagnetic particle, ferromagnetic particle, paramagnetic
particle, super paramagnetic contrast agent, particle with altered
isotope, or other magnetic particle.
[0480] Some non-limiting examples of particular diamagnetic
substances include wood, water, organic compounds (such as
petroleum), metals (including copper, mercury, gold, bismuth), or
benzoic acid.
Methods, Devices, Systems for Administering a Frozen Particle
Composition or Frozen Piercing Implement
[0481] As described herein, a device or machine (including a
computer) may be utilized in various aspects relating to
compositions, methods, or systems relating to one or more frozen
particle compositions, or frozen piercing implements (or the
devices thereof). Non-limiting examples of such aspects may include
predicting or calculating various properties or characteristics
relating to the one or more frozen particle compositions, or frozen
piercing implements, any substrate, any subject, any administration
device, or any administration protocol. Any method disclosed herein
is implicitly intended to also include "means for" carrying out the
method. One or more methods disclosed include computer-implemented
methods.
[0482] In one embodiment, a method or means for making one or more
frozen particle compositions, or frozen piercing implements
optionally includes at least one agent. In one embodiment, a method
or means for administering or delivering one or more frozen
particle compositions, or frozen piercing implements is disclosed.
In one embodiment, a method or means for administering at least one
frozen particle composition, or frozen piercing implement includes
administering at least one agent to a substrate.
[0483] In one embodiment, the at least one agent may provide
promoting wound healing; promoting healing of skin, cartilage, or
bone; filling of skin wrinkles or flaws; filling of connective
tissue; treating vesico-ureteral reflux; treating urinary
incontinence; fixing prostheses or materials to at least one
biological tissue; or producing at least one film, gel, or membrane
for use in vitro or in vivo to assist in a biological function.
[0484] In one embodiment, a method or means for of providing at
least one agent, such as a biological remodeling agent, to at least
one substrate comprises administering one or more frozen particle
compositions to at least one substrate, wherein the one or more
frozen particle compositions, or frozen piercing implements include
at least one biological remodeling agent as described herein. In
one embodiment, the one or more frozen particle compositions, or
frozen piercing implements have one or more phases including at
least one of amorphous solid water, low density amorphous ice, high
density amorphous ice, very high density amorphous ice, clathrate
ice, hyperquenched glassy water, ice Ic, ice II, ice III, ice IV,
ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, ice XII,
ice XIII, ice XIV, or ice XV. In one embodiment, the one or more
frozen particle compositions, or frozen piercing implements
including one or more frozen particles and at least one agent have
one or more phases including at least one of amorphous solid water,
low density amorphous ice, high density amorphous ice, very high
density amorphous ice, clathrate ice, hyperquenched glassy water,
ice Ic, ice II, ice III, ice IV, ice V, ice VI, ice VII, ice VIII,
ice IX, ice X, ice XI, ice XII, ice XIII, ice XIV, or ice XV.
[0485] In one embodiment, a method or means for at least partially
constructing or at least partially reconstructing at least one
biological tissue or organ comprises administering one or more
frozen particle compositions, or frozen piercing implements that
include at least one agent (such as at least one of a biological
remodeling agent, adhesive agent, therapeutic agent, reinforcement
agent, abrasive, or explosive material) in such a manner that the
at least one agent is deposited. In one embodiment, the at least
one agent includes at least one biological remodeling agent.
[0486] In one embodiment, the method or means for includes abrading
or ablating one or more surfaces of the at least one substrate
prior to, during, or subsequent to the administering of the one or
more frozen particle compositions, or frozen piercing implements.
In one embodiment, the method or means for administering one or
more frozen particle compositions, or frozen piercing implements is
provided in such a manner as to induce at least one cellular event.
In one embodiment, the at least one cellular event includes one or
more of: cell migration, cell attachment, cell retention, cell
differentiation, cell proliferation, apoptosis, diffusion of
materials, angiogenesis, nucleic acid expression, protein
translation, protein modification, carbohydrate production,
carbohydrate secretion, protein secretion, fat production or fat
secretion. In one embodiment, the method further includes
administering at least one component including an optical,
photonic, or electronic article. In one embodiment, the at least
one article is configured to communicate with at least one computer
system. In one embodiment, the at least one article is configured
to monitor at least one characteristic of the at least one
biological tissue.
[0487] As described herein, in one embodiment, computer-aided
tissue engineering (CATE) is utilized in the design (including
tissue scaffold design), image processing, predicting, modeling,
simulation, manufacturing, administration or delivery of at least
one frozen particle composition, or frozen piercing implement,
informatics (including computer-aided tissue classification and
application for tissue identification and characterization at
different tissue hierarchical levels), or other aspects of tissue
reconstruction with one or more frozen particle compositions, or
frozen piercing implements described. In one embodiment,
computer-aided tissue engineering compares information regarding at
least one of design, image processing, predicting, modeling,
simulation, manufacturing, administration or delivery of at least
one frozen particle composition, or frozen piercing implement, or
informatics for at least one biological tissue with at least one
dataset or database. In one embodiment, a dataset or database is
generated from information regarding at least one of design, image
processing, predicting, modeling, simulation, manufacturing,
administration or delivery of at least one frozen particle
composition, or frozen piercing implement, informatics, or other
aspect of tissue reconstruction with one or more frozen particle
compositions, or frozen piercing implements described.
[0488] In one embodiment, ink jet printing is utilized for
stereo-model fabrication, or for direct biological tissue
construction, reconstruction, or remodeling through deposition or
administration of one or more frozen particle compositions. (See,
for example, Mironov, et al, Trends in Biotech. Vol. 21, No. 4; pp.
157-161 (2003), which is incorporated herein by reference.) In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements include one or more agents that fuse upon
administration or deposition. (See, for example, Jakab, et al,
Tissue Eng. Part A, Vol. 14, No. 3 pp. 413-421 (2008), which is
incorporated herein by reference.)
[0489] In one embodiment, at least one of rapid prototyping
(including but not limited to stereolithography), fused deposition
modeling, three-dimensional printing, selective deposition
modeling, solid free-form fabrication (SFF), selective laser
sintering, laminated object manufacturing, gas foaming, solvent
casting and particulate leaching, emulsification, freeze-drying,
phase separation, shape deposition manufacturing, or other method
is utilized with administration of one or more frozen particle
compositions, or frozen piercing implements for tissue
reconstruction. (See, for example, U.S. Patent Application
Publication No. 20040075196; Barry, et al., Phil. Trans. R. Soc. A
vol. 364, pp. 249-261 (2006); and U.S. Patent Application
Publication No. 20080145639, each of which is incorporated herein
by reference.) In one embodiment, a model is used for designing or
developing the architecture of the at least one biological tissue
prior to administering or depositing the one or more frozen
particle compositions, or frozen piercing implements for at least
partially constructing, at least partially reconstructing, or at
least partially remodeling at least one biological tissue. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements are administered or deposited directly onto at
least one substrate for at least partially constructing, at least
partially reconstructing, or at least partially remodeling at least
one biological tissue. In one embodiment, the at least partial
reconstruction, at least partial construction, or at least partial
remodeling of at least one biological tissue includes depositing at
least one agent of at least one frozen particle composition, or
frozen piercing implement. In one embodiment, the at least partial
reconstruction, at least partial construction, or at least partial
remodeling of at least one biological tissue includes at least
partially abrading or ablating at least one surface of at least one
substrate (e.g., biological tissue) with at least one frozen
particle composition, or frozen piercing implement.
[0490] In one embodiment, sample cells are grown ex vivo,
introduced with scaffold in the appropriate environment for cell or
tissue growth utilizing one or more frozen particle compositions,
or frozen piercing implements, and the cells implanted or
transplanted into at least one subject. (See, for example, Sun et
al., Biotechnol. Appl. Biochem. vol. 39, pp. 29-47 (2004), which is
incorporated herein by reference.)
[0491] Computer-aided tissue modeling utilized in conjunction with
certain embodiments for administration of one or more frozen
particle compositions, or frozen piercing implements includes
imaging data acquisition. For example, a medical imaging modality
must be capable of one or more of producing three-dimensional views
of anatomy, differentiating heterogenous tissue types and
displaying the vascular structure, as well as generating
computational tissue models.
[0492] In one embodiment, computer-aided tissue modeling utilized
in conjunction with certain embodiments for administration of one
or more frozen particle compositions, or frozen piercing implements
includes generating at least one of a two-dimensional plot or a
three-dimensional model. In one embodiment, a two-dimensional plot
or three-dimensional view of anatomical modeling includes one or
more of geometry, morphology, volumetric representation,
mechanical, deformation, kinematic modeling, contour-based
modeling, surface extraction, or solid modeling. In one embodiment,
anatomical modeling occurs by way of computer-assisted tomography
(CAT) or computed tomography (CT) scan, positron emission
tomography (PET) scan, magnetic-resonance imaging (MRI),
ultrasound, electrical-impedance monitoring, x-ray, microscopy,
multiphoton calcium-imaging, or other imaging technique or device.
(See, for example, Girod et al, J. Cranio-Max. Surgery vol. 29, pp.
156-158 (2001), which is incorporated herein by reference.) In one
embodiment, multiple three-dimensional images are assembled or
integrated for modeling of the tissue or organ.
[0493] Computer-aided tissue information utilized in conjunction
with administration of one or more frozen particle compositions, or
frozen piercing implements includes one or more of cell or tissue
classification, hard tissue classification, soft tissue
classification, tumor diagnosis, morphometric or cytometric
information, tumor cell detection, tissue properties, cell
aggregation, cell or tissue growth, cell to cell interaction, or
cell to tissue interaction.
[0494] In one embodiment, at least one computer system is
configured to provide one or more instructions to one or more
devices for deposition or administration of one or more frozen
particle compositions, or frozen piercing implements. In one
embodiment, at least one device is configured to deposit or
administer one or more frozen particle compositions, or frozen
piercing implements on any x, y, or z axis. In one embodiment, the
at least one computer system provides one or more instructions for
predicting, controlling, or varying the administration of one or
more frozen particle compositions, or frozen piercing implements or
deposition of at least one agent included in the one or more frozen
particle compositions, or frozen piercing implements on any x, y,
or z location. In one embodiment, the at least one computer system
provides one or more instructions for temporal, spatial, or
regional locations for deposition or administration of one or more
frozen particle compositions, or frozen piercing implements. Other
components of the at least one computer system or device are
included in the figures as described.
[0495] Computer-aided tissue scaffold design and manufacturing
utilized in conjunction with certain embodiments for administration
of one or more frozen particle compositions, or frozen piercing
implements includes one or more of tissue scaffold modeling,
biomimetic design, tissue scaffold fabrication, hybrid scaffold and
cells, cell pattern, printing and deposition, or blueprint and
organ hierarchical modeling. For example, in one embodiment, at
least one parameter for at least partially constructing, at least
partially reconstructing, or at least partially remodeling at least
one tissue that are considered in design and administration of one
or more frozen particle compositions, or frozen piercing
implements, includes one or more of porosity, pore size,
interconnectivity, transport properties, cell-tissue formation,
mechanical strength, facilitation of attachment or distribution,
growth of regenerative tissue and facilitate the transport of
nutrients or other factors.
[0496] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements are administered to at
least one substrate by way of biopolymer deposition layering. For
example, technology related to a micronozzle-based layered
manufacturing, a microsyringe-based deposition, three dimensional
plotting (e.g., Bioplotter, Envision Tech., Marl, Germany), or
micromolding (e.g., by vacuum-molding) are capable of being
utilized with the one or more frozen particle composition, or
frozen piercing implement deposition. (See, for example, U.S.
Patent Application Publication No. 20060195179.)
[0497] In one embodiment, the reconstructed tissue manufactured by
use of one or more frozen particle compositions, or frozen piercing
implements includes at least one material that mimics natural
structures or functions, or enhances natural tissue growth. For
example, in one embodiment, one or more frozen particle
compositions, or frozen piercing implements are included in "smart"
tissue scaffolds including one or more of a sensor, syringe,
therapeutic agent, electronic article, nano-scale device,
micro-scale device, or feedback mechanism. For example, at least
one biosensor, circuit, or other electronic article can be included
for monitoring tissue growth, dissolution, deterioration,
biochemical function, structural integrity or function,
immunological reaction, or other activities or conditions; or for
providing a feedback mechanism. In one embodiment, the at least one
optical, photonic, or electronic article included in the at least
one tissue or organ is capable of communicating with at least one
computer system.
[0498] In addition, one or more agents are included in one
embodiment of the tissue reconstructed with one or more frozen
particle compositions, or frozen piercing implements. Such agents
include at least one of a therapeutic agent, abrasive, explosive
material, adhesive agent, reinforcement agent, biological
remodeling agent, one or more cells, or other agent. In one
embodiment, the reconstructed or remodeled tissue includes at least
one gene-activated matrix that allows for incorporation of one or
more specific genes when one or more cells are administered to the
matrix, or are allowed to migrate to the matrix. In one embodiment,
one or more frozen particle compositions, or frozen piercing
implements are utilized in three-dimensional cell or organ
printing.
[0499] As described herein, in one embodiment the at least one
biological remodeling agent includes one or more of: scaffolding
materials, cells, nutrients, growth factors, or other components
for at least partially constructing at least one tissue or organ de
novo. See Sun, et al, Ibid.
[0500] In one embodiment, a scaffold is constructed, at least in
part by seeding living cells into the scaffold. As described
herein, various materials are capable of being utilized as a
scaffold by delivering one or more frozen particle compositions, or
frozen piercing implements, or deposition of at least one agent
included in one or more frozen particle compositions, or frozen
piercing implements. In particular, materials including but not
limited to, pastes, resins, gels, bone cements, cellulose,
silicone, polyurethanes, hydrogels, chitosan, or ceramic powders
can be used.
[0501] Also as described herein, one or more materials utilized for
the scaffold can be used for cell seeding, delivery systems for one
or more therapeutic agents, other agents, or for integrating one or
more angiogenic factors, growth factors, cytokines, or other
agents.
[0502] In one embodiment, a composition includes an ex vivo
biological tissue or organ that is at least partially constructed
or at least partially reconstructed by administering one or more
frozen particle compositions, or frozen piercing implements. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements include at least one of a therapeutic agent,
adhesive agent, biological remodeling agent, explosive material,
abrasive, or reinforcement agent.
[0503] In one embodiment, the ex vivo biological tissue or organ is
at least partially constructed or at least partially reconstructed
de novo by administering one or more frozen particle compositions,
or frozen piercing implements. In one embodiment, the one or more
frozen particle compositions, or frozen piercing implements are
administered to at least one substrate. In one embodiment, the at
least one substrate includes one or more of a cell, tissue, organ,
structure, or device. In one embodiment, the composition further
includes at least one article including an optical, photonic, or
electronic article. In one embodiment, the at least one article is
configured to communicate with at least one computer system. In one
embodiment, the at least one article is configured to monitor at
least one characteristic of the at least one biological tissue or
organ. In one embodiment, the at least one characteristic of the at
least one biological tissue or organ includes one or more of:
tissue formation, tissue growth, cell proliferation, cell
differentiation, apoptosis, dissolution, deterioration, nuclear
division, biochemical function of at least one cell, biochemical
function of at least one tissue, biochemical function of at least
one organ, structural integrity, structural function, immunological
reaction, or durability of the at least one biological tissue or
organ. In one embodiment, the at least one characteristic of the at
least one biological tissue or organ includes one or more of:
tissue formation associated with at least one substrate, tissue
growth associated with at least one substrate, cell proliferation
associated with at least one substrate, cell differentiation
associated with at least one substrate, apoptosis associated with
at least one substrate, dissolution associated with at least one
substrate, deterioration associated with at least one substrate,
biochemical function of at least one cell or tissue associated with
at least one substrate, structural integrity of at least one
substrate, structural function of at least one substrate,
immunological reaction to at least one substrate, or durability of
at least one substrate.
[0504] In one embodiment, a composition comprises a support means
for aiding in at least partially constructing or at least partially
reconstructing at least one biological tissue or organ; and one or
more frozen particle compositions, or frozen piercing implements as
described herein. In one embodiment, the one or more frozen
particle compositions, or frozen piercing implements include at
least one biological remodeling agent, adhesive agent, explosive
material, abrasive, reinforcement agent, or therapeutic agent. In
one embodiment, the support means includes at least one substrate
configured for biological tissue formation or tissue growth. In one
embodiment, the support means includes one or more of a cell
scaffold, a tissue scaffold, extracellular matrix, methylcellulose,
agarose, cellulose, a cell, a polymer, or other substrate. In one
embodiment, the support means includes at least one substrate
configured for promoting one or more of: cell migration, cell
attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, diffusion of materials, angiogenesis,
nucleic acid expression, protein translation, protein modification,
protein secretion, carbohydrate production, carbohydrate secretion,
fat production, or fat secretion.
[0505] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements are deposited on a
pre-existing substrate scaffolding, such as a flat or honeycomb
film. See, for example, Nishikawa et al., Mat. Res. Soc. Symp.
Proc. Vol. 724 pp, N11.7.1-N 11.7.6 (2002). In one embodiment, at
least one agent included in one or more frozen particle
compositions, or frozen piercing implements are deposited such that
the scaffolding is formed entirely from such deposition.
[0506] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements include one or more
cells. In one embodiment, the one or more cells are deposited
during administration of the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
one or more frozen particle compositions, or frozen piercing
implements are administered to at least one substrate. In one
embodiment, the one or more cells serve particular functions. In
one embodiment, the one or more cells serve at least one function
including: seeding the scaffold, populating the tissue, reducing an
immune reaction, facilitating tissue function, promoting cellular
or tissue formation, promoting cellular or tissue proliferation,
promoting cellular or tissue differentiation, promoting cellular or
tissue apoptosis, modulating diffusion of materials, or increasing
tissue growth.
[0507] In one embodiment, at least one scaffold, or other substrate
is at least partially generated in at least one of in vitro, in
vivo, ex vivo, in utero, or in planta. In one embodiment, one or
more cells are utilized for seeding at least one scaffold in at
least one of in vitro, in vivo, ex vivo, in utero, or in planta. In
one embodiment, the scaffold or other substrate is at least
partially generated in at least one of in vitro, in vivo, ex vivo,
in utero, or in planta, and subsequently is transplanted or
implanted into at least one subject. In one embodiment, the subject
includes the same subject in which the scaffold or other substrate
was at least partially generated. In one embodiment, wherein the
scaffold or other substrate is transplanted or implanted, the
scaffold or other substrate is modified in vitro, in vivo, ex vivo,
in utero, or in planta prior to transplantation or implantation
into at least one subject. In one embodiment, the at least one
scaffold or at least one remodeled or reconstructed tissue is
transplanted or implanted one or more times. In at least on
embodiment, at least one substrate, including at least one tissue
scaffold, is at least partially generated in vivo, and subsequently
relocated within the same subject. (See, for example, Ripamonti et
al., J. Anat. Vol. 209, pp. 447-468 (2006), which is incorporated
herein by reference.)
[0508] In one embodiment, construction, reconstruction, or
remodeling of at least one biological tissue or organ includes at
least one of designing a blueprint or model. In one embodiment, the
blueprint or model includes a software representation containing
bio-information, graphical representation, physical or material
information, or anatomic or geometric information. In one
embodiment, the blueprint or model includes a process model,
including a software representation that contains the printing
operation control commands, process planning, or toolpath generated
for the blueprint or model and machine hardware and control system.
In one embodiment, the blueprint or model includes a process
machine, including at least one of a hardware representation that
is capable of printing; and a tissue or organ culture system that
is capable of maintaining or growing the printed living biological
tissues. In one embodiment, the three dimensional organ or tissue
printing with one or more frozen particle compositions, or frozen
piercing implements includes at least one of pre-processing or
developing plots or blueprints for the tissue or organ; processing
or actual organ printing; or post-processing or organ conditioning
and accelerated organ maturation.
[0509] In one embodiment, the blueprint or model includes a
description or representation of details of organ anatomy,
morphology, tissue heterogeneity, or vascular systems at different
tissue or organ organizational scales. In one embodiment,
deposition of at least one tissue remodeling agent includes a
process planning program control system. In one embodiment, a
toolpath program is included. In certain instances, the blueprint
or model provides at least one description of the anatomy,
geometry, internal architecture of an organ or tissue of interest
(including tissue heterogeneity), individual tissue geometry and
boundary distinction within the tissue or organ of interest; at
least one definition of vascular networks and three dimensional
topology in an organ of interest; or at least one database of
information based on organ or tissue geometry, heterogeneity, and
vascular network used for toolpath or other program generation of
three-dimensional cell or organ printing.
[0510] In one embodiment, the blueprint or model is constructed
from three dimensional organ anatomy, tomography, or geometry
information provided by medical imaging data (for example, as
provided for by CT, PET, MRI, ultrasound, x-ray, multiphoton
calcium-imaging, or other imaging). Such images can be modified,
simulated, transformed, processed (e.g., electronically processed),
or modeled by a computer system, including by computer program,
such as NURBS, polygonal modeling, or splines and patches modeling.
(See, for example, Sun et al, Ibid.) For example, Boolean, scaling,
Gaussian smoothing, homomorphic filtering, parametric estimation
techniques, Monte Carlo simulations, wavelet based methods,
smoothing, mirroring, gradient weighted partial differential
equation smoothing (PDE), or other operations can be used to modify
a CAD or other design. (See, for example, U.S. Patent Application
Publication No. 20060233454, and U.S. Pat. No. 7,353,153, U.S. Pat.
No. 7,212,958; each of which is incorporated herein by reference.)
In one embodiment, a computer system utilized in at least partial
tissue construction, reconstruction, or remodeling includes at
least one software program interface to convert the CAD design or
device into a heterogeneous material or assembly for formation of
the tissue or organ by deposition of at least one agent included in
one or more frozen particle compositions, or frozen piercing
implements, or administration of one or more frozen particle
compositions, or frozen piercing implements. (See, for example,
U.S. Patent Application Publication No. 20060105011, which is
incorporated herein by reference.) In one embodiment, processing
results include utilizing one or more of algorithmic execution,
logical decision-making, or result prediction.
[0511] In one embodiment, one or more adjacent areas of constructed
or reconstructed tissues or organs include similar biological
remodeling agents. In one embodiment, one or more adjacent areas of
constructed or reconstructed tissues or organs include different
biological remodeling agents. In one embodiment, one or more
substrate scaffolds are utilized to at least partially construct,
at least partially reconstruct, or at least partially remodel at
least one tissue or at least one organ. In one embodiment, the one
or more substrate scaffolds include low microporosity, for strong
structural or mechanical load, while one or more adjacent areas
include high microporosity as well as embedded angiogenic factors,
cytokines, cells, or other agents for seeding the structural
component(s).
[0512] In one embodiment, three-dimensional CAD based models of the
desired tissue are capable of being modified by Boolean operations,
or separated into components or elements that each are
independently exportable to freeform-fabrication technologies. In
one embodiment, heterogeneous blocks are assembled brick-like into
a tissue or organ. In one embodiment, solid structural models are
manufactured out of substrate materials including for example,
quartz or Teflon.RTM.. The models are then infiltrated with
vasculature, living tissue, cells, or other agents. (See, for
example, Sun et al, Ibid.)
[0513] In one embodiment, a method or means for performing the same
includes accepting a first input associated with at least one
characteristic of at least one biological tissue to be at least
partially constructed or at least partially reconstructed;
accepting a second input associated with at least one parameter of
at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions, or frozen piercing
implements including at least one agent; and processing results of
the first input and the second input. In one embodiment, the method
or means for performing the method is implemented by a computer,
including a computer system.
[0514] In one embodiment, the processing results of the first input
and the second input includes electronically processing results of
the first input and the second input. In one embodiment, the
processing results of the first input and the second input includes
electronically processing results of the first input and the second
input by utilizing one or more of Gaussian smoothing, scaling,
homomorphic filtering, parametric estimation techniques, Boolean
operations, Monte Carlo simulations, wavelet based techniques,
mirroring, smoothing, gradient weighted partial differential
equation smoothing, NURBS, polygonal modeling, algorithmic
execution, logical decision-making, result prediction, splines and
patches modeling, or modification of a CAD design.
[0515] In one embodiment, the at least one agent includes one or
more of a therapeutic agent, adhesive agent, abrasive,
reinforcement agent, explosive material, or biological remodeling
agent. In one embodiment, the administering one or more frozen
particle compositions, or frozen piercing implements includes
administering the one or more frozen particle compositions, or
frozen piercing implements to at least one substrate. In one
embodiment, the at least one substrate includes one or more of a
cell, tissue, organ, structure, or device.
[0516] In one embodiment, the first input includes one or more
values related to the at least one characteristic of at least one
biological tissue. In one embodiment, the first input includes one
or more spatial addresses associated with the at least one
characteristic of at least one biological tissue. In one
embodiment, the first input includes one or more of x, y, or z
coordinates associated with the at least one characteristic of at
least one biological tissue. In one embodiment, the at least one
characteristic of at least one biological tissue to be constructed
or reconstructed includes one or more of: morphological feature,
anatomical feature, histological feature, tissue hierarchical
level, scaffold feature, vascular structure feature, heterogenous
tissue feature, mechanical feature, volumetric feature, geometric
feature, volumetric representation, mechanical feature,
deformation, kinematic feature, surface contour feature, cytometric
feature, cell aggregation, cell growth, cell-cell interaction,
cell-tissue interaction, biomimetic design, cell pattern, cell
deposition, organ hierarchical level, tissue microstructure,
cellular microstructure, cell junction feature, tissue junction
feature, cell-tissue classification, hard tissue classification,
soft tissue classification, tumor diagnosis, or other feature.
[0517] In one embodiment, the first input includes one or more
temporal addresses associated with the at least one characteristic
of at least one biological tissue. In one embodiment, the first
input includes one or more values derived from at least one image
of the at least one biological tissue. In one embodiment, the at
least one image includes one or more images acquired by one or more
of laser, holography, x-ray crystallography, optical coherence
tomography, computer-assisted tomography scan, computed tomography,
magnetic resonance imaging, positron-emission tomography scan,
ultrasound, x-ray, electrical-impedance monitoring, microscopy,
spectrometry, flow cytommetry, radioisotope imaging, thermal
imaging, multiphoton calcium-imaging, photography, or in silico
generation.
[0518] In one embodiment, the at least one characteristic of at
least one biological tissue includes one or more of cellular type,
cellular function, cellular size, cellular constitution, cellular
architecture, cellular durability, cellular source, tissue type,
tissue constitution, tissue size, tissue shape, tissue function,
tissue architecture, tissue source, tissue durability, organ type,
organ constitution, organ size, organ shape, organ function, organ
architecture, organ source, or organ durability. In one embodiment,
the at least one biological tissue is located in at least one of in
situ, in vitro, in vivo, in utero, in planta, in silico, or ex
vivo. In one embodiment, the at least one biological tissue is at
least partially located in at least one subject.
[0519] In one embodiment, the method or means for performing the
method further comprises accepting a third input associated with at
least one feature of the at least one subject. In one embodiment,
the at least one feature of the at least one subject includes one
or more of age, gender, genotype, phenotype, proteomic profile, or
health condition.
[0520] In one embodiment, the first input includes one or more
values derived from at least one image of the at least one
biological tissue at least partially located in at least one
subject. In one embodiment, the processing results of the first
input and the second input includes determining at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue with one or more
frozen particle compositions, or frozen piercing implements from
one or more values derived from at least one image of the at least
one biological tissue.
[0521] In one embodiment, the second input includes one or more
values related to the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue by administering one or more frozen particle
compositions, or frozen piercing implements to the at least one
substrate. In one embodiment, the at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue includes one or more of porosity
of the at least one substrate, pore size of the at least one
substrate, interconnectivity of the pores of the at least one
substrate, transport properties of the at least one substrate,
cell-tissue formation of the at least one substrate, mechanical
strength of the at least one substrate, ability for attachment or
distribution of the at least one agent included in the one or more
frozen particle compositions, or frozen piercing implements to the
at least one substrate, ability for attachment or distribution of
one or more cells or tissues to the at least one substrate,
facilitation of at least one nutrient, or tissue formation or
tissue growth associated with the at least one substrate.
[0522] In one embodiment, the one or more values related to the at
least one parameter of constructing or reconstructing the at least
one biological tissue includes one or more predictive values. In
one embodiment, the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue by administering one or more frozen particle
compositions, or frozen piercing implements includes one or more
of: design of plot or model for administration of one or more
frozen particle compositions, or frozen piercing implements,
constitution of the one or more frozen particle compositions, or
frozen piercing implements, formulation of the one or more frozen
particle compositions, or frozen piercing implements, size of the
one or more frozen particle compositions, or frozen piercing
implements, shape of the one or more frozen particle compositions,
or frozen piercing implements, angle of administration of the one
or more frozen particle compositions, or frozen piercing
implements, velocity of administration of the one or more frozen
particle compositions, or frozen piercing implements, quantity of
frozen particle compositions, or frozen piercing implements
administered, rate of administration of more than one frozen
particle composition, spatial location for administration of one or
more frozen particle compositions, or frozen piercing implements,
temporal location for administration of one or more frozen particle
compositions, or frozen piercing implements, method or means for
administration of one or more frozen particle compositions, or
frozen piercing implements, timing of administration of one or more
frozen particle compositions, or frozen piercing implements,
modulation of administration of one or more frozen particle
compositions, or frozen piercing implements, deposition of one or
more frozen particle compositions, or frozen piercing implements,
or rate of deposition of at least one agent.
[0523] In one embodiment, the at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions, or frozen piercing implements includes at
least one parameter relating to at least partially ablating or at
least partially abrading one or more surfaces of the at least one
biological tissue with the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
at least one parameter of at least partially constructing or at
least partially reconstructing the at least one biological tissue
by administering one or more frozen particle compositions, or
frozen piercing implements includes at least one parameter relating
to administering at least one of a therapeutic agent, adhesive
agent, biological remodeling agent, reinforcement agent, abrasive,
or explosive material with the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
spatial location for administration of one or more frozen particle
compositions, or frozen piercing implements includes one or more of
x, y, or z coordinates.
[0524] In one embodiment, the processing results includes comparing
at least one value related to the first input associated with the
at least one characteristic of at least one biological tissue to be
at least partially constructed or at least partially reconstructed
with at least one value related to at least one image of a target
biological tissue. In one embodiment, the image of a target
biological tissue includes an image of a similar biological tissue,
or an image of a dissimilar biological tissue. In one embodiment,
administering one or more frozen particle compositions, or frozen
piercing implements includes depositing the at least one agent on
the at least one substrate. In one embodiment, processing results
includes comparing at least one value related to the second input
associated with the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue with at least one value related to another
administration of one or more frozen particle compositions, or
frozen piercing implements.
[0525] In one embodiment, processing results includes determining
one or more differences in at least one value related to the first
input and at least one value related to at least one image of the
at least one biological tissue or a similar biological tissue. In
one embodiment, processing results includes determining one or more
differences in at least one value related to the second input
associated with the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue and at least one value related to another
administration of one or more frozen particle compositions, or
frozen piercing implements to the at least one substrate. In one
embodiment, processing results includes generating one or more
protocols for administering the one or more frozen particle
compositions, or frozen piercing implements. Other related
embodiments are described in detail herein.
[0526] As described herein, at least one frozen particle
composition or therapeutic composition described herein is useful
in one or more methods or means for performing the method(s),
including one or more of a method for abrasion of at least one
biological tissue surface of a subject by delivering at least one
composition to at least one surface of at least one biological
tissue of a subject in a manner sufficient to abrade the at least
one surface of the at least one biological tissue; a method of
delivering at least one therapeutic agent to at least one
biological tissue; a method of vaccinating a subject; a method of
treating a tissue related to transplantation; a method for cleaning
one or more wounds; a method for oxygenating wounds; a method for
debridement of tissue or cells; a method for removing material from
one or more blood vessel, and others. These and other methods
include utilizing one or more composition or therapeutic
composition described herein.
[0527] In one embodiment, a method of providing at least one agent
to at least one biological tissue of a subject comprises
administering at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device to at least
one biological tissue, wherein the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device includes one or more frozen particles defining at
least one cavity and at least one agent; and the at least one
cavity containing at least one agent.
[0528] In one embodiment, a method of vaccinating a subject
comprises administering to at least one biological tissue of a
subject at least one frozen particle composition, frozen piercing
implement, or frozen piercing implement device, wherein the at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device includes one or more frozen
particles defining at least one cavity; the at least one cavity
containing at least one vaccine. In one embodiment, a method of
vaccinating at least one substrate, such as a biological tissue,
includes administering to the substrate at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device, wherein the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device includes one or more frozen particles defining at
least one cavity; the at least one cavity containing at least one
vaccine.
[0529] In one embodiment, a method of providing at least one frozen
particle composition or frozen piercing implement to at least one
biological tissue of a subject comprises administering at least one
frozen particle composition or frozen piercing implement to at
least one biological tissue, wherein the at least one frozen
particle composition or frozen piercing implement includes one or
more frozen particles including at least one cavity configured for
holding at least one agent.
[0530] In one embodiment, a method for abrasion of at least one
biological tissue surface of a subject includes delivering at least
one composition (frozen particle composition, frozen piercing
implement, etc.) to at least one surface of at least one biological
tissue of a subject in a manner sufficient to abrade the at least
one surface of the at least one biological tissue. As discussed
herein, particular methods are disclosed for abrading or ablating
at least one surface of at least one biological tissue.
[0531] In one particular example, skin abrasion for superficial
resurfacing (e.g., microdermabrasion) can be used to treat acne,
scars, hyperpigmentation, and other skin blemishes, as described
herein. Microscissuining creates microchannels in the skin by
eroding the outer layers of skin with sharp microscopic metal
granules (Carlisle Scientific, Carlisle, Mass.), and Med Pharm Ltd
(Charlbury, UK) has developed a novel dermal abrasion device (D3S)
for the delivery of difficult to formulate therapeutics ranging
from hydrophilic low molecular weight compounds to other
biopharmaceuticals, and can be utilized in conjunction with
administration of at least one composition described herein. See
e.g., Roberts, et al., Clin. Exp. Pharmacol. Physiol. vol. 24, pp.
874-9 (1997); Murthy, et al., J. Controlled Rel. vol. 93, pp. 49-57
(2003); each of which is incorporated herein by reference.
[0532] Abrading at least one surface of at least one biological
tissue may entail debridement of at least one biological tissue. In
certain instances, debridement may include removal or destruction
of dead, damaged, or infected cells or tissues. In certain
instances, debridement can be included as part of an additional
course of treatment (e.g., surgery). In one embodiment, debridement
may include penetrating one or more healthy cells or tissues in
order to facilitate healing. In one embodiment, debridement may
include penetrating one or more healthy cells or tissues near in
proximity to one or more unhealthy cells or tissues of a
subject.
[0533] In one embodiment, one or more of the debridement methods
described herein include penetrating one or more cells or
biological tissues of a subject with at least one frozen particle
composition, frozen piercing implement (or therapeutic
composition), wherein the one or more cells or tissues are
chemically or physically partitioned or segregated from at least
one other part of the tissue or another tissue. In one embodiment,
a method for debridement of at least one biological tissue of a
subject includes delivering at least one frozen particle
composition, frozen piercing implement, or therapeutic composition
to at least one biological tissue of a subject wherein the at least
one biological tissue is partitioned from another biological tissue
or part of another biological tissue, and at least one frozen
particle composition, frozen piercing implement, or therapeutic
composition penetrates the at last one biological tissue with or
without removing any tissue.
[0534] As described herein, in certain instances, a therapeutic
agent is included with the at least one frozen particle composition
to form a therapeutic composition, as described herein. In certain
instances, one or more reinforcement agents or one or more
explosive materials can be included in the at least one frozen
particle composition or therapeutic composition.
[0535] In one embodiment, a method for removing one or more
materials from at least one biological tissue includes delivering
or administering at least one frozen particle composition, frozen
piercing implement, frozen piercing implement device, or
therapeutic composition to the at least one biological tissue. In
one embodiment, the at least one biological tissue includes one or
more tissues described herein. In one embodiment, the one or more
materials may include one or more materials described herein.
[0536] In one embodiment, a method for removing one or more
materials from at least one blood vessel of at least one subject
includes delivering at least one composition to at least one blood
vessel of a subject in a manner sufficient to remove one or more
materials.
[0537] In certain instances, a method for abrasion of at least one
biological tissue or organ surface related to transplantation is
included. In one embodiment, the at least one biological tissue or
organ includes one or more of the biological tissues or organs
described herein.
[0538] In one embodiment, delivering at least one composition to at
least one surface of at least one biological tissue of a subject
includes contacting the at least one surface of at least one
biological tissue of a subject with the composition. In one
embodiment, delivering at least one composition to at least one
surface of at least one biological tissue of a subject includes
contacting the at least one surface of at least one biological
tissue of a subject with the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment,
delivering at least one composition to at least one surface of at
least one biological tissue of a subject includes rupturing one or
more cells of at least one surface of at least one biological
tissue of a subject with the one or more frozen particle
compositions, or frozen piercing implements.
[0539] In one embodiment, a method described herein includes
extracting or collecting material from the at least one abraded
surface of at least one biological tissue. Such extraction or
collection may include the use of at least one vacuum, aspirator,
container, instrument, tool, device, chemical, laser, stylet,
cannula, light source, scope (e.g., laprascope), needle, scalpel,
shunt, stent, bag, film, filter, suction apparatus, tube,
compressed gas, fluid (e.g., fluid stream or mist), magnifying
apparatus, imaging device, vapor deposition, film deposition,
computing device, or system.
[0540] In one embodiment, at least one of the needle, scalpel, or
other tools or instruments utilized in extracting or collecting
material from the at least one cell, tissue, or subject, includes
one or more frozen particle compositions, or frozen piercing
implements (e.g., frozen hydrogen oxide, or other agents as
described herein). Thus, the one or more frozen particle
compositions, or frozen piercing implements are fashioned or molded
for use as microneedles or other instruments (e.g., scapels,
blades, tools, etc.). In one embodiment, the one or more frozen
particle compositions, or frozen piercing implements are
administered prior to, during, or subsequent to surgery. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements are administered during surgery, and just prior
to closing the surgical setting.
[0541] In one embodiment, the extracted or collected material
includes at least one organic or inorganic material. In one
embodiment, the material includes one or more cells from the at
least one abraded surface of at least one biological tissue. In one
embodiment, the at least one material includes at least part of a:
cell, granuloma, eschar, callus, atheromatous plaque, abscess,
pustule, infected tissue, scaling, microorganism, blood clot,
embolus, blood vessel obstruction, duct obstruction, bowel
obstruction, necrotic tissue, stratum corneum, hair follicle,
nevus, wrinkle, keloid, biofilm, calculus, plaque, tartar,
dandruff, keratin, collagen, dust, dirt, metal, glass, hair or fur,
cellular secretion, microorganism, blood cell, blood gas, blood
component, organelle, cell membrane, cell nucleus, particulate
matter, or connective tissue.
[0542] In one embodiment, the at least one material includes at
least one of: enzyme, acid, amino acid, peptide, polypeptide,
protein, oligonucleotide, nucleic acid, ribonucleic acid,
oligosaccharide, polysaccharide, glycopeptide, glycolipid,
lipoprotein, sphingolipid, glycosphingolipid, glycoprotein,
peptidoglycan, lipid, carbohydrate, metalloprotein, proteoglycan,
chromosome, adhesion molecule, cytokine, chemokine, immunoglobulin,
antibody, antigen, platelet, extracellular matrix, blood plasma,
cell wall, hormone, organic compound, inorganic compound, salt, or
cell ligand.
[0543] In one embodiment, the at least one material includes at
least one of: glucose, lactate, urea, uric acid, glycogen, oxygen,
carbon dioxide, carbon monoxide, ketone, nitric oxide, nitrous
oxide, alcohol, alkaloid, opioid, cannabinol, endorphin,
epinephrine, dopamine, serotonin, nicotine, amphetamine,
methamphetamine, anabolic steroid, hydrocodone, hemoglobin,
heparin, clotting factor, tumor antigen, pH, albumin, ATP, NADH,
FADH.sub.2, pyruvate, sulfur, mercury, lead, creatinine,
cholesterol, alpha-fetoprotein, chorionic gonadotropin, estrogen,
progesterone, testosterone, thyroxine, melatonin, calcitonin,
antimullerian hormone, adiponectin, angiotensin, cholecystokinin,
corticotrophin-releasing hormone, erythropoietin, bilirubin,
creatine, follicle-stimulating hormone, gastrin, ghrelin, glucagon,
gonadotropin-releasing hormone, inhibin, growth hormone, growth
hormone-releasing hormone, insulin, human placental lactogen,
oxytocin, orexin, luteinizing hormone, leptin, prolactin,
somatostatin, thrombopoietin, cortisol, aldosterone, estradiol,
estriol, estrone, leukotriene, brain natriuretic peptide,
neuropeptide Y, histamine, vitamin, mineral, endothelin, renin,
enkephalin, DHEA, DHT, alloisoleucine, toxic substance, illegal
substance, therapeutic agent, or any metabolite thereof.
[0544] As indicated herein, in one embodiment, a method for
providing at least one therapeutic agent to at least one biological
tissue of a subject is included. In one embodiment, the at least
one therapeutic agent is delivered to at least one biological
tissue prior to, during, or subsequent to surgery. In certain
instances, at least one therapeutic agent includes one or more
therapeutic agents described herein. In one embodiment, a method of
providing at least one therapeutic agent to at least one biological
tissue of a subject includes delivering at least one composition to
at least one biological tissue, including one or more frozen
hydrogen oxide particles including at least one therapeutic agent;
wherein the at least one composition has at least one crystalline
or amorphous phase.
[0545] As disclosed herein for other embodiments, a method of
vaccinating a subject includes administering at least one
composition that includes at least one vaccine, as well as one or
more abrasives, one or more reinforcement agents, or one or more
explosive materials. In one embodiment, the vaccine described
herein relates to a therapeutic or prophylactic vaccine, and in
certain instances the vaccine relates to an anti-cancer vaccine. In
one embodiment, the one or more abrasives are the same as the one
or more reinforcement agents, or the one or more explosive
materials. In one embodiment, the one or more abrasives are
different than the one or more reinforcement agents. In one
embodiment, the one or more abrasives are different than the one or
more explosive materials.
[0546] In certain instances, for example with at least one vaccine
composition or method relate to vaccinating wildlife animals (e.g.
vaccinating raccoons for rabies, or bison for brucellosis). In
certain instances, the vaccine compositions, and methods described
herein relate to vaccinating domesticated animals (such as cattle,
horses, sheep, or goats). In certain instances, vaccine
compositions and methods described herein relate to vaccinating a
group of subjects, such as a population, a herd, a pride, a gaggle,
a pack, flock, band, cluster, school, brood, troop, colony, or
other group. In certain instances, vaccinating a group of subjects
is included as a route to regulate or control infection within a
group of subjects.
[0547] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements are delivered or
administered to the at least one substrate, such as at least one
biological tissue, in a directed manner such that the tissue is
etched, tattooed, shaped, carved, or otherwise modified. In one
embodiment, the directed manner is predetermined based on
information, such as from the at least one biological tissue, the
subject, the at least one frozen particle composition, the context
of the debridement, the health of the biological tissue, the health
of the subject, or other information.
Frozen Piercing Implements
[0548] In one embodiment, a frozen piercing implement includes one
or more means for piercing at least one substrate, means for
delivering at least one agent to at least one substrate, or means
for sensing or extracting at least one material from at least one
substrate.
[0549] In one embodiment, the frozen piercing implement comprises a
sterile frozen hydrogen oxide implement configured for piercing at
least part of at least one substrate.
[0550] In one embodiment, the sterile frozen hydrogen oxide is
substantially in one or more phases including at least one of
amorphous solid water, low density amorphous ice, high density
amorphous ice, very high density amorphous ice, clathrate ice,
hyperquenched glassy water, ice Ic, ice Ih, ice II, ice III, ice
IV, ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, ice
XII, ice XIII, ice XIV, or ice XV.
[0551] In one embodiment, the frozen piercing implement includes at
least one sterile frozen solution, the solution including at least
one agent; wherein the frozen piercing implement is configured for
piercing at least part of at least one substrate.
[0552] In one embodiment, the frozen piercing implement includes at
least one non-hydrogen oxide frozen solvent; wherein the frozen
piercing implement is configured for piercing at least one
substrate; and wherein the frozen piercing implement is
substantially solid at approximately 65.degree. C., approximately
60.degree. C., approximately 55.degree. C., approximately
50.degree. C., approximately 45.degree. C., approximately
40.degree. C., approximately 37.degree. C., approximately
35.degree. C., approximately 30.degree. C., approximately
25.degree. C., approximately 20.degree. C., approximately
15.degree. C., approximately 10.degree. C., approximately 5.degree.
C., approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween. In
one embodiment, the at least one non-hydrogen-oxide frozen solvent
includes at least one of acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, acetonitrile, hexane,
dichloromethane, methylene chloride, carboxylic acid, saline,
standard saline citrate, methane, toluene, chloroform, or diethyl
ether. In one embodiment, the frozen piercing implement further
comprises at least one of polyethylene glycol, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, HEPES-buffered saline, dextrose, or glucose.
[0553] In one embodiment, the frozen piercing implement, comprises:
at least one sterile frozen component and at least one agent;
wherein the at least one component is substantially in a gaseous
state at or above approximately 0.25 bar, approximately 0.5 bar,
approximately 1.0 bar, approximately 5.0 bar, approximately 10.0
bar, approximately 25 bar, approximately 50 bar, approximately 100
bar, approximately 200 bar, or approximately 500 bar pressure; and
at or above approximately 10.degree. C., approximately 15.degree.
C., approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 37.degree. C.,
approximately 40.degree. C., approximately 45.degree. C., or
approximately 50.degree. C.; and wherein the at least one frozen
piercing implement is configured for piercing at least one
substrate. In one embodiment, the at least one component includes
one or more of nitrogen, helium, neon, xenon, oxygen, air, krypton,
chlorine, bromine, or argon.
[0554] In one embodiment, the frozen piercing implement has at
least one major dimension of approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer, or any value therebetween. In
one embodiment, the frozen piercing implement is substantially in
the form of one or more frozen particles. In one embodiment, the at
least one major dimension includes at least one of a radius,
diameter, length, width, height, or perimeter.
[0555] In one embodiment, the frozen piercing implement is
configured for delivering at least one agent to the at least one
substrate. As described herein, the at least one agent includes at
least one of a therapeutic agent, explosive material, reinforcement
agent, adhesive agent, biological remodeling agent, or abrasive. In
one embodiment, the at least one agent includes at least one of a
nontoxic, biocompatible, bioresorbable, or biodegradable agent. In
one embodiment, the at least one agent includes at least one
sterile or sterilizing agent. In one embodiment, the at least one
sterilizing agent includes at least one antimicrobial compound. In
one embodiment, the at least one sterilizing agent includes at
least one antiseptic. In one embodiment, the at least one agent is
included as an outer coating of the frozen piercing implement. In
one embodiment, the at least one agent is encapsulated within the
frozen piercing implement. In one embodiment, the at least one
agent is included as part of a carrier that assists in synthesis or
activation of the at least one agent. In one embodiment, the at
least one agent includes one or more components that are inactive.
In one embodiment, the one or more components are configured to be
activated by administration. In one embodiment, the at least one
agent includes one or more of a prodrug or precursor compound.
[0556] In one embodiment, the frozen piercing implement is
substantially solid at approximately 0.degree. C., approximately
-10.degree. C., approximately -20.degree. C., approximately
-30.degree. C., approximately -40.degree. C., approximately
-50.degree. C., approximately -60.degree. C., approximately
-70.degree. C., approximately -75.degree. C., approximately
-80.degree. C., approximately -85.degree. C., approximately
-90.degree. C., approximately -95.degree. C., approximately
-100.degree. C., approximately -120.degree. C., approximately
-150.degree. C., approximately -180.degree. C., approximately
-200.degree. C., approximately -220.degree. C., approximately
-250.degree. C., or any temperature less than or therebetween.
[0557] In one embodiment, the frozen piercing implement includes at
least one cavity. In one embodiment, at least one agent is located
in the at least one cavity. In one embodiment, the frozen piercing
implement includes at least two different agents configured to
combine upon administration of the frozen piercing implement. In
one embodiment, the at least two different agents are configured to
react upon administration of the frozen piercing implement. In one
embodiment, the at least two different agents are configured to act
cooperatively or synergistically upon administration of the frozen
piercing implement.
[0558] In one embodiment, the frozen piercing implement further
comprises at least one detection material. As described herein, in
one embodiment, the detection material includes at least one of a
contrast agent, sensor, or electronic identification device. In one
embodiment, the at least one electronic identification device
includes at least one radio frequency identification device. In one
embodiment, the detection material includes at least one of a
radioactive, luminescent, colorimetric or odorous substance. In one
embodiment, the at least one radioactive, luminescent, colorimetric
or odorous substance includes at least one temperature-sensitive
substance. In one embodiment, the detection material includes at
least one of a diamagnetic particle, ferromagnetic particle,
paramagnetic particle, super paramagnetic contrast agent, particle
with altered isotope, or other magnetic particle.
[0559] In one embodiment, the frozen piercing implement includes at
least one conduit configured to deliver at least one electrical
charge, electromagnetic energy, or other substances. In one
embodiment, the frozen piercing implement includes one or more
cavities or channels. The cavity can be in the form of a pit, pore,
core, coating, or other area of concentration.
[0560] In one embodiment, the at least one channel extends across
at least one major dimension of the at least one frozen piercing
implement. In one embodiment, the at least one channel includes at
least one of an organic or inorganic small molecule, clathrate or
caged compound, protocell, coacervate, microsphere, Janus particle,
proteinoid, laminate, helical rod, liposome, macroscopic tube,
niosome, sphingosome, toroid, vesicular tube, vesicle, small
unilamellar vesicle, large unilamellar vesicle, large multilamellar
vesicle, multivesicular vesicle, lipid layer, lipid bilayer,
micelle, organelle, cell, membrane, nucleic acid, peptide,
polypeptide, protein, glycopeptide, glycolipid, lipoprotein,
sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan,
lipid, carbohydrate, metalloprotein, proteoglycan, chromosome,
nucleus, acid, support structure, buffer, protic solvent, aprotic
solvent, nitric oxide, nitrous oxide, nitric oxide synthase, amino
acid, micelle, polymer, copolymer, monomer, prepolymer, cell
receptor, adhesion molecule, cytokine, chemokine, immunoglobulin,
antibody, antigen, platelet, extracellular matrix, blood, plasma,
cell ligand, zwitterionic material, cationic material,
oligonucleotide, nanotube, piloxymer, transfersome, gas, element,
contaminant, radioactive particle, hormone, microorganism,
bacteria, virus, quantum dot, contrast agent, or any part thereof.
In one embodiment, a method comprises sensing or extracting at
least one material from the at least one substrate. Thus, the at
least one frozen piercing implement or frozen particle composition
can include methods for chemical testing of a subject (e.g.,
pharmaceutical drugs, illicit drugs, toxins or poisons, biochemical
disorders, or dietary deficiencies, etc.).
[0561] In one embodiment, the at least one channel is configured to
deliver at least one agent or at least one detection material to
the at least one substrate. In one embodiment, the at least one
channel is configured to deliver at least one agent, or detection
material by at least one of: van der Waals forces, gravitational
force, electrostatic energy, hydration attraction, hydration
repulsion, hydrophobic attraction, hydrophobic repulsion,
diffusion, osmosis, mechanical pump, electroosmosis,
electrophoresis, convection, sublimation, hydroloysis, magnetic
attraction or repulsion, capillary action, pressure gradient,
concentration gradient, electricity, ultrasound, receptor binding,
heat, chemical, chemical reaction, tunablemicrolens or nanolens,
gate or valve, or external applied force.
[0562] In one embodiment, the external applied force includes one
or more of physical propulsion, thermal displacement, laminar flow,
turbulent flow, x-rays, gamma rays, electron beams, proton beams,
or acoustic droplet ejection. In one embodiment, the at least one
channel of the frozen piercing implement contains at least one
agent. In one embodiment, the at least one channel of the frozen
piercing implement contains at least one of an ion exchange
material, ion selective material, permeable material, solid
material, or semi-permeable material. In one embodiment, the wall
thickness of the at least one channel is approximately 1 nm,
approximately 10 nm, approximately 50 nm, approximately 100 nm,
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 .mu.m, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, or any value therebetween.
In one embodiment, at least one surface of the at least one channel
is substantially hydrophobic. In one embodiment, at least one
surface of the at least one channel is substantially
hydrophilic.
[0563] In one embodiment, the at least one frozen piercing
implement includes one or more layers. In one embodiment, the at
least one frozen piercing implement includes at least one layer of
a different constitution than at least one other layer. In one
embodiment, the frozen piercing implement approximates the shape of
at least one of a sphere, bullet, flechette, cone, frustum, needle,
arrow, spear, diamond, pyramid, cylinder, minie ball, shuttlecock,
spiral, bell, pear, crystal, cube, spheroid, tetrahedron, crescent,
possesses a high aspect ratio shape, or any combination thereof. In
one embodiment, the frozen piercing implement possesses a high
aspect ratio shape from largest to smallest dimension of greater
than or approximately equal to 1.1, greater than or approximately
equal to 1.5, greater than or approximately equal to 2.0, greater
than or approximately equal to 3.0, greater than or approximately
equal to 5.0, greater than or approximately equal to 10.0, greater
than or approximately equal to 20.0, greater than or approximately
equal to 50.0, greater than or approximately equal to 100.0,
greater than or approximately equal to 1000.0, or any value
therebetween.
[0564] In one embodiment, the at least one implement is configured
to melt or evaporate prior to, during, or subsequent to contacting
the at least one substrate. In one embodiment, the at least one
implement is configured to melt within the at least one substrate.
In one embodiment, the at least one implement is configured to be
substantially removed from the at least one substrate. In one
embodiment, the at least one implement is configured to penetrate
at least an outer surface layer of the at least one substrate.
[0565] In one embodiment, the frozen piercing implement includes at
least a portion of a piercing instrument. In one embodiment, the
frozen piercing implement includes at least approximately 5%,
approximately 10%, approximately 20%, approximately 30%,
approximately 40%, approximately 50%, approximately 60%,
approximately 70%, approximately 80%, approximately 90%,
approximately 100%, or any value less than or therebetween portion
of a piercing instrument. In one embodiment, the piercing
instrument includes at least one of metal, wood, plastic,
fiberglass, or other material. In one embodiment, the piercing
instrument includes at least one solid internal portion. In one
embodiment, the at least one solid internal portion is sterile. In
one embodiment, the implement includes at least one solid internal
portion and at least one sterile frozen hydrogen oxide external
coating. In one embodiment, the frozen external coating is
configured to melt or evaporate prior to, during, or subsequent to
piercing the at least one substrate. In one embodiment, the at
least one solid internal portion is configured to be removed from
the at least one substrate. In one embodiment, the at least one
implement is configured to break off within the at least one
substrate. In one embodiment, the at least one implement is
configured to break off due to an applied load. In one embodiment,
the at least one implement is configured to break off due to
thermal input. In one embodiment, the thermal input includes at
least one thermal input from at least one internal or external
source. In one embodiment, the at least one external source
includes the at least one substrate. In one embodiment, the at
least one implement is configured to break off due to at least one
weak portion of the implement.
[0566] In one embodiment, the frozen piercing implement further
includes at least one non-frozen implement holding device. In one
embodiment, the at least one non-frozen implement holding device
includes at least one handle, robotic arm, or surgical device. In
one embodiment, the frozen piercing implement is approximately
solid. In one embodiment, the frozen piercing implement is
approximately semi-permeable. In one embodiment, the frozen
piercing implement includes one or more pits or ports. In one
embodiment, the frozen piercing implement includes at least one
substantially tapered end. In one embodiment, the at least one
substantially tapered end includes an angle of approximately
30.degree., approximately 40.degree., approximately 50.degree.,
approximately 60.degree., approximately 70.degree., approximately
80.degree., approximately 90.degree., or any value therebetween or
greater. In one embodiment, the angle includes a wall angle.
[0567] In one embodiment, the frozen piercing implement includes at
least one substantially beveled end. In one embodiment, the at
least one substantially beveled end includes an angle of
approximately 30.degree., approximately 40.degree., approximately
50.degree., approximately 60.degree., approximately 70.degree.,
approximately 80.degree., approximately 90.degree., or any value
therebetween or greater. In one embodiment, the angle includes a
wall angle. In one embodiment, the frozen piercing implement
includes at least one substantially jagged or substantially serated
end. In one embodiment, the frozen piercing implement substantially
approximates at least one projection. In one embodiment, the at
least one projection substantially terminates in at least one tip.
In one embodiment, the at least one tip is substantially hollow. In
one embodiment, a substantially jagged or serated end includes
multiple protrusions or peaks. In one embodiment, the serated or
substantially jagged end allows for increased substrate
penetration, increased substrate ablation or abrasion, increased
end surface area, or increased carrying capacity for at least one
agent. See, for example, U.S. Pat. No. 5,457,041, which is
incorporated herein by reference.
[0568] In one embodiment, the radius of the at least one tip is
approximately 1 nm, approximately 10 nm, approximately 100 nm,
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 gm, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, or any value
therebetween.
[0569] In one embodiment, the radius of curvature of the tip is
approximately 1 nm, approximately 10 nm, approximately 100 nm,
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 50 .mu.m, approximately 100 .mu.m,
approximately 500 .mu.m, approximately 1 mm, approximately 5 mm, or
any value therebetween. In one embodiment, the frozen piercing
implement includes at least one port. In one embodiment, the at
least one port includes at least one side port. In one embodiment,
the at least one port includes at least one end port. In one
embodiment, the at least one port includes at least one inlet port.
In one embodiment, the at least one inlet port is in fluid
communication with at least one channel. In one embodiment, the at
least one port includes at least one outlet port. In one
embodiment, the at least one outlet port is in fluid communication
with at least one channel. In one embodiment, the at least one port
includes at least one inlet port in fluid communication with at
least one outlet port.
[0570] In one embodiment, the frozen piercing implement is
formulated to be administered to the at least one substrate. In one
embodiment, the at least one substrate includes one or more of a
cell, tissue, organ, structure, device, or food product. In one
embodiment, the at least one substrate includes at least one food
product.
[0571] In one embodiment, the frozen piercing implement is
configured to pierce at least one substrate to a depth of
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 .mu.m, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, or any value therebetween.
In one embodiment, the at least one frozen piercing implement is
configured to abrade or ablate at least one substrate surface. In
one embodiment, the plurality of frozen piercing implements is
positioned such that each frozen piercing implement of the array
device contacts a single cell of at least one biological
tissue.
[0572] In one embodiment, the piercing includes abrading or
ablating at least a portion of the surface of the at least one
substrate. In one embodiment, the piercing includes abrading or
ablating one or more cells or tissues.
[0573] In one embodiment, the at least one frozen piercing
implement includes at least one sensor. In one embodiment, the at
least one sensor includes at least one sensor configured for
detecting at least one of a biochemical, electrical, optical,
functional, physical, chemical, biological, or structural
characteristic of the at least one material. In one embodiment, the
at least one frozen piercing implement is configured for extracting
at least one material from the at least one substrate. In one
embodiment, the at least one material includes one or more of a
cell, organic or inorganic small molecule, vesicle, micelle,
organelle, cell membrane, nucleic acid, peptide, polypeptide,
protein, oligosaccharide, polysaccharide, glycopeptide, glycolipid,
lipoprotein, sphingolipid, glycosphingolipid, glycoprotein,
peptidoglycan, lipid, carbohydrate, metalloprotein, proteoglycan,
chromosome, cell nucleus, amino acid, polymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
transfersome, gas, element, contaminant, radioactive particle,
hormone, or any part thereof.
[0574] In one embodiment, the at least one frozen piercing
implement is configured for extracting at least one material from
the at least one substrate by at least one of: van der Waals
forces, gravitational pull, electrostatic energy, hydration
attraction, hydration repulsion, hydrophobic attraction,
hydrophobic repulsion, magnetic attraction, magnetic repulsion,
capillary action, or external applied force. In one embodiment, the
frozen piercing implement further comprises at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, glycopeptide, glycolipid, lipoprotein, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus,
acid, support structure, buffer, protic solvent, aprotic solvent,
nitric oxide, nitrous oxide, nitric oxide synthase, amino acid,
micelle, polymer, copolymer, monomer, prepolymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
nanotube, piloxymer, transfersome, gas, element, contaminant,
radioactive particle, hormone, microorganism, bacteria, virus,
quantum dot, contrast agent, or any part thereof.
[0575] In one embodiment, the frozen piercing implement includes
one or more of nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[0576] In one embodiment, a plurality of frozen piercing implements
is disclosed. In one embodiment, the frozen piercing implement is
included in at least one frozen piercing implement device. In one
embodiment, the at least one frozen piercing implement device
includes at least one of a frozen piercing implement array device,
frozen piercing implement fluidic device, or frozen piercing
implement injection device. In one embodiment, the frozen piercing
implement device includes at least one of a patch, bandage, shunt,
wound dressing, splint, computer mouse, telephone, mobile phone,
writing instrument, article of clothing, blanket, pen-type device,
other article of manufacture, or medical instrument. In one
embodiment, the frozen piercing implement device includes at least
one cooling element. In one embodiment, the at least one cooling
element includes one or more of a refrigeration mechanism, heat
exchanger, thermoelectric, cold plate, low temperature thermal
ballast, or phase change material.
[0577] In one embodiment, the frozen piercing implement includes
one or more of a suspension, mixture, solution, sol, clathrate,
colloid, emulsion, microemulsion, aerosol, ointment, capsule,
powder, tablet, suppository, cream, device, paste, resin, liniment,
lotion, ampule, elixir, spray, syrup, tincture, detection material,
polymer, biopolymer, buffer, adjuvant, diluent, lubricant,
disintegration agent, suspending agent, solvent, light-emitting
agent, colorimetric agent, glidant, anti-adherent, anti-static
agent, surfactant, plasticizer, emulsifying agent, flavor, gum,
sweetener, coating, binder, filler, compression aid, encapsulation
aid, preservative, granulation agent, spheronization agent,
stabilizer, adhesive, pigment, sorbent, nanoparticle, or gel. In
one embodiment, the frozen piercing implement further comprises at
least one pharmaceutically-acceptable carrier or excipient.
[0578] In one embodiment, the frozen piercing implement is
substantially in the form of at least one blade. In one embodiment,
the at least one blade is at least part of one or more of a knife,
razor, scissors, hatchet, saw, rotary device, or scalpel. In one
embodiment, the at least one frozen piercing implement is
configured as a tweezers, fork, scriber, graver, spade, screw,
needle or pin. In one embodiment, the needle or pin include at
least one macroneedle, macropin, microneedle, micropin, nanoneedle,
or nanopin. In one embodiment, the frozen piercing implement is
formulated to be administered by one or more of topical
administration, oral administration, enteral administration,
mucosal administration, percutaneous administration, or parenteral
administration. In one embodiment, the frozen piercing implement is
formulated to be administered by high velocity impact. In one
embodiment, the frozen piercing implement is formulated to be
administered by one or more devices.
[0579] In certain instances, the frozen piecing implement is
utilized in compositions or methods for delivery of at least one
agent, including but not limited to a therapeutic agent, adhesive
agent, reinforcement agent, biological remodeling agent, explosive
material, or abrasive.
[0580] In one embodiment, the frozen piercing implementation is
utilized in compositions or methods for transdermal therapeutic
agent delivery, including but not limited to vaccine delivery.
[0581] In one embodiment, the frozen piercing implements or tools
are utilized in compositions or methods for electrotherapy, nucleic
acid sampling, protein sampling, cell sampling, tissue sampling,
nucleic acid analysis, protein analysis, cell analysis, tissue
analysis, iontophoresis, or other technique. In one embodiment, the
at least one frozen piercing implement includes at least one of a
channel, pump, sensor, injector, actuator, heater, detector,
controller, transducer, receiver, transmitter, circuit, lens,
tunable lens, valve, gate, nanoparticle, microparticle, power
source, or detection material. In one embodiment, the frozen
piercing implement includes at least one waveguide that provides a
path to guide energy waves.
[0582] In one embodiment, the frozen piercing implement includes a
length of approximately 1 .mu.m, approximately 5 .mu.m,
approximately 10 .mu.m, approximately 15 .mu.m, approximately 20
.mu.m, approximately 50 .mu.m, approximately 100 .mu.m,
approximately 120 .mu.m, approximately 150 .mu.m, approximately 200
.mu.m, approximately 250 .mu.m, approximately 300 .mu.m,
approximately 350 .mu.m, approximately 400 .mu.m, approximately 450
.mu.m, approximately 500 .mu.m, approximately 600 .mu.m,
approximately 700 .mu.m, approximately 800 .mu.m, approximately 900
.mu.m, approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, approximately 10 mm,
approximately 20 mm, approximately 30 mm, approximately 40 mm,
approximately 50 mm, approximately 60 mm, approximately 70 mm,
approximately 80 mm, approximately 90 mm, approximately 100 mm,
approximately 200 mm, approximately 300 mm, approximately 400 mm,
approximately 500 mm, approximately 600 mm, approximately 700 mm,
approximately 800 mm, approximately 900 mm, approximately 1 cm,
approximately 10 cm, approximately 20 cm, or any value
therebetween.
[0583] In one embodiment, the frozen piercing implement has a
substantially solid form.
[0584] In one embodiment, the frozen piercing implement has a
substantially semi-permeable form. In one embodiment, the frozen
piercing implement includes at least one channel, providing the
frozen piercing implement with at least one inner diameter and at
least one outer diameter.
[0585] In one embodiment, the frozen piercing implement includes an
outer diameter of approximately 1 nm, approximately 10 nm,
approximately 100 nm, approximately 1 .mu.m, approximately 5 .mu.m,
approximately 10 .mu.m, approximately 15 .mu.m, approximately 20
.mu.m, approximately 50 .mu.m, approximately 100 .mu.m,
approximately 120 .mu.m, approximately 150 .mu.m, approximately 200
.mu.m, approximately 250 .mu.m, approximately 300 .mu.m,
approximately 350 .mu.m, approximately 400 .mu.m, approximately 450
.mu.m, approximately 500 .mu.m, approximately 600 .mu.m,
approximately 700 .mu.m, approximately 800 .mu.m, approximately 900
.mu.m, approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, approximately 10 mm,
approximately 20 mm, approximately 30 mm, approximately 40 mm,
approximately 50 mm, approximately 60 mm, approximately 70 mm,
approximately 80 mm, approximately 90 mm, approximately 100 mm,
approximately 200 mm, approximately 300 mm, approximately 400 mm,
approximately 500 mm, approximately 600 mm, approximately 700 mm,
approximately 800 mm, approximately 900 mm, approximately 1 cm,
approximately 10 cm, or any value therebetween.
[0586] In one embodiment, the frozen piercing implement has an
inner diameter, and includes an inner diameter of approximately 1
nm, approximately 10 nm, approximately 100 nm, approximately 1
.mu.m, approximately 5 .mu.m, approximately 10 .mu.m, approximately
15 .mu.m, approximately 20 .mu.m, approximately 50 .mu.m,
approximately 100 .mu.m, approximately 120 .mu.m, approximately 150
.mu.m, approximately 200 .mu.m, approximately 250 .mu.m,
approximately 300 .mu.m, approximately 350 .mu.m, approximately 400
.mu.m, approximately 450 .mu.m, approximately 500 .mu.m,
approximately 600 .mu.m, approximately 700 .mu.m, approximately 800
.mu.m, approximately 900 .mu.m, approximately 1 mm, approximately 2
mm, approximately 3 mm, approximately 4 mm, approximately 5 mm,
approximately 10 mm, approximately 20 mm, approximately 30 mm,
approximately 40 mm, approximately 50 mm, approximately 60 mm,
approximately 70 mm, approximately 80 mm, approximately 90 mm,
approximately 100 mm, approximately 200 mm, approximately 300 mm,
approximately 400 mm, approximately 500 mm, approximately 600 mm,
approximately 700 mm, approximately 800 mm, approximately 900 mm,
approximately 1 cm, approximately 10 cm, or any value
therebetween.
[0587] In one embodiment, a single frozen piercing implement
pierces a single cell. In one embodiment, a single frozen piercing
implement pierces multiple cells. In one embodiment, a single
frozen piercing implement pierces at least one biological tissue.
Most cells in an animal, such as a human, are approximately 10-30
.mu.m in diameter, while most plant and fungal cells are
approximately 10-100 .mu.m in diameter. Thus, in one embodiment, at
least one of the inner or outer diameter is configured in size
according to the targeted cell(s).
[0588] In one embodiment, the pressure exerted on a substrate is
adjusted for use of one or more frozen piercing implements. In one
embodiment, the pressure exerted on a substrate is increased or
decreased in order to adjust the rate of melting, sublimation,
evaporation, transformation, activation, etc. of the one or more
frozen piercing implements or a component thereof.
[0589] In one embodiment, the frozen piercing implement is
configured to pierce or penetrate at least one substrate. In at
least one embodiment, at least a portion of the at least one
substrate includes skin or surface of a tissue, organ, or subject's
body. In one embodiment, the frozen piercing implement is
configured to pierce or penetrate at least a portion of the stratum
corneum, epidermis, or dermis layer of the skin. In one embodiment,
the frozen piercing implement is administered prior to, during, or
subsequent to surgery.
[0590] In one embodiment, the at least one frozen piercing
implement is configured to substantially form at least one blade.
In one embodiment, the at least one blade is at least part of one
or more of a knife, razor, scissors, hatchet, saw, rotary device,
or scalpel. In one embodiment, the at least one frozen piercing
implement is configured as a tweezers, fork, scriber, graver,
spade, needle or pin. In one embodiment, the needle or pin include
at least one macroneedle, macropin, microneedle, micropin,
nanoneedle, or nanopin.
[0591] The epidermis layer of the skin is approximately 100-150
.mu.m thick, and includes an outermost layer, the stratum corneum,
which is approximately 10-15 .mu.m in thickness. In certain areas,
the blood vessels are generally present more superficially than
nerves, which allows for delivery of at least one agent, or
extraction of at least one material from the skin and underlying
tissue, largely without activating the nerves and signaling pain.
See, e.g., Kumar and Philip, Trop. J. Pharm Res. 6(1):633-644
(2007), which is incorporated herein by reference. In certain
instances, it is desirable to penetrate the epidermis and/or dermis
layer of the skin in order to deliver at least one agent (including
but not limited to a therapeutic agent) to a subcutaneous,
intravenous, or other location beneath the skin. In one embodiment,
the frozen piercing implement is configured to deliver at least one
agent beneath the surface of the skin or outer covering of the
tissue, organ, or subject's body. In one embodiment, the frozen
piercing implement is configured to pierce or penetrate the skin
largely without activating nerves beneath the skin.
[0592] In one embodiment, the frozen piercing implement includes at
least one functionalized surface. In one embodiment, the
functionalized surface includes one or more functional groups
including but not limited to at least one of a binding group (e.g.,
coupling agents, and the like), a linking group (e.g., spacer
groups, organic spacer groups, and the like), or a matrix-forming
group. Some examples of binding groups include but are not limited
to at least one acrylate, alkoxysilane, alkyl thiol, arene, azido,
carboxylate, chlorosilane, alkoxysilane, acetocysilane, silazane,
disilazane, disulfide, epoxide, ester, hydrosilyl, isocyanate,
phosphoamidite, isonitrile, methacrylate, nitrene, nitrile,
quinone, silane, sulfhydryl, thiol, vinyl group, and the like. Some
examples of linking groups include but are not limited to at least
on dendrimer, polymer, hydrophilic polymer, hyperbranched polymer,
poly(amino acid), polyacrylamide, polyacrylate, polyethylene
glycol, polyethylenimine, polymethacrylate, polyphosphazene,
carbohydrate, monosaccharide, disaccharide, polysaccharide,
polysiloxane, polystyrene, polyurethane, propylene, amino acid,
nucleic acid, polypeptide, protein, copolymer, block copolymer, and
the like. Some examples of matrix-forming groups include but are
not limited to at least one dendrimer polyamine polymer, bovine
serum albumin, casein, glycolipid, lipid, heparin,
glycosaminoglycan, mucin, surfactant, polyoxyethylene-based
surface-active substance (e.g., polyoxyethlene-polyoxypropylene
copolymer, polyoxyethylene 12 tridecyl ether, polyoxyethylene 18
tridecyl ether, polyoxyethylene 6 tridecyl ether, polyoxyethylene
sorbitan tetraoleate, polyoxyethylene sorbitol hexaoleate, and the
like) polyethylene glycol, saccharide, polysaccharide, serum
dilution, and the like.
[0593] In one embodiment, the one or more functional groups include
charged functional groups capable of maintaining a positive or
negative charge over a wide range of pH. Some examples of charged
functional groups include but are not limited to at least one
cation, anion, amine, acid, halocarbon, sulfonic acid, quaternary
amine, metal, --NH.sub.3.sup.+, --COOH, --COO--, --SO.sub.3,
CH.sub.2N.sup.+(CH.sub.3).sub.3, and the like.
[0594] In one embodiment, the one or more frozen piercing
implements are tested for constitution, physical structure,
physical integrity, or other property. In one embodiment, the one
or more frozen piercing implements are designed with assistance
from at least one computer program or computing device.
[0595] In one embodiment, a method of administering at least one
frozen piercing implement to at least one substrate comprises
contacting at least one frozen piercing implement with at least one
substrate, wherein the at least one frozen piercing implement
includes sterile frozen hydrogen oxide and at least one agent; and
wherein the frozen piercing implement has at least one major
dimension of approximately one centimeter or less, approximately
one millimeter or less, approximately one micrometer or less,
approximately one nanometer or less, or any value therebetween.
[0596] In one embodiment, wherein administering the at least one
frozen piercing implement to at least one substrate includes
propelling, ejecting, or accelerating the at least one frozen
piercing implement toward the at least one substrate at a
predetermined angle, a predetermined velocity, a predetermined rate
of administration, a predetermined depth, a predetermined location,
a predetermined time sequence, or a predetermined spatial pattern.
In one embodiment, the method further comprises varying the rate,
velocity, or angle at which the at least one frozen piercing
implement is administered to the at least one substrate. In one
embodiment, the method includes administering the at least one
frozen piercing implement to at least one substrate by propelling,
ejecting, or accelerating a plurality of frozen piercing implements
toward the at least one substrate.
[0597] In one embodiment, the frozen piercing implement is
configured to pierce or penetrate at least one substrate. Certain
examples of substrates are provided herein. In one embodiment, the
temperature of the substrate is adjusted prior to, during, or
subsequent to administration of one or more frozen piercing
implements. In one embodiment, the temperature of the substrate is
increased or decreased in order to adjust the rate, for example, of
melting, sublimation, evaporation, transformation, activation, etc.
of the one or more frozen piercing implements or a component
thereof. In one embodiment, the method further comprises adjusting
the temperature of the at least one substrate prior to, during, or
subsequent to administering the one or more frozen piercing
implements to at least approximately 37.degree. C., approximately
36.degree. C., approximately 35.degree. C., approximately
34.degree. C., approximately 33.degree. C., approximately
32.degree. C., approximately 31.degree. C., approximately
30.degree. C., approximately 29.degree. C., approximately
28.degree. C., approximately 27.degree. C., approximately
26.degree. C., approximately 25.degree. C., approximately
24.degree. C., approximately 23.degree. C., approximately
22.degree. C., approximately 21.degree. C., approximately
20.degree. C., approximately 19.degree. C., approximately
18.degree. C., approximately 17.degree. C., approximately
16.degree. C., approximately 15.degree. C., approximately
14.degree. C., approximately 13.degree. C., approximately
12.degree. C., approximately 11.degree. C., approximately
10.degree. C., approximately 9.degree. C., approximately 8.degree.
C., approximately 7.degree. C., approximately 6.degree. C.,
approximately 5.degree. C., approximately 4.degree. C.,
approximately 3.degree. C., approximately 2.degree. C.,
approximately 1.degree. C., approximately 0.degree. C., or any
temperature therebetween.
[0598] In one embodiment, contacting at least one substrate
includes at least one of cutting, stitching, cauterizing, freezing,
perforating, penetrating, ablating, or abrading at least a part of
the surface of the at least one substrate. In one embodiment,
administering the at least one substrate occurs in conjunction with
cryosurgery, cryotherapy, or mesotherapy.
[0599] In one embodiment, contacting at least one substrate affects
one or more of electrical resistance of the at least one substrate,
or permeability of the at least one substrate. In one embodiment,
at least one frozen piercing implement is administered to at least
one substrate as party of a method for vaccination. In one
embodiment, a method of vaccinating a subject comprises
administering at least one frozen piercing implement or frozen
particle composition described herein.
Frozen Piercing Implement Devices
[0600] In one embodiment, at least one frozen piercing implement or
frozen particle composition (including a therapeutic composition)
is utilized to fabricate at least one device. In one embodiment,
the frozen piercing implement device includes at least one array
device, fluidic device, or injection device. In one embodiment, the
frozen piercing implement device includes at least one of a patch,
bandage, shunt, wound dressing, splint, computer mouse, telephone,
mobile phone, writing instrument, article of clothing, blanket,
pen-type device, other article of manufacture, or medical
instrument.
[0601] In one embodiment, a fluidic device, comprises: a support
structure at least partially defining at least one compartment; and
at least one frozen piercing implement in fluid communication with
the at least one compartment; wherein the at least one frozen
piercing implement has at least one major dimension of
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer or less, or any value therebetween.
[0602] In one embodiment, an array device, comprises: a support
structure having a surface; and a plurality of sterile frozen
piercing implements extending substantially outward from the
support structure. In one embodiment, the plurality of sterile
frozen piercing implements having at least one major dimension of
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer or less, or any value therebetween.
[0603] In one embodiment, an array device comprises: a support
structure having a surface; a plurality of piercing implements
extending substantially outward from the surface of the support
structure; wherein at least one piercing implement of the plurality
of piercing implements includes a frozen piercing implement. In one
embodiment, the at least one frozen piercing implement has at least
one major dimension of approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer or less, or any value
therebetween.
[0604] In one embodiment, a composition, comprises: a plurality of
piercing implement array devices joined together, the piercing
implement array devices including at least one frozen piercing
implement.
[0605] In one embodiment, a composition, comprises: a support means
for an array device; wherein the array device includes one or more
frozen piercing implements.
[0606] In one embodiment, the plurality of sterile frozen piercing
implements have at least one major dimension of approximately one
centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer,
or any value therebetween. In one embodiment, the plurality of
sterile frozen piercing implements extends substantially
perpendicular to the support structure. In certain instances, the
frozen piercing implements extend through the support structure, or
from the surface of the support structure. In one embodiment, the
support structure itself includes at least one frozen composition.
In one embodiment, the support structure includes at least one
frozen composition also included in at least one frozen piercing
implement. In one embodiment, the support structure is at least
partially frozen. In one embodiment, the support structure and at
least one frozen piercing implement of the plurality of frozen
piercing implements include at least one common constituent.
[0607] In one embodiment, the plurality of frozen piercing
implements are positioned substantially parallel to each other. In
one embodiment, the plurality of frozen piercing implements are
positioned substantially in a predetermined spatial pattern. In one
embodiment, the predetermined spatial pattern is at least partially
periodic. In one embodiment, the plurality of frozen piercing
implements includes an area density of implements greater than or
approximately equal to 1 .mu.m, greater than or approximately equal
to 10 .mu.m, greater than or approximately equal to 50 .mu.m,
greater than or approximately equal to 100 .mu.m, greater than or
approximately equal to 500 .mu.m, greater than or approximately
equal to 1 mm, greater than or approximately equal to 10 mm,
greater than or approximately equal to 50 mm, greater than or
approximately equal to 100 mm, greater than or approximately equal
to 500 mm, greater than or approximately equal to 1 cm, or any
value there between. In one embodiment, the plurality of frozen
piercing implements include approximately the same length.
[0608] In one embodiment, the length of a frozen piercing implement
is associated with the position or location of the frozen piercing
implement in the array device. In one embodiment, the length of a
frozen piercing implement is actuatable. In one embodiment, at
least one frozen piercing implement is configured to be
deactivated. In one embodiment, the at least one frozen piercing
implement configured to be deactivated is deactivated by at least
one component of the array device or the frozen piercing implement.
In one embodiment, the at least one frozen piercing implement
configured to be deactivated is deactivated by thermal transfer to
the at least one frozen piercing implement.
[0609] In one embodiment, the plurality of frozen piercing
implements is positioned as at least a portion of a fluidic or
injection device. In one embodiment, the plurality of frozen
piercing implements is positioned in fluid communication with at
least one compartment configured to be mechanically regulated. In
one embodiment, at least one frozen piercing implement of the
plurality of frozen piercing implements includes one or more of
hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[0610] In one embodiment, at least one frozen piercing implement of
the plurality of frozen piercing implements is configured to
deliver at least one agent. In one embodiment, the at least one
major dimension includes at least one of the radius, diameter,
length, width, height, or perimeter. In one embodiment, at least
one frozen piercing implement of the plurality further comprises at
least one agent. In one embodiment, each frozen piercing implement
of the plurality includes at least one agent different than the
agent of every other frozen piercing implement of the plurality. In
one embodiment, at least one frozen piercing implement of the
plurality includes at least two different agents. In one
embodiment, the device includes at least two different agents. In
one embodiment, the at least one agent includes at least one
antigen. In one embodiment, each frozen piercing implement of the
plurality includes at least one antigen. In one embodiment, the at
least one antigen includes at least one allergen. In one
embodiment, the frozen piercing implement is configured for
delivering the at least one agent. In one embodiment, the at least
one agent includes at least one of a nontoxic, biocompatible,
bioresorbable, or biodegradable agent.
[0611] In one embodiment, at least two frozen piercing implements
of the plurality of frozen piercing implements have at least one
agent in common. In one embodiment, each frozen piercing implement
of the plurality of frozen piercing implements has at least one
agent in common. In one embodiment, each frozen piercing implement
of the plurality of frozen piercing implement is different from
every other piercing implement by varying one or more of: size of
implement, shape of implement, or constitution of implement. In one
embodiment, at least two frozen piercing implements of the
plurality of frozen piercing implement differ in one or more of:
size of implement, shape of implement, or constitution of
implement.
[0612] As described herein, in one embodiment, at least one of the
plurality of frozen peiercing implements is substantially solid at
approximately 0.degree. C., approximately -10.degree. C.,
approximately -20.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -75.degree. C., approximately -80.degree. C.,
approximately -85.degree. C., approximately -90.degree. C.,
approximately -95.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -180.degree. C., approximately -200.degree. C.,
approximately -220.degree. C., approximately -250.degree. C., or
any value less than or therebetween. Ranges for consideration of
substantially solid state are provided herein.
[0613] In one embodiment, the array device has at least one major
dimension of approximately one centimeter or less, approximately
one millimeter or less, approximately one micrometer or less,
approximately one nanometer, or any value therebetween. In one
embodiment, the plurality of frozen piercing implements includes a
two dimensional array. In one embodiment, the plurality of frozen
piercing implements includes a three dimensional array. In one
embodiment, the plurality of frozen piercing implements are
arranged in at least one configuration including a regular or
irregular shape. In one embodiment, the plurality of frozen
piercing implements are arranged in at least one configuration
including at least one of a rectangle, square, circle, triangle, or
polygon.
[0614] In one embodiment, at least one frozen piercing implement of
the plurality of frozen piercing implements includes at least one
functionalized surface. In one embodiment, the at least one
functionalized surface includes one or more functionalities
including one or more of charge functionality, hydrophobic
functionality, hydrophilic functionality, chemically reactive
functionality, organo functionality, or wetability. In one
embodiment, the at least one functionalized surface includes one or
more functional groups including at least one of an agent, alcohol,
hydroxyl, amine, aldehyde, dye, ketone, carbonyl, thiol,
alkoxysilane, phosphate, carboxyl, carboxylic acid, carboxylate,
nucleic acid, amino acid, polypeptide, protein, lipid,
carbohydrate, metal, --NH.sub.3.sup.+, --COOH, --COO--, --SO.sub.3,
CH.sub.2N.sup.+(CH.sub.3).sub.3, --(CH.sub.2).sub.xCH.sub.3,
--C((CH.sub.2).sub.xCF.sub.3).sub.3,
--CH.sub.2N(C.sub.2H.sub.5).sub.2, --NH.sub.2,
--(CH.sub.2).sub.xCOOH, --(OCH.sub.2CH.sub.2).sub.xCH.sub.3,
--SiOH, or --OH. In one embodiment, the at least one functionalized
surface includes at least part of an outer surface. In one
embodiment, the at least one functionalized surface includes at
least part of an inner surface.
[0615] In one embodiment, the array device further comprises at
least one channel. In one embodiment, the at least one channel
includes at least one cross-coupling flow channel. In one
embodiment, at least one frozen piercing implement of the plurality
of frozen piercing implements includes at least one inlet port. In
one embodiment, the at least one inlet port is in fluid
communication with at least one channel of at least one frozen
piercing implement. In one embodiment, the at least one inlet port
is in fluid communication with at least one channel of the array
device. In one embodiment, at least one frozen piercing implement
of the plurality of frozen piercing implements includes a plurality
of inlet ports. In one embodiment, at least one frozen piercing
implement of the plurality of frozen piercing implements includes
at least one outlet port. In one embodiment, the at least one
outlet port is in fluid communication with at least one channel of
at least one frozen piercing implement. In one embodiment, the at
least one outlet port is in fluid communication with at least one
channel of the array device. In one embodiment, at least one frozen
piercing implement of the plurality of frozen piercing implements
includes a plurality of outlet ports. In one embodiment, the array
device further comprises at least one of a nanoparticle,
microparticle, sensor, valve, gate, channel, transducer, actuator,
detector, heater, circuit, or detection material.
[0616] In one embodiment, at least one implement of the plurality
of frozen piercing implements includes at least one sensor. In one
embodiment, at least one implement of the plurality of frozen
piercing implements is configured for extracting at least one
material from at least one substrate. Various non-limiting examples
of materials capable of being sensed, extracted, or collected from
a substrate are provided herein.
[0617] In one embodiment, at least one implement of the plurality
of frozen piercing implements further includes at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, glycopeptide, glycolipid, lipoprotein, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus,
acid, support structure, buffer, protic solvent, aprotic solvent,
nitric oxide, nitrous oxide, nitric oxide synthase, amino acid,
micelle, polymer, copolymer, monomer, prepolymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
nanotube, piloxymer, transfersome, gas, element, contaminant,
radioactive particle, hormone, microorganism, bacteria, virus,
quantum dot, contrast agent, or any part thereof.
[0618] In one embodiment, the plurality of frozen piercing
implements includes at least approximately 2 implements,
approximately 5 implements, approximately 10 implements,
approximately 20 implements, approximately 50 implements,
approximately 100 implements, approximately 200 implements,
approximately 300 implements, approximately 400 implements,
approximately 500 implements, approximately 600 implements,
approximately 700 implements, approximately 800 implements,
approximately 900 implements, approximately 1000 implements,
approximately 5000 implements, approximately 10000 implements, or
any value therebetween or greater. In one embodiment, the spacing
between two or more frozen piercing implements includes at least
approximately 1 nm, approximately 5 nm, approximately 10 nm,
approximately 20 nm, approximately 50 nm, approximately 80 nm,
approximately 100 nm, approximately 200 nm, approximately 300 nm,
approximately 400 nm, approximately 500 nm, approximately 600 nm,
approximately 700 nm, approximately 800 nm, approximately 900 nm,
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 .mu.m, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 500 .mu.m, approximately 1 mm, approximately 5 mm,
approximately 10 mm, approximately 100 mm, approximately 500 mm,
approximately 1 cm, approximately 5 cm, approximately 10 cm, or any
value therebetween or greater. In one embodiment, the array device
further comprises at least one attachment component configured to
secure the array device to at least one substrate. In one
embodiment, the at least one attachment component includes at least
one adhesive material. In one embodiment, the device is configured
to substantially form a patch.
[0619] In one embodiment, the array device further comprises at
least one compartment.
[0620] In one embodiment, at least one compartment includes at
least one syringe or at least one valve. In one embodiment, at
least one compartment is configured to hold at least one material
extracted from at least one substrate. In one embodiment, at least
one agent includes at least one of an adhesive agent, therapeutic
agent, reinforcement agent, abrasive, biological remodeling agent,
or explosive material.
[0621] In one embodiment, the array device further comprises at
least one compartment in fluid communication with at least one
frozen piercing implement of the plurality of frozen piercing
implements. In one embodiment, the at least one compartment is
configured for holding at least one agent. In one embodiment, the
at least one compartment is configured for holding at least one
cryogenic substance. In one embodiment, the array device further
comprises a plurality of compartments in fluid communication with
at least one frozen piercing implement of the plurality of frozen
piercing implements. In one embodiment, the plurality of
compartments includes at least one first compartment configured to
hold at least one different substance from at least one second
compartment. In one embodiment, the plurality of compartments
includes at least one first compartment configured to hold at least
one first agent, wherein the at least one first agent is different
from at least one other agent located in at least one second
compartment. In one embodiment, the plurality of compartments
includes at least one first compartment configured to hold at least
one first agent, and at least one second compartment configured to
hold a pharmaceutically acceptable carrier or excipient. In one
embodiment, two or more compartments are configured to interact
with at least one means for intermixing the contents of the two or
more compartments prior to or during administration of the array
device to at least one substrate. In one embodiment, wherein the at
least one means for intermixing includes mechanical disruption of
at least one compartment, altering porosity of at least one
compartment, electrochemical degradation of at least one
compartment, valve opening of at least one compartment, chemical
degradation of at least one compartment, or altering magnetic field
of at least one compartment. In one embodiment, the array device is
in electronic communication with at least one computing device.
[0622] In one embodiment, a composition comprises a plurality of
frozen piercing implement array devices joined together.
[0623] In one embodiment, the at least one support structure for an
array device, fluidic device, or injection device includes at least
one of a nanoparticle, sensor, circuit, lens, heater, detector,
controller, or actuator. In one embodiment, the support structure
includes at least one wave guide.
[0624] In one embodiment, the heater includes a microheater or
nanoheater. In one embodiment, the detector includes a
microdetector or nanodetector. In one embodiment, the actuator
includes a microactuator or a nanoactuator. In one embodiment, the
actuator includes a rotational actuator including carbon nanotubes.
See, for example, Fennimore et al., Nature (Abstract) vol. 424, pp.
408-410 (2003), which is incorporated herein by reference. In one
embodiment, the actuator includes a biological molecular motor or
switch (e.g., kinesin, myosin, ATP synthase, etc.). See, for
example, Dessinges et al., PNAS vol. 101, no. 17, pp. 6439-6444
(2004); and the world wide web at: timeshighereducation
co.uk/story.asp?storyCode=202789§ioncode=26, the content
for each of which is incorporated herein by reference.
[0625] In one embodiment, the lens includes a liquid micro-lens
array activated by selective electrowetting on polar electric
crystals, including but not limited to litium niobate. See, for
example, Grilli et al., Optics Express, vol. 16, no. 11, (2008),
which is incorporated herein by reference.
[0626] In one embodiment, the frozen piercing implement, or frozen
piercing implement device, is configured to pierce at least one
substrate in a substantially painless manner. In one embodiment,
the frozen piercing implement, or frozen piercing implement device,
is configured to pierce one or more biological cells or tissues of
a subject in a substantially painless manner.
[0627] In one embodiment, the frozen piercing implement, or frozen
piercing implement device, is utilized in conjunction with at least
one other substrate-piercing tool, including but not limited to
transdermal agent delivery iontophoresis, ultrasound, vacuum,
viruses, pH, heat, light, chemical enhancers, electric fields,
photomechanical waves, mesotherapy, electroporation, electrofusion,
electroosmosis, velocity based enhancement techniques (such as
needle-free injections), tape stripping, powderjecting,
transfersomes, agent-embedded tattoos or other etchings, abrasion
or ablation, controlled heat aided delivery, laser radiation,
magnetophoresis, or others. See, for example, Kumar and Philip,
Trop. J. Pharm. Res. 6(1):633-644 (2007), which is incorporated
herein by reference. In one embodiment, the frozen piercing
implement or frozen particle composition includes at least one
general anesthetic. In one embodiment, the frozen piercing
implement or frozen particle composition including a general
anesthetic is configured to be used as at least part of a defense
weapon.
[0628] In one embodiment, the frozen piercing implement includes at
least one projection. In one embodiment, the frozen piercing
implement is configured to pierce at least one substrate to a depth
of approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 .mu.m, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, approximately 10 mm,
approximately 20 mm, approximately 30 mm, approximately 40 mm,
approximately 50 mm, approximately 60 mm, approximately 70 mm,
approximately 80 mm, approximately 90 mm, approximately 100 mm,
approximately 200 mm, approximately 300 mm, approximately 400 mm,
approximately 500 mm, approximately 600 mm, approximately 700 mm,
approximately 800 mm, approximately 900 mm, approximately 1 cm,
approximately 10 cm, approximately 20 cm, or any value
therebetween.
[0629] In one embodiment, the frozen particle implement
administration depth is controlled by mechanical means. For
example, the implement administration depth may be limited by a
sheath or casing. In one embodiment, the frozen particle implement
depth is controlled by a positioner on the array that can control
the depth of administration. In one embodiment, the positioner is
configured to mechanically control the depth of administration of
at least one frozen piercing implement (or other implement if
located in an array device). Other factors that can influence
administration depth include the geometry of the implement,
constitution of the implement, administration time, manner of
administration, or at least one parameter of the substrate
(including, but not limited to temperature, constitution, density,
location, etc.)
[0630] In one embodiment, one or more frozen piercing implement
array device includes at least two frozen piercing implements
positioned on or through the surface of at least one base or
support structure. In one embodiment, a flange or other member is
configured on the array device to provide physical support to the
device, to provide stabilization when the device is placed on the
substrate, or to control penetration of the substrate by the at
least one piercing implement.
[0631] In one embodiment, the frozen piercing implement array
device is an in-plane array device. In one embodiment, the frozen
piercing implement array device is an out-of-plane array
device.
[0632] In one embodiment, the device includes a particular
arrangement of the piercing implements on the base or support
structure (e.g., square, hexagonal, triangular, diamond,
rectangular, or other patterning), varying the distribution of the
piercing implements within a specific patterned or designed array
device, varying at least one dimension of the piercing implement
(e.g., number of piercing implements, piercing implement radius,
etc.), number of solid versus channeled piercing implements, among
other features, can affect the functionality of the array device.
See, for example, Al-Qallaf and Bhusan Das, J Drug Target., vol.
17, no. 2, pp. 108-122 (2009), which is incorporated herein by
reference.
[0633] Furthermore, optimization of the surface area of the array
device, optimization of the piercing implement radius and length,
optimization of the number of piercing implements per row,
optimization of the aspect ratio of the distance between piercing
implements, while considering the substrate thickness or
permeability, can be conducted according to well-established
principles. Id. For example, the following equation has been used
in published studies to calculate skin permeability when using
microneedles: K=f (D/Lh), where K is the approximate skin
permeability of the agent (or other agent) intended to be
administered, f is the approximate fractional skin area after
insertion by the microneedles, D is the approximate effective
diffusion coefficient of the therapeutic agent in the skin, and
L.sub.h is the approximate length of the hole resulting from the
piercing of the skin. Id. In one embodiment, the therapeutic agent
molecules may traverse through various disruptions in the skin
thickness (i.e., epidermis) from the frozen piercing implement of
the array device to the blood supply. In one embodiment, the agent
may be absorbed as the frozen piercing implement melts or
sublimates. In one embodiment, particularly with channeled, or
hollowed, microneedles, the therapeutic agent may move through the
bore of the implement. In one embodiment, the path of the
therapeutic agent represents the approximate length of the
microneedle. In one embodiment, the path of the therapeutic agent
may be less than or greater than the approximate length of the
microneedle due to expansion or contraction of the microneedle upon
contact or penetration of the substrate.
[0634] In one embodiment, the array device is administered to at
least one external surface of a subject. In one embodiment, the
array device is administered to at least one internal surface of a
subject (for example, by utilizing a catheter, laparascope, or
other tool). In one embodiment, the array device is surgically
implanted into a subject.
[0635] In one embodiment, the one or more frozen piercing
implements are combined with at least one syringe. In one
embodiment, the syringe includes a micro- or nano-syringe. In one
embodiment, the one or more frozen piercing implements are combined
with at least one pen-type delivery device. For example, the
pen-type delivery device includes a housing assembly, a hub
assembly, a plunger for driving the piercing implement out of the
housing assembly and into the substrate, an optional compartment
containing a desired substance to be administered, and an optional
mechanism for piercing the compartment and releasing the substance.
See, for example, U.S. Patent App. Pub. No. 20030050602, which is
incorporated herein by reference.
[0636] In one embodiment, one or more frozen piercing implements
are combined with a fluidic system. In one embodiment, the fluidic
system includes a microfluidic system. In one embodiment, the
fluidic system includes a nanofluidic system. In one embodiment,
the fluidic system includes at least one of a a channel, pump,
sensor, injector, actuator, heater, detector, controller,
transducer, receiver, transmitter, circuit, lens, tunable lens,
valve, gate, nanoparticle, microparticle, power source, or
detection material.
[0637] In one embodiment, the valve includes a valve actuated by a
motor. In one embodiment, the valve includes a slide-valve,
optionally actuated by a motor. As described herein, in one
embodiment, the motor includes a biological based motor (e.g.
kinesin, myosin, ATP synthase), or a micro- or nano-stepping motor.
See, for example, Morishima et al, 7.sup.th Int. Conf. Miniaturized
Chem. and Biochem. Anal. Sys. pp. 1033-1036 (Oct. 5-9, 2003), which
is incorporated herein by reference.
[0638] In one embodiment, the fluidic device includes a closed loop
system capable of delivering at least one agent, sensing, or
extracting at least one material from at least one substrate. In
one embodiment, the fluidic system includes at least one
compartment. In one embodiment, the fluidic system senses or
analyzes at least one material from at least one substrate. In one
embodiment, the analysis includes sensing an enzyme or enzymatic
reaction including, but not limited to glucose oxidase or glucose
dehydrogenase. In one embodiment, the fluidic device includes at
least one transducer, such as an electrochemical or optical
transducer.
[0639] In one embodiment, the fluidic system includes detecting or
sensing at least one material from the at least one substrate,
extracting the at least one material in order to analyze and
determine a medical treatment (including preventative, diagnostic,
or responsive), and administering at least one agent. In one
embodiment, the closed loop system is configured in the form of a
patch, bandage, or other attachment vehicle.
[0640] In one embodiment, a sensor, such as an enzyme electrode for
glucose, for example, includes a screen-printed electrode on the
surface of which is immobilized glucose oxidase, and an electron
mediator, such as ferrocene or its derivatives. Electrons generated
by the oxidation of glucose are transferred from glucose oxidase to
the electrode by way of the mediator, and the concentration of
glucose is proportional to the current generated. See, for example,
U.S. Pat. No. 7,344,499, which is incorporated herein by reference.
In one embodiment, near-infrared spectroscopy is utilized for
detecting at least one material in at least one substrate. For
example, the concentration of extracted glucose in a gel is
detected by the absorption of the near-infrared light that passes
through the chamber. Id.
[0641] In one embodiment, at least one frozen piercing implement is
adapted to include at least one sensor or sensing component. For
example, an enzyme (such as glucose oxidase) can be coated on the
surface of one or more frozen piercing implements, distributed
within the frozen piercing implement, or at least partially filling
an otherwise hollow frozen piercing implement.
[0642] In one embodiment, the frozen piercing implement device
includes at least one sensor in communication with at least one
electronic component. In one embodiment, the at least one
electronic component includes at least one of a power source (for
example, a battery), transducer, storage device, display, receiver,
or other electronic component. The at least one electronic
component can be included with at least one piercing implement,
support structure, compartment, or other aspect of the frozen
piercing implement device.
[0643] In one embodiment, the at least one sensor can be calibrated
by utilizing the concentration of at least one same or different
analyte, measured by another means. For example, the analyte can be
normalized (by a linear or non-linear relationship), reducing the
variability between analysis events.
[0644] In one embodiment, the fluidic device includes at least one
attachment component configured to secure the array device to at
least one substrate. In one embodiment, the at least one attachment
component includes at least one adhesive material.
[0645] In one embodiment, the fluidic device includes at least one
vacuum to induce flow in at least one direction through at least
one piercing implement.
[0646] In one embodiment, the frozen piercing implement includes at
least one surfactant. In one embodiment, the surfactant includes at
least one ionic surfactant. In one embodiment, the at least one
ionic surfactant includes one or more of an alkyl ammonium salt,
bile acid or salt, fatty acid, carnitine, oligopeptide,
polypeptide, acyl lactylate, mono-diacetylated tartaric acid ester
of a mono-diglyceride, succinylated monoglyceride, citric acid
ester of mono-diglyceride, alginate salt, propylene glycol
alginate, lecithin, hydrogenated lecithin, lysolecithin,
hydrogenated lysolecithin, lysophospholipid, phospholipid,
alkylsulfate salt, fatty acid salt, sodium docusate, or mixtures or
derivatives of any thereof.
Additional Methods, Devices, and Systems for Making and
Administering Frozen Particle Compositions, Frozen Piercing
Implements, and Frozen Piercing Implement Devices
[0647] As described herein, a device or machine (including a
computer) may be utilized in various aspects relating to
compositions, methods, or systems relating to one or more frozen
particle compositions, or frozen piercing implements. Non-limiting
examples of such aspects may include predicting or calculating
various properties or characteristics relating to the one or more
frozen particle compositions, or frozen piercing implements, any
substrate, any subject, any administration device, or any
administration protocol. Any method disclosed herein is implicitly
intended to also include "means for" carrying out the method. One
or more methods disclosed include computer-implemented methods.
[0648] In one embodiment, a method or means for making one or more
frozen particle compositions, or frozen piercing implements
optionally includes at least one agent. In one embodiment, a method
or means for administering or delivering one or more frozen
particle compositions, or frozen piercing implements is disclosed.
In one embodiment, a method or means for administering at least one
frozen particle composition, or frozen piercing implement includes
administering at least one agent to a substrate.
[0649] In one embodiment, at least one computer system is
configured to provide one or more instructions to one or more
devices for deposition or administration of one or more frozen
particle compositions, or frozen piercing implements. In one
embodiment, at least one device is configured to deposit or
administer one or more frozen particle compositions, or frozen
piercing implements on any x, y, or z axis. In one embodiment, the
at least one computer system provides one or more instructions for
predicting, controlling, or varying the administration of one or
more frozen particle compositions, or frozen piercing implements or
deposition of at least one agent included in the one or more frozen
particle compositions, or frozen piercing implements on any x, y,
or z location. In one embodiment, the at least one computer system
provides one or more instructions for temporal, spatial, or
regional locations for deposition or administration of one or more
frozen particle compositions, or frozen piercing implements. Other
components of the at least one computer system or device are
included in the figures as described.
[0650] In one embodiment, one or more methods, devices, or systems
described herein include making or administering one or more frozen
particle compositions or frozen piercing implements. In one
embodiment, frozen particle compositions or frozen piercing
implements as described herein are made by one or more processes.
In one embodiment, at least one process described herein is
adaptable for a micro- or nano-scale fabrication of the frozen
particle compositions, or frozen piercing implements. See, for
example, U.S. Patent Application Publication No. 20020193754, which
is incorporated herein by reference.
[0651] In one embodiment, a method for making at least one frozen
piercing implement includes etching a frozen composition with a
chemical. In one embodiment, the chemical includes at least one
alcohol. In one embodiment, the alcohol includes at least one of
methanol, or ethanol. In one embodiment, the chemical agent
includes at least one salt or salt solution. In one embodiment, a
method for making at least one frozen piercing implement includes
etching a frozen composition with an acid or a base. In one
embodiment, a method for making at least one frozen piercing
implement includes etching a frozen composition with oxyfuel gas
cutting (sometimes referred to as "flame cutting"). In one
embodiment, the base includes sodium hydroxide, chromium trioxide,
ammonium fluoride, ammonium hydroxide, hydrogen peroxide, or
potassium hydroxide.
[0652] In one embodiment, the acid includes phenol, acetic acid,
nitric acid, hydrofluoric acid, sulfuric acid, phosphoric acid, or
hydrochloric acid. In one embodiment, a method for making at least
one piercing implement includes etching a frozen composition with
fluid hydrogen oxide (e.g., gas or liquid). In one embodiment, a
method for making at least one piercing implement includes etching
a frozen composition with a fluid form of at least one constituent
of the frozen composition (including but not limited to a frozen
block or film).
[0653] In one embodiment, the etching includes a fluid jet stream.
For example, in one embodiment, a water jet cutter is utilized in
etching at least one frozen composition. In one embodiment, the
fluid jet stream includes a gas or liquid jet stream. In one
embodiment, the fluid jet stream includes at least one chemical. In
one embodiment, the at least one chemical includes at least one
agent. In one embodiment, the at least one chemical includes at
least one polymer (e.g., a linear macromolecular partially
hydrolyzed polyacrylamide, such as found in SUPER WATER , available
from Berkeley Chemical Research, Inc.)
[0654] In one embodiment, the fluid jet stream includes air. In one
embodiment, the pressure of the fluid jet stream includes at least
approximately 0.5 psi, approximately 1 psi, approximately 5 psi,
approximately 10 psi, approximately 20 psi, approximately 30 psi,
approximately 40 psi, approximately 50 psi, approximately 60 psi,
approximately 70 psi, approximately 80 psi, approximately 90 psi,
approximately 100 psi, approximately 150 psi, approximately 200
psi, approximately 500 psi, approximately 1,000 psi, approximately
5,000 psi, approximately 10,000 psi, approximately 20,000 psi,
approximately 30,000 psi, approximately 40,000 psi, approximately
50,000 psi, approximately 60,000 psi, approximately 70,000 psi,
approximately 80,000 psi, approximately 90,000 psi, or any value
therebetween or greater. The pressure of the fluid jet stream can
also be adjusted according to other factors, including but not
limited to the width or diameter of the stream, the abrasive flow
rate, or the jet stream traverse rate. See, for example, Srinivasu
and Babu, Appl. Soft Comp. vol. 8, pp. 809-819 (2008), which is
incorporated herein by reference. For example, a narrow jet stream
will generally have greater cutting power than a wider jet stream
due to increased pressure at the nozzle. See, for example, the
world wide web at jetedge.com, the content of which is incorporated
herein by reference.
[0655] In one embodiment, the etching includes thermal etching. For
example, crystalline substances can be etched in a saturated air
atmosphere, with an etching time of a few seconds, to several
weeks. See, for example, Krausz and Gold, J of Colloid and
Interface Sci., vol. 25, pp. 255-262 (1967).
[0656] In one embodiment, the etching includes laser etching. For
example, frozen piercing implements can be cut from a film, sheet,
strip, block, or other form of frozen composition with an infrared
laser. In one embodiment, the laser is guided by a CAD/CAM
design.
[0657] In one embodiment, bores are etched (for example, with a
physical or chemical etchant) in the material (such as a frozen
composition) and the remainder of the piercing implement is etched
away around the bores. In one embodiment, the piercing implements
and their bores (if included) are etched simultaneously, or bores
are etched into existing piercing implements.
[0658] In one embodiment, bores from the backside of the material
(such as a frozen composition) are generated using a
front-to-backside infrared alignment, and etching from the backside
of the material.
[0659] In one embodiment, the etching time includes at least
approximately 10 seconds, at least approximately 20 seconds, at
least approximately 30 seconds, at least approximately 1 minute, at
least approximately 5 minutes, at least approximately 10 minutes,
at least approximately 20 minutes, at least approximately 30
minutes, at least approximately 2 hours, at least approximately 5
hours, at least approximately 10 hours, at least approximately 24
hours, at least approximately 2 days, at least approximately 5
days, at least approximately 1 week, at least approximately 2
weeks, at least approximately 3 weeks, at least approximately 1
month, at least approximately 3 months, or any value therebetween.
Various factors can influence the etching time required, including
but not limited to at least one of: etching temperature, etching
chemical, constitution of material being etched, thickness of
material being etched, or desired characteristic of the frozen
piercing implement(s).
[0660] The etched radius for a particular composition can be
controlled by varying the etchant (e.g., chemical, thermal, or
other), the amount of time exposed to the etchant, the temperature
of the etchant or etching environment, the constituency of the
composition being etched, desired size, or shape of the etching,
thickness of the composition being etched, or other factors.
[0661] In one embodiment, the frozen particle compositions, or
frozen piercing implements, are designed with the aid of a computer
device, computer system, computer program product, or
computer-implemented method. In one embodiment, the frozen particle
compositions, or frozen piercing implements, are generated with the
aid of a computer device, computer system, computer program
product, or computer-implemented method. In one embodiment, the
frozen particle compositions, or frozen piercing implements, are
administered with the aid of a computer device, computer system,
computer program product, or computer-implemented method.
[0662] In one embodiment, a simulation for a mask is generated,
optionally with assistance from a computer device, computer system,
computer program product, or computer-implemented method. See, for
example, Wilke et al., Euro. Micro & Nano Systems 20-21 (2004),
which is incorporated herein by reference. As discussed by Wilke et
al., a mask can be designed on the basis of a Simode simulation,
and optical microscopy as well as scanning electron microscopy can
be utilized to examine single microneedles resulting from the
etching process. Id. Thus, by varying the etching times,
temperatures, and other factors, microneedles can be consistently
reproduced with high accuracy. Id. In one embodiment, an array
device including a plurality of microneedles can be generated that
can be peeled off for use. Id.
[0663] In one embodiment, a thermal etchant is utilized for
fabricating one or more frozen piercing implements. In one
embodiment, a fluid jet (e.g., gas or liquid) is utilized for
etching one or more frozen piercing implements. In one embodiment,
a laser beam is utilized for etching one or more frozen piercing
implements. In one embodiment, an electron beam is utilized for
etching one or more frozen piercing implements. In one embodiment,
an ion beam is utilized for etching one or more frozen piercing
implements.
[0664] In one embodiment, at least one frozen fluid (including but
not limited to at least one solid condensed gas) is deposited onto
a cryogenically cooled support surface (e.g., metal, or silicon
surface) in the chamber of a combined scanning electron microscope
and focused ion beam apparatus (FEI Co., Hillsboro, Oreg.). See,
for example, King et al, Nano Lett. vol. 5, pp. 1157-1160 (2005),
which is herein incorporated by reference. Next, the ice surface is
exposed to focused energetic electron or gallium ion beams, which
stimulates local removal of ice. Id. In one embodiment, the beams
are programmed to produce at least one pattern in the ice. Id.
Additional ice can be removed by in situ sublimation (e.g., by
eliminating liquid surface tension effects) by fluid jet, or by
other means. Id.
[0665] In one embodiment, the ice is deposited at a rate of
approximately 1 pm/second, approximately 1 nm/second, approximately
1 mm/second, approximately 1 cm/second, or any value therebetween.
In one embodiment, the ice is deposited using a leak valve
controlled vapor flow that is directed onto the cooled support
surface or sample. In one embodiment, the cooled sample or cooled
support surface is maintained at approximately 128 K (approximately
-145.degree. C.). Id. In one embodiment, the fluid includes
hydrogen oxide. In one embodiment, the hydrogen oxide is deposited
on the cooled support surface by way of a magnesium sulfate-water
vapor source, and water vapor pressure is controlled by at least
one leak valve. Id.
[0666] In one embodiment, the etching system includes at least one
cold finger located near the sample surface to ensure a sufficient
thermal gradient to keep unwanted species from condensing on the
support surface or sample surface. Id. In one embodiment, the cold
finger is placed approximately 1 mm from the surface, approximately
2 mm from the surface, approximately 3 mm from the surface,
approximately 4 mm from the surface, approximately 5 mm from the
surface, approximately 6 mm from the surface, approximately 7 mm
from the surface, approximately 8 mm from the surface,
approximately 9 mm from the surface, approximately 10 mm from the
surface, approximately 1 cm from the surface, approximately 1 dm
from the surface, or any value therebetween. In one embodiment, the
temperature of the sample surface can be controlled within
approximately +/-1 K (approximately +/-1 degree C.). Id. In one
embodiment, scanning electron microscopy can be utilized to observe
etching of the frozen fluid composition. Id.
[0667] In one embodiment, the laser beam includes at least one of a
carbon dioxide laser, or a Erbium:YAG laser. See, for example, U.S.
Patent Application Publication No. 20080290065, which is herein
incorporated by reference. Erbium:YAG lasers are commonly used in
the medical sector, since the laser beam pinpoints the maxium
absorption spike of water. Id. In one embodiment, the laser beam
(e.g., carbon dioxide, erbium:YAG, eximer, argon, KTP, krypton
fluoride, xenon chloride, xenon fluoride, helium neon,
neodynmium:YAG, erbium glass, erbium: YAG, holmium:YAG, Ruby
(chromium sapphire), gallium arsenide, or other) etches a frozen
fluid by way of explosive vaporization. Id.
[0668] In one embodiment, the laser type is selected based on the
absorption wavelength of laser energy by the frozen composition.
Such an absorption profile can be generated, if not already known,
using standard techniques.
[0669] In one embodiment, the laser beam is part of an etching
system for forming one or more frozen piercing implements. In one
embodiment, the laser system includes at least one first mirror
that is optionally connected to at least one first driver under
command of at least one controller. In one embodiment, the laser
system includes at least one second mirror that is optionally
connected to at least one second driver under command of at least
one controller. In one embodiment, the at least one first driver
and the at least one second driver are the same driver. In one
embodiment, the at least one first driver and the at least one
second driver are different drivers. In one embodiment, at least
one of the at least one first driver or the at least one second
driver includes at least one of a servo-galvanometer driver device,
or a stepper motor driver device. Id.
[0670] In one embodiment, the at least one first mirror controls
x-axis positioning of the laser. In one embodiment, the at least
one second mirror controls y-axis positioning of the laser. In one
embodiment, the etching system includes at least one third mirror.
In one embodiment, the at least one third mirror is configured to
operate as a shutter for directing the laser beam away from the
material to be etched. In one embodiment, the laser system includes
one or more instructions for etching the frozen material into one
or more frozen piercing implements.
[0671] In one embodiment, the frozen particle compositions, or
frozen piercing implements, are fabricated by pouring a liquid
suspension, solution, or mixture, of the desired constituents into
a vessel, mold or frame, and optionally completing the filling
under vacuum. See, for example, Park et al., Pharm Res. vol. 23,
no. 5 (2006), which is incorporated herein by reference. Following
filling the mold, the constituents of the mold are optionally
concentrated by way of evaporation or other process. Id. Next, the
mold is frozen under conditions and time sufficient to at least
partially solidify the constituents of the mold. Finally, the
frozen particle compositions, or frozen piercing implements, are
released from the vessel, mold or frame. Id.
[0672] As discussed herein, the conditions and time sufficient to
at least partially solidify at least one fluid includes the
particular points of state function or phase transition for the
fluid. For example, first-order phase transitions involve a latent
heat. During a first-order phase transition, the system either
absorbs or releases a fixed amount of energy, and the temperature
of the system stays constant as heat is added. In another example,
second-order phase transitions have no associated latent heat, such
as the glass transition of polymeric materials at the glass
transition temperature of the polymer. The glass transition
temperature can be measured by the change in the slope of the
heating energy versus temperature curve that results from the
measurement on a differential scanning calorimetry device.
Accordingly, a fluid composition's phase or state varies with
certain parameters of the conditions sufficient to at least
partially solidify the fluid composition. For example, the state
variables of pressure and temperature assist to define specific
conditions sufficient to at least partially solidify a particular
fluid.
[0673] As discussed herein, the mold or frame can be made from any
material that allows fabrication of the frozen piercing implements.
In one embodiment, the mold or frame itself is frozen. In one
embodiment, the mold or frame includes at least one metal, glass,
or plastic. In one embodiment, the mold or frame is disposable. In
one embodiment, the mold or frame is reusable.
[0674] In one embodiment, the frozen particle compositions, or
frozen piercing implements are spray or dip coated with at least
one agent. Id. In one embodiment, the at least one agent includes
at least one adhesive agent, therapeutic agent, reinforcement
agent, biological remodeling agent, abrasive, or explosive
material.
[0675] In one embodiment, the frozen particle compositions, or
frozen piercing implements, are fabricated by layer deposition on a
support structure (which may or may not be frozen).
[0676] In one embodiment, the frozen particle compositions, or
frozen piercing implements, are fabricated by drawing lithography.
See, for example, WO2008010682, which is incorporated herein by
reference. In one embodiment, the frozen particle compositions, or
frozen piercing implements, are fabricated as solid or hollow
compositions by laying down a frozen composition on the surface of
a support structure, and removing the implement.
[0677] In one embodiment, one or more frozen particle compositions
or frozen piercing implements are made by spraying at least one
fluid composition into at least one compartment. In one embodiment,
the at least one compartment includes at least one fluid. In one
embodiment, the at least one fluid includes at least one gas or
liquid. In one embodiment, the at least one fluid includes at least
one supercooled liquid. In one embodiment, the at least one liquid
includes liquid nitrogen, liquid carbon dioxide, liquid argon,
liquid helium, or other inert or reactive liquid. In one
embodiment, the at least one fluid includes at least one of liquid
nitrogen, liquid carbon dioxide, liquid hydrogen, liquid oxygen,
liquid helium, liquid methane, methane/ammonia, a halogenated
hydrocarbon, liquid neon, liquid argon, liquid mercury, air, cold
saline, cold sodium hydroxide, cold potassium hydroxide, cold
potassium chloride, cold sodium chloride solution, or hydrogen
sulfide. In one embodiment, the at least one fluid includes at
least one of tetrachloromethane; trichlorofluoromethane;
dichlorodifluoromethane; bromochlorodifluoromethane;
dibromodifluoromethane; chlorotrifluoromethane;
bromotrifluoromethane; carbon tetrafluoride; trichloromethane;
dichlorofluoromethane; chlorodifluoromethane; bromodifluoromethane;
drifluoromethane; dichloromethane; chloromethane; fluoromethane;
methane; hexachloroethane; pentachlorofluoroethane;
1,1,2,2,-tetrachloro-1,2-difluoroethane;
1,1,1,2-tetrachloro-2,2-difluoroethane;
1,1,2-trichlorotrifluoroethane; 1,1,1-trichlorotrifluoroethane;
1,2-dichlorotetrafluoroethane; 1,1-dichlorotetrafluoroethane;
dibromoetetrafluoroethane; chloropentafluoroethane;
hexafluoroethane; pentachloroethane;
1,1,2,2-tetrachloro-1-fluoroethane;
1,1,2-trichloro-2,2-difluoroethane;
1,1,2-trichloro-1,2-difluoroethane;
1,1,1-trichloro-2,2-difluoroethane;
2,2-dichloro-1,1,1-trifluoroethane;
1,2-dichloro-1,1,2-trifluoroethane;
1,1-dichloro-1,2,2-trifluoroethane;
2-chloro-1,1,2,2-tetrafluoroethane; pentafluoroethane;
(difluoromethoxy)(trifluoro)methane; 1,1,2,2-tetrachloroethane;
1,1,1,2-tetrachloroethane; 1,1,2-trichloro-2-fluoroethane;
1,1,2-trichloro-1-fluoroethane; 1,1,1-trichloro-2-fluoroethane;
dichlorodifluoroethane; 1,1,-dichloro-2,2-difluoroethane;
1,2-dichloro-1,1-difluoroethane; 1,1-dichloro-1,2-difluoroethane;
1,2-dibromo-1,1-difluoroethane; 1-chloro-1,2,2-trifluoroethane;
1-chloro-2,2,2-trifluoroethane; 1-chloro-1,1,2-trifluoroethane;
1,1,2,2-tetrafluoroethane; 1,1,1,2-tetrafluoroethane,
bis(difluoromethyl)ether; 1,1,2-trichloroethane;
1,1,1-trichloroethane; 1,2-dichloro-1-fluoroethane;
1,2-dibromo-1-fluoroethane; 1,1-dichloro-1-fluoroethane;
chlorodifluoroethane; 1-chloro-1,2-difluoroethane;
1-chloro-1,1-difluoroethane; 1,1,2-trifluoroethane;
1,1,1-trifluoroethane; methyl trifluoromethyl ether;
2,2,2-trifluoroethyl methyl ether; 1,2-dichloroethane;
1,1-dichloroethane; chlorofluoroethane; 1-chloro-1-fluoroethane;
1,2-difluoroethane; 1,1-difluoroethane; chloroethane; fluoroethane;
ethane; 1,1,1,2,2,3,3-heptachloro-3-fluoropropane;
hexachlorodifluoropropane;
1,1,1,3,3-pentachloro-2,2,3-trifluoropropane;
1,2,2,3-tetrachloro-1,1,3,3-tetrafluoropropane,
1,1,1-trichloro-2,2,3,3,3-pentafluoropropane;
1,2-dichloro-1,1,2,3,3,3-hexafluoropropane;
1,3-dichloro-1,1,2,2,3,3-hexafluoropropane;
1-chloro-1,1,2,2,3,3,3-heptafluoropropane;
2-chloro-1,1,1,2,3,3,3-heptafluoropropane; octafluoropropane;
1,1,1,2,2,3-hexachloro-3-fluoropropane; pentachlorodifluoropropane;
1,1,1,3,3-pentachloro-2,2-difluoropropane,
tetrachlorotrifluoropropane;
1,1,3,3-tetrachloro-1,2,2-trifluoropropane;
1,1,1,3-tetrachloro-2,2,3-trifluoropropane;
trichlorotetrafluoropropane;
1,3,3-trichloro-1,1,2,2-tetrafluoropropane;
1,1,3-trichloro-1,2,2,3-tetrafluoropropane;
1,1,1-trichloro-2,2,3,3-tetrafluoropropane;
dichloropentafluoropropane;
2,2-dichloro-1,1,1,3,3-pentafluoropropane;
2,3-dichloro-1,1,1,2,3-pentafluoropropane;
1,2-dichloro-1,1,2,3,3-pentafluoropropane;
3,3-dichloro-1,1,1,2,2-pentafluoropropane;
1,3-dichloro-1,1,2,2,3-pentafluoropropane;
1,1-dichloro-1,2,2,3,3-pentafluoropropane;
1,2-dichloro-1,1,3,3,3-pentafluoropropane;
1,3-dichloro-1,1,2,3,3-pentafluoropropane;
1,1-dichloro-1,2,3,3,3-pentafluoropropane; chlorohexafluoropropane;
2-chloro-1,1,1,2,3,3-hexafluoropropane;
3-chloro-1,1,1,2,2,3-hexafluoropropane;
1-chloro-1,1,2,2,3,3-hexafluoropropane;
2-chloro-1,1,1,3,3,3-hexafluoropropane;
1-chloro-1,1,2,3,3,3-hexafluoropropane;
1,1,2,2,3,3,3-heptafluoropropane; trifluoromethyl
1,1,2,2-tetrafluoroethyl ether; 1,1,1,2,3,3,3-heptafluoropropane;
trifluoromethyl 1,2,2,2-tetrafluoroethyl ether;
pentachlorofluoropropane; tetrachlorodifluoropropane;
1,1,3,3-tetrachloro-2,2-difluoropropane;
1,1,1,3-tetrachloro-2,2-difluoropropane; trichlorotrifluoropropane;
1,1,3-trichloro-2,2,3-trifluoropropane;
1,1,3-trichloro-1,2,2-trifluoropropane;
1,1,1-trichloro-2,2,3-trifluoropropane; dichlorotetrafluoropropane;
2,2-dichloro-1,1,3,3-tetrafluoropropane;
2,2-dichloro-1,1,1,3-tetrafluoropropane;
1,2-dichloro-1,2,3,3-tetrafluoropropane;
2,3-dichloro-1,1,1,2-tetrafluoropropane;
1,2-dichloro-1,1,2,3-tetrafluoropropane;
1,3-dichloro-1,2,2,3-tetrafluoropropane;
1,1-dichloro-2,2,3,3-tetrafluoropropane;
1,3-dichloro-1,1,2,2-tetrafluoropropane;
1,1-dichloro-1,2,2,3-tetrafluoropropane;
2,3-dichloro-1,1,1,3-tetrafluoropropane;
1,3-dichloro-1,1,3,3-tetrafluoropropane;
1,1-dichloro-1,3,3,3-tetrafluoropropane; chloropentafluoropropane;
1-chloro-1,2,2,3,3-pentafluoropropane;
3-chloro-1,1,1,2,3-pentafluoropropane;
1-chloro-1,1,2,2,3-pentafluoropropane;
2-chloro-1,1,1,3,3-pentafluoropropane;
1-chloro-1,1,3,3,3-pentafluoropropane;
1,1,1,2,2,3-hexafluoropropane; 1,1,1,2,3,3-hexafluoropropane;
1,1,1,3,3,3-hexafluoropropane; 1,2,2,2-tetrafluoroethyl
difluoromethyl ether; hexafluoropropane; tetrachlorofluoropropane;
trichlorodifluoropropane; dichlorotrifluoropropane;
1,3-dichloro-1,2,2-trifluoropropane;
1,1-dichloro-2,2,3-trifluoropropane;
1,1-dichloro-1,2,2-trifluoropropane;
2,3-dichloro-1,1,1-trifluoropropane;
1,3-dichloro-1,2,3-trifluoropropane;
1,3-dichloro-1,1,2-trifluoropropane; chlorotetrafluoropropane;
2-chloro-1,2,3,3-tetrafluoropropane;
2-chloro-1,1,1,2-tetrafluoropropane;
3-chloro-1,1,2,2-tetrafluoropropane;
1-chloro-1,2,2,3-tetrafluoropropane;
1-chloro-1,1,2,2-tetrafluoropropane;
2-chloro-1,1,3,3-tetrafluoropropane;
2-chloro-1,1,1,3-tetrafluoropropane;
3-chloro-1,1,2,3-tetrafluoropropane;
1-chloro-1,1,1,2-tetrafluoropropane;
1-chloro-1,1,2,3-tetrafluoropropane;
3-chloro-1,1,1,3-tetrafluoropropane;
1-chloro-1,1,3,3-tetrafluoropropane; 1,1,2,2,3-pentafluoropropane;
pentafluoropropane; 1,1,2,3,3-pentafluoropropane;
1,1,1,2,3-pentafluoropropane; 1,1,1,3,3-pentafluoropropane; methyl
pentafluoroethyl ether; difluoromethyl 2,2,2-trifluoroethyl ether;
difluoromethyl 1,1,2-trifluoroethyl ether; trichlorofluoropropane;
dichlorodifluoropropane; 1,3-dichloro-2,2-difluoropropane;
1,1-dichloro-2,2-difluoropropane; 1,2-dichloro-1,1-difluoropropane;
1,1-dichloro-1,2-difluoropropane; chlorotrifluoropropane
2-chloro-1,2,3-trifluoropropane; 2-chloro-1,1,2-trifluoropropane;
1-chloro-2,2,3-trifluoropropane; 1-chloro-1,2,2-trifluoropropane;
3-chloro-1,1,2-trifluoropropane; 1-chloro-1,2,3-trifluoropropane;
1-chloro-1,1,2-trifluoropropane; 3-chloro-1,3,3-trifluoropropane;
3-chloro-1,1,1-trifluoropropane; 1-chloro-1,1,3-trifluoropropane;
1,1,2,2-tetrafluoropropane; methyl 1,1,2,2-tetrafluoroethyl ether;
dichlorofluoropropane; 1,2-dichloro-2-fluoropropane;
chlorodifluoropropane; 1-chloro-2,2-difluoropropane;
3-chloro-1,1-difluoropropane; 1-chloro-1,3-difluoropropane;
trifluoropropane; chlorofluoropropane; 2-chloro-2-fluoropropane;
2-chloro-1-fluoropropane; 1-chloro-1-fluoropropane;
difluoropropane; fluoropropane; propane;
dichlorohexafluorocyclobutane; chloroheptafluorocyclobutane;
octafluorocyclobutane; decafluorobutane; perfluoropropyl methyl
ether; perfluoroisopropyl methyl ether;
1,1,1,3,3-pentafluorobutane; tetradecafluorohexane; butane;
isobutane; pentane; isopentane; diethyl ether; methyl formate;
methylamine; ethylamine; nitrous oxide; sulfur dioxide; krypton;
1,1-dichloro-2,2-difluoroethylene; chlorotrifluoroethylene;
tetrafluoroethylene; trichloroethylene; cis-1,2-dichloroethylene;
1,1-difluoroethylene; chloroethylene; fluoroethylene; ethylene;
hexafluoropropylene; hexafluoropropene trimer; propylene;
hydrofluorocarbon; chlorofluorocarbon; hydrochlorofluorocarbon; or
the like.
[0678] In one embodiment, the at least one fluid composition is
sprayed beneath the surface of the fluid bath. In one embodiment,
the at least one fluid composition is sprayed just above the
surface of the fluid bath. In one embodiment, at least one
mechanism is utilized to form or break up frozen compositions into
frozen particle compositions, or frozen piercing implements. In one
embodiment, the at least one mechanism includes at least one of
vibration, physical mixing, bubble mixing, or sonication. See, for
example, U.S. Pat. No. 4,704,873, which is incorporated herein by
reference.
[0679] In one embodiment, one or more frozen particle compositions
or frozen piercing implements are made by spraying at least one
fluid composition into at least one freezing chamber by way of at
least one inlet port, whereby as the at least one fluid composition
travels through the chamber, the at least one fluid droplets freeze
into solid particles. In one embodiment, the at least one freezing
chamber includes at least one carrier gas. In one embodiment, the
at least one freezing chamber is held under a vacuum. In one
embodiment, the at least one fluid composition particles travel
through the freezing chamber by at least one force including
gravity, magnetism, electrostatic energy, electromagnetic energy,
centrifugal force, centripetal force, capillary action, hydrophobic
or hydrophilic attraction or repulsion, van der Waals forces, or
other force. In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements are collected by at
least one outlet port. See, for example, U.S. Pat. No. 5,219,746,
which is incorporated herein by reference.
[0680] In one embodiment, one or more frozen particle compositions
or frozen piercing implements are made by utilizing a system for
continuously or serially making and administering the one or more
frozen particle compositions or frozen piercing implements. In one
embodiment, the system includes at least one device for making one
or more frozen particle compositions or frozen piercing implements
and at least one device for administering one or more frozen
particle compositions or frozen piercing implements. In one
embodiment, the system includes at least one hose connecting the at
least one device for making and the at least one device for
administering the one or more frozen particle compositions or
frozen piercing implements. In one embodiment, the system includes
at least one carrier gas. In one embodiment, the at least one
device for administering the one or more frozen particle
compositions or frozen piercing implements includes at least one
handheld or portable device. In one embodiment, the at least one
handheld device includes at least one propulsion gun.
[0681] In one embodiment, the device includes at least one
component for directing administration of the at least one frozen
particle composition or at least one frozen piercing implement. In
one embodiment, the at least one component includes at least one
nozzle. In one embodiment, the at least one nozzle includes at
least one de Laval nozzle.
[0682] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements move at least partially
through the delivery device by way of Venturi effect.
[0683] In one embodiment, one or more frozen particle compositions
or frozen piercing implements are made by utilizing an extrusion
process in a chamber maintained under pressure, and including at
least one carrier gas for administration of the frozen particle
compositions or frozen piercing implements. See, for example, U.S.
Pat. No. 5,666,821, which is incorporated herein by reference.
[0684] In one embodiment, one or more frozen particle compositions
or frozen piercing implements are made by utilizing at least one
cutting mechanism with at least one frozen fluid or frozen
composition substantially in the form of a block, ribbon, sheet, or
other form. See, for example, U.S. Pat. Nos. 5,913,711; and
5,520,572, each of which is incorporated herein by reference.
[0685] In one embodiment, one or more frozen particle compositions
or frozen piercing implements are made by grinding or pulverizing
at least one frozen composition. In one embodiment, at least one
frozen composition is ground with an auger and delivered under
pressure with at least one carrier gas. See, for example, U.S. Pat.
No. 6,174,225, which is incorporated herein by reference.
[0686] In one embodiment, one or more frozen particle compositions
or frozen piercing implements are made by utilizing an ink jet
style printer. See, for example, U.S. Pat. No. 7,306,316, which is
incorporated herein by reference. In one embodiment, the ink jet
style printer utilizes at least one supercooled fluid. In one
embodiment, the supercooled fluid includes at least one cryogenic
fluid. In one embodiment, the ink jet style printer includes a
non-direct contact mechanism for administering the one or more
frozen particle compositions or frozen piercing implements to at
least one substrate. In one embodiment, the ink jet style printer
includes at least one chamber under a vacuum.
[0687] In one embodiment, one or more frozen particle compositions
or frozen piercing implements are made by utilizing a rotary
device. See, for example, U.S. Pat. No. 4,703,590, which is
incorporated herein by reference. In one embodiment, the rotary
device provides at least one mold. In one embodiment, at least one
fluid composition is introduced to the at least one mold, and while
the rotary device rotates through a freezing chamber, the at least
one fluid composition in the at least one mold becomes at least
partially frozen. As the rotary device rotates further, the at
least one frozen particle composition exits the at least one
mold.
[0688] In one embodiment, the one or more frozen particle
compositions or frozen piercing implements are made by utilizing a
"pelletizer." See, for example, U.S. Pat. No. 4,617,064, which is
incorporated herein by reference. In one embodiment, the one or
more frozen particle compositions or frozen piercing implements are
made, for example, by utilizing a holding tank, cooling reservoir,
compressor, and delivery device with a carrier gas. See, for
example, U.S. Pat. No. 6,306,119, which is incorporated herein by
reference.
[0689] In one embodiment, the one or more frozen particle
compositions or frozen piercing implements are made by depositing
at least one fluid composition on at least one support surface. In
one embodiment, a screen-like material, for example, a
nonperforated sheet, strip, or plane receives atomized droplets
(e.g. water droplets), which are then frozen to form ice crystals.
See, for example, U.S. Pat. No. 6,764,493, which is incorporated
herein by reference. In one embodiment, a wire mesh screen moves
through a temperature controlled water bath that coats the mesh
with a thin water layer. Id. In one embodiment, as the mesh enters
the cold environment, ice crystals form and are brushed or scraped
from the mesh with a brush. Id. In one embodiment, temperature and
pressure sensors within the vessel can be used by the control
device to adjust carrier fluid temperature and input pressure.
Id.
[0690] In one embodiment, the one or more frozen particle
compositions or frozen piercing implements are made by extruding at
least one fluid composition through at least one aperture, die or
nozzle. See, for example, U.S. Pat. No. 6,986,265, which is
incorporated herein by reference. In one embodiment, the nozzle
includes at least one de Laval nozzle. In one embodiment, at least
one frozen composition in the form of a ribbon, block, or sheet,
for example, is passed through the at least one aperture, die or
nozzle. In one embodiment, at least one fluid composition is
provided to a freezing chamber configured to freeze the at least
one fluid composition, and subsequently extruded.
[0691] In one embodiment, the one or more frozen particle
compositions or frozen piercing implements are administered to at
least one substrate. In one embodiment, the one or more frozen
particle compositions or frozen piercing implements are
administered by way of compressed gas, blast plate, high-speed
rotor, or electrostatic acceleration (e.g., subatomic
accelerators). See, for example, U.S. Pat. No. 4,945,050, which is
incorporated herein by reference.
[0692] In one embodiment, one or more frozen particle compositions
or one or more frozen piercing implements are made by utilizing
electrospray techniques. In one embodiment, electrospray techniques
are conducted in a vacuum. See, for example, Castro and Bocanegra,
Applied Phys. Lett. vol. 88, pp. 123105-1-123105-3; and U.S. Pat.
No. 2,048,651, each of which is incorporated herein by reference.
In one embodiment, electrospray techniques provide a narrow drop
size distribution, whose mean diameter can be controlled from at
least tens of nanometers to at least hundreds of microns. Id. In
one embodiment, two concentric needles are fed with the conducting
fluid and non-aqueous fluids through inner and outer needles,
respectively. Id. In one embodiment, when an electric field is
applied, the free charges in the conducting fluid migrate to the
interface with the non-aqueous fluid. Id. In one embodiment, the
flow-rates fed to the needles is controllable, which allows for
varying contributions from the conducting fluid or non-aqueous
constituents. Id. In one embodiment, colloidal propulsion
efficiency depends on the ratio of mass vs. charge of the droplets.
Id. When a conducting fluid surface is charged to a sufficiently
high electrical potential, the interface generally forms a cone,
usually referred to as a Taylor cone. Id. A Taylor cone of hydrogen
oxide held in a vacuum freezes almost immediately. Id. However,
when the conducting liquid includes hydrogen oxide, and the
non-aqueous fluid includes at least one oil, a Taylor cone exists
in a vacuum without freezing. Id. Thus, electrospray conditions can
be modified according to the constituents of the frozen particle
compositions, or frozen piercing implements.
[0693] In one embodiment, electrospraying is conducted by exposing
fibers of viscous fluid composition to static electricity having
one pole electrically connected with the fluid composition and the
opposite pole electrically connected with at least one collection
surface. See, for example, U.S. Pat. No. 2,048,651, which is
incorporated herein by reference. In one embodiment, the viscous
fluid composition includes a cold fluid composition. In one
embodiment, the collection surface is approximately at or below the
freezing point of the at least one fluid composition.
[0694] In one embodiment, one or more methods described herein can
be utilized for fabricating one or more of frozen piercing
implements, frozen piercing implement devices, including but not
limited to frozen piercing implement arrays, fluidic devices, or
injection devices, or other associated frozen tools and devices
thereof.
[0695] As described herein, general fabrication techniques can be
utilized, or adapted for making frozen particle compositions,
including frozen piercing implements. Examples of such fabrication
techniques include form-molding, etching, deposition,
micromachining, and freeze-mixing. In one embodiment, the one or
more frozen piercing implements are fabricated by utilizing
multiple processes.
[0696] In one embodiment, one or more frozen piercing implements
are fabricated by utilizing electrochemical etching. In one
embodiment, a frozen composition (e.g., in block, ribbon, or sheet
form) is masked for areas of piercing implements, and etched
utilizing at least one electrolytic solution. In one embodiment,
the electrolytic solution is cold, to prevent disintegration or
dissolution of the frozen composition. In one embodiment, the
electroylytic solution includes at least one of sodium, potassium,
fluoride, chloride, bromide, calcium, magnesium, hydrogen
phosphate, or hydrogen carbonate.
[0697] In one embodiment, one or more frozen piercing implements
are formed by splintering or abrading a frozen composition. For
example, a frozen composition block or ribbon can be splintered or
abraded by utilizing a machine that includes at least one abrading
wheel, or annular splint carrier. See, for example, U.S. Pat. No.
1,613,623, which is herein incorporated by reference.
[0698] In one embodiment, frozen piercing implements are formed by
utilizing a frozen composition and a lithography process. In one
embodiment, the lithography process includes at least
photolithography. In one embodiment, the lithography process
includes at least electron beam lithography. In one embodiment,
etching includes wet etching or dry etching. For example, wet
etching can utilize chemicals alone or in combination with an
energy source, to at least partially remove material surrounding a
device, or to remove one or more layers from the surface of the
material to be etched. In one embodiment, the frozen composition is
a film or block.
[0699] In one embodiment, etching includes plasma etching or
reactive ion etching. For example, reactive ion etching includes
introducing at least one etching gas into the chamber with the
composition to be etched. In one embodiment, plasma is created by
radiofrequency power, and reactive species (radicals and ions) are
generated in the plasma. In one embodiment, reactive species
diffuse onto the surface of the composition, while byproducts from
the chemical reaction are desorbed and exhausted from the chamber.
In one embodiment, the reactive ion etching system includes at
least one of a parallel plate etching configuration with at least
one electrode (e.g. 5 inch quartz electrode), and at least one
radio frequency generator (e.g. 1 kW, 15 MHz). See, for example,
U.S. Patent Application Publication No. 20020193754, which is
herein incorporated by reference. In one embodiment, the system
further includes at least one of a mass flow controller, throttle
valve, controller, or vacuum pump. Id. In one embodiment, reactive
ion etching removes at least one layer of material to be
etched.
[0700] In one embodiment, etching includes isotropic etching or
anisotropic etching. In one embodiment, undercutting is used to
remove material from under a mask. In one embodiment, undercutting
is conducted with at least one of a chemical, a mechanical force,
an electromagnetic force, an electrical force, a thermal change, or
a combination thereof. In one embodiment, undercutting is conducted
with a laser, or fluid jet beam. In one embodiment, undercutting is
conducted by a thermal source (including but not limited to
conduction, convection, or radiation).
[0701] In one embodiment, a masking material is deposited onto a
frozen composition and patterned into dots having a diameter
approximately equal to the base of the desired frozen piercing
implements. The frozen composition is then subjected to etching by
a standard method, some of which are described herein. The regions
protected by the mask remain and form the frozen piercing
implements. In one embodiment, the mask is insulative. In one
embodiment, the mask is heated or chemically treated. In one
embodiment, etching continues until the mask falls off due to
underetching, thereby generating an array of frozen piercing
implements.
[0702] In one embodiment, a "donut-shaped" mask is utilized to etch
hollow frozen piercing implements with inner and outer walls being
etched simultaneously. See, for example, U.S. Pat. No. 6,334,856,
which is incorporated herein by reference.
[0703] In one embodiment, a robotic array-spotting device (e.g.,
DNA microarrayer) is utilized to generate droplets. See, for
example, Park et al., Biomed Devices, vol. 11, pp. 129-133 (2009),
which is incorporated herein by reference. In one embodiment, the
droplets are approximately uniform in size or position. In general,
microarrayers can generate many identical liquid droplets on a
support structure. Id. In addition, the droplets generally have
high resolution and droplet volume can be controlled. Id. In one
embodiment, a microarrayer can generate greater than approximately
one thousand droplets per square centimeter. Id. Subsequently, the
droplets are frozen, and fabricated into frozen piercing
implements. In one embodiment, a channel network is made by placing
a thin wire (e.g., metal wire) on a flat surface, dropping droplets
onto the wire, and freezing the droplets, forming wells along the
wire channel. Id. In one embodiment, the channel network is
utilized in at least one array device, or fluidic device described
herein.
[0704] In one embodiment, frozen piercing implements are fabricated
by utilizing a micromold having tapered walls. For example, a
micromold can be made, for example, by molding a pre-existing
3-dimensional array of microneedles or other piercing implements.
The micromold is then surface plated or coated by, for example,
vapor deposition of one or more constituents. In one embodiment, at
least one constituent is spin-cast in the micromold and frozen. In
one embodiment, a micromold can be made, for example, by laser
ablation techniques.
[0705] In one embodiment, the constituents of the composition
(i.e., at least one fluid and at least one agent) are combined and
blended in at least one polymer (e.g., cellulose, polylactic acid,
polyglycolic acid, or copolymers thereof, etc.), binder, or
pharmaceutical carrier or excipient. Next, the composition is spun
in a mold (e.g., a micromold or nanomold), defining at least one
cavity at 3000 rpm for 5 minutes. See, for example, Oh and Kwon,
CRS conference presentation (2007), available on the worldwide web
at: theraject.com/files/Demonstration_of
Dose-controlled_Delivery_by_Dissolvable_Micro-needle Arrays.pdf,
the content of which is incorporated herein by reference. In one
embodiment, at least two cavities of the mold are loaded with at
least two different compositions. Next, the compositions are at
least partly frozen prior to, during, or subsequent to
spin-casting. The composition on the exterior of the cavities is
optionally removed following centrifugation. Id. In the spun-cast
system, the higher density substances will be forced toward the top
(e.g. tip) of the piercing implements. Id. Devices including at
least one frozen piercing implement can also be fashioned, for
example, utilizing a mold (e.g., micromold, or nanomold). See, for
example, Park et al, Ibid.
[0706] In one embodiment, for example, the mold is fabricated from
an epoxy (e.g. using high-aspect-ratio SU-8 epoxy photoresist
master structures to form polydimethyl siloxane molds). In one
embodiment, injection molding is utilized for fabricating the
piercing implements from the molds. Id. In one embodiment, an
asymmetric masking process during etching of the mold is utilized
to form beveled or other shaped tips. Id. In one embodiment,
microlenses are utilized for fabricating the molds (which can be
altered by changing the focal point of the microlens). Id.
[0707] In one embodiment, the frozen piercing implement support
structure includes a hydrophobic, super hydrophobic, omniphobic,
hydrophilic, or amphiphilic surface. In one embodiment, the support
structure includes a polymeric surface. In one embodiment, the
support structure includes one or more of glass, plastic, metal, or
at least one frozen material. In one embodiment, the support
structure includes at least one of silicon, copper, silver, gold,
platinum, rubidium, or polytetrafluoroethylene.
[0708] In one embodiment, the surface of a support structure is
coated with a fluid (including a viscous form) of at least one
constitutent of the final frozen implement. In one embodiment, a
mold or frame is configured with at least one characteristic for
fabricating the piercing implement. For example, the at least one
characteristic may include but not be limited to the desired size,
shape, optional one or more ports, outer diameter, inner diameter
(for hollow or partially hollow implements), length, inclination
angle of at least one side, array pattern, etc. In one embodiment,
the mold or frame is includes a comb-like configuration. In one
embodiment, the mold or frame is then drawn into the fluid
constituent material. In one embodiment, the mold or frame itself
is coated with the fluid constituent material. In one embodiment,
the fluid constituent material is frozen while it is drawn with the
mold or frame. In one embodiment, the drawing process is carried
out by fixing the support structure and moving the mold or frame
upward or downward, or by fixing the mold or frame, and drawing the
support structure upward or downward. In one embodiment, at least
one desired characteristic of the piercing implements can be
fabricated by varying the drawing speed, or by shaping or cutting
with a mechanical cutter, electrical cutter, magnetic cutter,
thermal cutter, or cutter of another source. In one embodiment, the
cutter includes a laser beam.
[0709] In one embodiment, the frozen piercing implements are
evaporated before removing from the mold or frame. In one
embodiment, at least one additional layer is applied to the frozen
piercing implements by, for example, vapor deposition, spray
coating, dip coating, or other process.
[0710] In one embodiment, the frozen piercing implements are
removed from the mold or frame by varying the humidity, pressure,
or temperature of the piercing implements or the mold or frame. In
one embodiment, the mold or frame is heated to release the
implements. In one embodiment, the mold or frame is fashioned such
that it can be adapted to be heated by electrical, mechanical,
thermal, electromagnetic, or other source of heat. In one
embodiment, the mold or frame includes a hand-in-glove
configuration.
[0711] In one embodiment, at least one heater heats the mold or
frame by way of conduction, convection, or radiation. In one
embodiment, the mold or frame is coated (for example, with a
polymer, oil, wax, film, etc.) for easier removal of the piercing
implements. In one embodiment, the mold or frame is coated with
polytetrafluoroethylene.
[0712] In one embodiment, the frozen piercing implements are
removed from the mold or frame by applying at least one solvent to
the mold, frame, or frozen piercing implements. In one embodiment,
the solvent includes a liquid form of at least one constitutent of
the frozen piercing implement. In one embodiment, the solvent
includes a salt solution. In one embodiment, the solvent includes
an aqueous or non-aqueous fluid.
[0713] In one embodiment, the frozen piercing implements are
removed from the mold or frame by applying at least one of
mechanical energy, electrical energy, electromagnetic energy,
magnetic energy, or thermal energy. In one emobodiment, the frozen
piercing implements are removed from the mold or frame by applying
one or more of a vibrational force, torisonal force, compressive
force, rarefaction force, or contact force (including but not
limited to a collision force, such as an elastic collision or
inelastic collision). In one embodiment, the frame or mold includes
a portion with at least one energy producing or energy conducting
component. In one embodiment, the frame or mold is stacked together
in a sandwich configuration with at least one energy producing or
energy conducting component layer in between. In one embodiment,
the energy producing or energy conducting component includes a mesh
electrical mat. See, for example, U.S. Pat. No. 7,241,979, which is
incorporated herein by reference. In one embodiment, the mold or
frame includes at least one thermoregulator or other regulator. In
one embodiment, the energy producing or energy conducting component
includes at least one thermoregulator or other regulator.
[0714] In one embodiment, the frozen particle compositions, or
frozen piercing implements are fabricated by vapor condensation or
deposition onto a support surface, including but not limited to a
cryo-surface. See, for example, Hallbrucker et al, J. Phys. Chem.
93, pp. 4986-4990 (1989); and Mayer and Pletzer, J. Chem. Phys. 80
(6) pp. 2939-2952, each of which is incorporated herein by
reference. In one embodiment, the cryo-surface includes a cryoplate
or cryowire. For example, samples of amorphous solid water are
prepared by depositing water vapors from a reservoir of hydrogen
oxide held at room temperature through a fine metering valve and a
tume into a high vacuum system, where the hydrogen oxide is
condensed on a copper structure precooled to approximately 77K
(approximately -196.degree. C.). Id. In one embodiment, a baffle is
used above the entrance tube to avoid supersonic flow of the
hydrogen oxide vapor, which can cause rough surfacing of the
particles. Id. In one embodiment, a supersonic flow of the hydrogen
oxide vapor is desired, and no baffle is used. For example, in the
absence of a baffle, supersonic expansion by adiabatic cooling
gives a frozen amorphous solid particle with pores or voids, which
allow for other fluids, including but not limited to inert gases
(e.g., oxygen, nitrogen, or helium), to be adsorbed or enclosed
within the frozen particle composition. Id. For example, the
microporous structure allows amorphous ice a large ability to trap
gases within the solid frozen particle composition. See, for
example, Westley, et al., J. Chem. Phys. vol. 108, pp. 3321-3326
(1998), which is incorporated herein by reference.
[0715] In one embodiment, a method of making a frozen particle
composition, including a frozen piercing implement, includes a
standard refrigeration mechanism for cooling or supercooling at
least one fluid constituent. For example, one form of standard
refrigeration for freezing fluids includes a helix of stacked pipe
coils surrounding and supporting a central support member having a
hollow core, covered by a sleeve member. See, for example, U.S.
Pat. No. 4,351,157, which is incorporated herein by reference.
[0716] In one embodiment, the pipe helix includes an evaporator and
includes a metal, such as copper. Id. In one embodiment, the hollow
central support member includes an insulating material, such as
foam or plastic. Id. In one embodiment, the sleeve member includes
a highly thermally conductive material, such as aluminum. Id. In
one embodiment, the sleeve member is in substantial surface contact
with the outer surface of the pipe helix. Id. Other standard
refrigeration components are disposed in housing and can include at
least one of a compressor, expansion valve, filtering and drying
element liquid receiving means, condenser, or condenser fan. Id. In
one embodiment, the refrigeration means utilizes standard
refrigerating fluids, such as FREON.RTM.. Id. In one embodiment,
the helix of coils surrounded by a thermally conductive metal in
substantial surface contact with the stack of coils results in
formation of a frozen layer on the outer surface of the thermally
conductive sleeve, even in environments not otherwise conducive to
formation of frozen compositions, or frozen piercing implements.
Id. This frozen layer on the outer surface of the thermally
conductive sleeve can be etched, cut, or otherwise fabricated into
frozen particle compositions, or frozen piercing implements.
[0717] In one embodiment, the frozen composition utilized for
fabricating frozen particle compositions, or frozen piercing
implements is exposed to conditions for a time sufficient to at
least partially thaw the frozen composition. Subsequently, the at
least partially thawed composition is frozen solid again. In one
embodiment, the freeze-thaw-freeze alters the surface of the frozen
composition. See, for example, U.S. Pat. No. 1,891,230, which is
incorporated herein by reference. In one embodiment, the altered
surface includes a hardened outer surface, or "crust." Id. In one
embodiment, the frozen composition is embossed or stamped in order
to fabricate at least one frozen particle composition, or frozen
piercing implement. Id. In one embodiment, the frozen composition
undergoes at least one thaw or partial thaw while contacting the
embossing or stamping mold or equipment. In one embodiment, the
frozen composition is exposed to at least one additional freezing
temperature while contacting the embossing or stamping mold or
equipment. In one embodiment, the embossing or stamping mold or
other equipment is heated while contacting the frozen composition.
In one embodiment, the frozen composition is positioned on a
surface, and the embossing or stamping occurs from one side or one
direction. In one embodiment, the frozen composition is positioned
so as to "thread" through an embossing or stamping device, wherein
the embossing or stamping occurs from more than one side or more
than one direction. In one embodiment, the frozen particle
compositions, or frozen piercing implements are collected
subsequent to the embossing or stamping. Id. In one embodiment, the
frozen particle compositions, or frozen piercing implements, are
collected into a cryofluid or refrigerant. In one embodiment, the
frozen particle compositions, or frozen piercing implements, are
collected in at least one compartment. In one embodiment, the at
least one compartment includes at least one refrigerant or
cryogenic fluid. In one embodiment, the at least one compartment
includes at least one of liquid nitrogen, liquid Freon.RTM., liquid
oxygen, or supercooled fluid.
[0718] In one embodiment, the frozen piercing implement includes a
sidewall, or shaft, as shown in FIGS. 121, 126, and others. In one
embodiment, the angle of the sidewall, or angle of the piercing
implement tip, includes at least one of at least approximately
0.degree., approximately 5.degree., approximately 10.degree.,
approximately 20.degree., approximately 30.degree., approximately
40.degree., approximately 45.degree., approximately 50.degree.,
approximately 60.degree., approximately 70.degree., approximately
80.degree., approximately 90.degree., or any value therebetween or
greater.
[0719] In one embodiment, an apparatus is used for preparing frozen
hydrogen oxide particle compositions. See, for example, Mayer and
Pletzer, Ibid. For example, in one embodiment, frozen particle
compositions are prepared by admitting hydrogen oxide vapor from a
reservoir of liquid hydrogen oxide at room temperature, through a
needle valve and a nozzle into a high vacuum system, condensing the
vapor on a support structure precooled to approximately 77 K
(approximately -196.degree. C.). Id. In the apparatus, vapor is
condensed directly in the sealed bottom part of a 10 mm diameter
glass tube. Id.
[0720] In one embodiment, the frozen particles are prepared in
situ, and devitrification is conducted in the presence of gas or in
vacuo. Id. In one embodiment, the apparatus allows for observation
of the devitrification either in vacuo without any prior contact of
the hydrogen oxide with inert gas, or in the presence of various
inert noncondensible gases (99.99% purity). Id.
[0721] In one embodiment, the apparatus includes copper tubes of
various lengths (with 13 and 4 mm inner diameter) used as nozzles.
Id. Various nozzle shapes can be used. Id. Additionally, the
apparatus includes an optional baffle or deflector, such as a
copper plate held at room temperature between the neozzle exit and
the cryoplate. Id. In one embodiment, an oil diffusion pump with
130 l/s pumping capacity is used, with a base pressure of 10.sup.-5
and 10.sup.-6 mbar during condensation. Id. The hydrogen oxide
condensates can be transferred from the copper cryoplate into
liquid nitrogen, and subsequently with a liquid nitrogen cooled
spoon to an analytical instrument, or other location. Id.
[0722] In one embodiment, frozen hydrogen oxide particle
compostions were prepared by condensation of gas evaporating from a
surface of ice Ih at approximately 210 K (approximately -63.degree.
C.), with a chloroform slush bath. Id. In one embodiment, the
coolfinger apparatus is inserted into a large tube with a sealed
flat bottom for the crystalline ice reservoir, without the need for
the nozzle. Id.
[0723] In one embodiment, differential thermal analysis of a sample
of the resulting frozen hydrogen oxide particle compositions is
conducted are conducted using standard techniques. Id. In one
embodiment, the samples are heated from between approximately 83 K
(approximately -190.degree. C.) and approximately 90 K
(approximately -183.degree. C.) with 6 degrees/minute as a heating
rate. Id.
[0724] In one embodiment, frozen particle compositions including at
least, for example, methanol, toluene, butanol, ethanol, pentanol,
or isopropylbenzene are prepared in the same manner, utilizing the
apparatus as depicted in published studies. Id.
[0725] In one embodiment, the size, morphology, or porosity can be
modulated by altering the temperature, pressure, or angle of
incidence for which the vapor is deposited. See, for example,
Hallbrucker et al, Ibid. In one embodiment, including at least one
second fluid with the frozen particles during an annealing process,
results in incorporation of the at least one second fluid in the
frozen particle compositions, or frozen piercing implements. Id.
For example, on heating amorphous solid water from approximately
77K (approximately -196.degree. C.) a decrease in surface area
occurs and sintering proceeds as pores close and become isolated.
Id. In one embodiment, for example, the annealing process is
carried out in the presence of nitrogen or other gases, and the
adsorbed gases become enclosed in the pores during sintering. Id.
The gas cannot be removed by pumping at low temperatures, but is
gradually given off during the warming of the sample up to
approximately 273 K (approximately 0.degree. C.). Id. Accordingly,
the frozen particle compositions, or frozen piercing implements
that include at least one second fluid generally retain a larger
size than the frozen particle compositions, or frozen piercing
implements that do not contain an additional fluid. Id.
[0726] In one embodiment, at least one of the vapor deposition
process or the annealing process is at least partially conducted in
a vacuum, which generates frozen particle compositions, or frozen
piercing implements at least substantially without other gases
present in the frozen particle compositions, or frozen piercing
implements. Id.
[0727] In one embodiment, ice Ic is formed by heating amorphous
solid water or hyperquenched glassy water to approximately 150 K to
approximately 162 K (approximately -123.degree. C. to approximately
-111.degree. C.). Id. In one embodiment, a reversible glass to
liquid transition occurs with an onset temperature of approximately
136 K+/-1 K (approximately -137.degree. C. +/-1.degree. C.) with a
range of transition of approximately 14 K, or 14.degree. C., and
the increase in heat capacity is approximately 1.9 +/-0.2 J/Kmol.
Id. In one embodiment, the heat of crystallization of amorphous
solid water to ice Ic is approximately -1.29+/-0.01 kJ/mol. Id.
[0728] In one embodiment, for example, published studies have shown
that hydrogen oxide prepared at a temperature lower than
approximately 140 K (approximately -133.degree. C.) include
amorphous granules in submicrometer size. See, for example, Boxe et
al., Abstract, J Colloid and Interface Sci. Vol. 309 pp. 412-418
(2007), which is incorporated by reference herein. In one
embodiment, for example, at near 180-200K (approximately
-93.degree. C. approximately -73.degree. C.), solid hydrogen oxide
produces hexagonal or cubic granules or particles in micrometer
size or smaller. Id. Ice particle size can be increased, for
example, by brief annealing at even warmer temperatures to sizes
approaching approximately 10 .mu.m. Id. In one embodiment, the
particle size or phase is monitored or controlled. For example,
environmental scanning electron microscopy can be used to assess
particle size and phase of particles that develop from the vapor
deposition process. Id. In one embodiment, the specific surface
area of particles can be determined from BET (Brunauer, Emmett, and
Teller) analysis of gas adsorption isotherms, as well as other
methods. Id. In one embodiment, the BET analysis includes gas
adsorption of isotherms in the temperature range from approximately
83.5 to 261 K (approximately -190.degree. C. to -12.degree. C.).
Id. As indicated in published studies, the specific surface area of
particles generated by vapor deposition were approximately 102
m.sup.2/g at approximately 83.5K (approximately -190.degree. C.) to
approximately 0.87 m.sup.2/g at approximately 150K (approximately
-123.degree. C.), indicating that a transition from amorphous to
crystalline form of hydrogen oxide occurs at approximately 150K
(approximately -123.degree. C.).
[0729] In one embodiment, frozen particle compositions, or frozen
piercing implements are prepared in a cryopumped ultra-high vacuum
chamber capable of reaching a base pressure of approximately
1.times.10.sup.-10 Torr, as published by Westley et al Ibid. In one
embodiment, ice films are grown on an optically flat gold electrode
of a quartz crystal resonator for a microbalance. Id. For example,
the crystal holder is attached to a closed-cycle refrigerator and
surrounded by two heat shields at approximately 30 K (approximately
-243.degree. C.) and 60 K (approximately -213.degree. C.),
respectively. Id. The films are formed by flowing degassed
high-purity apor through an array of 0.5 mm long, 50 .mu.m diameter
capillaries approximately perpendicular to the gold surface. Id.
Films of thickness between approximately 0.01 .mu.m and
approximately 3 .mu.m were grown at rates in the range of 0.6
nm/minute to 2 nm/minute at support structure temperatures of
approximately 30 K (approximately -243.degree. C.) to 140 K
(approximately -133.degree. C.). Id. In one embodiment, morphology,
density and porosity of frozen particle compositions can be varied
according to one or more of the constitution of the support
structure, the direction of the fluid flow, or the vacuum
conditions. Id.
[0730] In one embodiment, varying the angular distribution of the
incident vapor molecules to the support structure controls the
morphology or porosity of the frozen particle compositions. See,
for example, Stevenson, et al., Science vol. 283, pp. 1505-1507
(1999). For example, in one embodiment, vapor deposited on a
support structure by collimated, effusive hydrogen oxide beams have
a region of uniform thickness (umbra) surrounded by a region of
decreasing thickness (penumbra), whereas vapor deposited on a
support structure by ambient vapor are uniform across the entire
sample, as verified by Auger electron spectroscopy and
temperature-programmed desportion. Id. In one embodiment, the
deposition rates of hydrogen oxide vapor on a support structure
include 0.02 to 0.12 bilayer per second, where 1 bilayer is
approximately equal to 1.1.times.10.sup.15 molecules per square
centimeter). Id. In one embodiment, adsorption of gas (e.g.,
oxygen, argon, or nitrogen) by amorphous solid water frozen
particle compositions, or frozen piercing implements grown with a
deposition angle less than or equal to approximately 20.degree. is
similar to the adsorption by a crystalline ice film. Id. In one
embodiment, adsorption of gas by amorphous solid water frozen
particle compositions, or frozen piercing implements grown with a
deposition angle greater than approximately 30.degree. C. increases
markedly, reaching a maximum when the angle of deposition is
approximately equal to 70.degree. C. Id. At the maximum gas
adsorption, amorphous solid water adsorbs more than 20 times the
amount of gas adsorbed by a crystalline ice film. Id.
[0731] In on embodiment, morphology, density, or porosity can be
controlled by the angle of incidence of the vapor particles
contacting the support structure, as illustrated by ballistic
deposition. Id. For example, the formation of porous, columnar
films by oblique deposition has been demonstrated to be
controllable for a variety for structurally-stable, high-melting
point solids, including but not limited to metals, oxides, or
semiconductors. Id. Accordingly, for preparation of frozen particle
compositions, or frozen piercing implements, morphology, density,
or porosity can be controlled by angle of vapor deposition from
approximately straight-line trajectories that yield less porous
surfaces to an increasing or decreasing angle of deposition, that
result in films of varying thicknesses and growth rates, providing
a shadow of particular background regions of the support structure.
Id.
[0732] In one embodiment, frozen particle compositions, or frozen
piercing implements are prepared by controlling the pressure and
temperature of hydrogen oxide, or other particle composition
constitutent, introduced as a liquid, gas, or solid. In one
embodiment, ice Ic is prepared by hyperquenching pure hydrogen
oxide droplets onto a cold substrate (below approximately 190 K, or
approximately -83.degree. C.), as described herein.
[0733] In one embodiment, ice Ic is prepared by freezing hydrogen
oxide clusters (approximately 6.6-5.5 nm) at 200 K (approximately
-73.degree. C.), or by homogenous freezing at approximately 235 K
(approximately -38.degree. C.) of an emulsion of hydrogen oxide
droplets in an oil matrix. See, for example, Murray and Bertram,
Phys. Chem. Chem. Phys. vol. 8, pp. 186-192 (2006), which is herein
incorporated by reference.
[0734] In one embodiment, emulsions of pure hydrogen oxide droplets
are prepared by mixing distilled, filtered hydrogen oxide with an
oil phase in a proportion of approximately 30-40% water in oil (by
mass). Id. In one embodiment, the oil phase includes approximately
10% surfactant (such as lanolin) in hydrocarbon oil (such as
paraffin oil). Id. In one embodiment, emulsions are cooled to
approximately 173 K (or approximately -100.degree. C.) at a rate of
approximately 10 K (or degrees Celsius)/minute, while monitoring
ice reflection (with the diffraction angle of approximately
24.degree. or approximately)40.degree.. Id. In one embodiment, the
freezing range of pure hydrogen oxide is between approximately
237.5 +/-1 K and 230.4 +/-1 K (approximately -35.6.degree. C.
+/-1.degree. C. and -42.75.degree. C. +/-1.degree. C.), which
indicates that neither the oil nor surfactant significantly alters
the nucleation process of the freezing droplets. Id.
[0735] In one embodiment, the mixture is agitated for 5-10 minutes
or until the droplets are of the desired size, which can be
determined by standard techniques, such as optical microscopy. Id.
Droplet size can be varied by adjusting the agitation time, and
droplet size allows for selection of ice structure with nearly all
frozen particles existing as ice Ic at a volume median diameter of
approximately 5.6 .mu.m. Id. Ice Ic is stable in the emulsions, as
in other contexts, below approximately 240 K (approximately
-33.degree. C.), when it undergoes a solid state transformation to
ice Ih (unless formed in nanoporous material). Id. In one
embodiment, selecting for ice Ic during crystallization of hydrogen
oxide can be conducted by keeping the rate of heat dissipation
greater than the rate of heat production by the crystallization
process. Id.
[0736] As with other methods of preparing frozen particle
compositions, or frozen piercing implements, the structures of the
frozen particle compositions, or frozen piercing implements
prepared in this manner can be analyzed by standard techniques,
including for example, x-ray diffraction. Id.
[0737] In one embodiment, the frozen particle compositions, or
frozen piercing implements are made by contacting at least one
sterile first fluid droplet with at least one surface. In one
embodiment, the at least one surface includes at least one
hydrophobic, super hydrophobic, or omniphobic surface. In one
embodiment, the at least one sterile first fluid droplet changes in
density while the fluid solidifies or freezes. In one embodiment,
the at least one droplet is exposed to at least one force. In one
embodiment, the at least one force includes one or more of
gravitational force, centrifugal force, centripetal force, magnetic
force, electromagnetic force, capillary action, surface tension,
expansion force, pneumatic force, air pressure, fluid pressure,
electromotive force, or electrical force. In one embodiment, as the
droplet density changes, at least one frozen projection is formed.
In one embodiment, the at least one frozen projection includes a
hollow tube through which supercooled fluid passes and freezes at
the tip, thereby growing the at least one projection. In one
embodiment, the at least one frozen projection forms by way of
reverse sublimation. In one embodiment, the at least one frozen
projection forms in accordance with the Bally-Dorsey model. See,
for example, Libbrecht and Lui, on the worldwide web at:
its.caltech.edu/.about.atomic/snowcrystals/icespikes/icespikes.ht-
m; and Blanchard, J. Meterology, vol. 8, pp. 268-269 (1951), each
of which is incorporated herein by reference. In one embodiment,
the at least one frozen projection forms by way of
crystallization.
[0738] In one embodiment, the frozen particle compositions, or
frozen piercing implements, are fabricated by pulling a roll or
tube of the composition while increasing the temperature or
pressure on the composition in order to increase the viscosity.
See, for example, Purves, Biophys. J. vol. 29, pp. 523-530 (1980),
which is incorporated herein by reference. For particular
compositions that may have low viscosity, or low tensile strength,
at least one agent can be added to increase these characteristics.
For example, one or more of a polymer, wax, fat, carbohydrate,
protein, gelatin, or other agent can be added to the fluid
composition, for example, hydrogen oxide or another constituent in
order to increase tensile strength.
[0739] In one embodiment, the frozen particle compositions, or
frozen piercing implements are generated by first combining the
constituents, including any additional agents (such as therapeutic
agents, reinforcement agents, abrasives, explosive materials,
adhesive agents, biological remodeling agents, or other agents)
under appropriate conditions. Next, the combined constituents are
freeze dried. As indicated herein, in one embodiment, the frozen
particle compositions, or frozen piercing implements include but
are not limited to mixtures, solutions, suspensions, dispersions,
gels, or other combinations.
[0740] In one embodiment, the frozen particle compositions, or
frozen piercing implements, are fabricated by spinning. In one
embodiment, the frozen particle compositions, or frozen piercing
implements, are fabricated by melt-spinning, dry spinning, gel
spinning, extrusion spinning, electro-spinning, direct spinning, or
wet spinning. In one embodiment, gel spinning is conducted with
DMSO as a solvent, or as part of the spun composition. See, for
example, Fukae et al., Abstract, Polymer Comm., vol. 46, pp.
11193-11194 (2005), which is herein incorporated by reference.
[0741] In one embodiment, the frozen particle compositions, or
frozen piercing implements, are fabricated by embossing or casting.
In one embodiment, molds for embossing or casting are machined,
milled, drilled, or pressed according to standard techniques. In
addition, as described herein, standard lithographic methods can be
used, followed by electroplating or wet/dry etching for preparing
molds. In one embodiment, isothermal embossing is utilized, in
which the constituents and the mold are heated above the glass
transition temperature, and then pressed against the mold. In one
embodiment, non-isothermal embossing is utilized, in which the mold
alone is heated and pressed. As described herein, in certain cases
where the glass transition temperature for a particular frozen
particle composition , or frozen piercing implements is low, the
articles used to make the frozen particle compositions, or frozen
piercing implements are also kept at a low temperature, and heating
any particular article occurs relative to the glass transition
temperature.
[0742] In one embodiment, a frozen piercing implement or frozen
piercing implement device is embossed in a frozen composition. A
mold fabricated from a pre-existing microneedle array, for example,
can be utilized. The micromold is coated with at least one
constitutent by, for example, vapor deposition, and the frozen
piercing implements are etched from the non-embossed side until the
embossed cavity is exposed. See, for example, U.S. Pat. No.
7,344,499, which is incorporated herein by reference. Next, at
least one constituent is deposited on the embossed side and
sidewalls, but not on the non-embossed side. Id. The micromold is
then removed to form the frozen piercing implement(s).
[0743] In one embodiment, the frozen particle compositions, or
frozen piercing implements, are fabricated by injection molding or
rapid-injection molding. In one embodiment, for example, the
combined constituents are injected into a cavity or die, then
cooled under conditions sufficient to solidify the constituents. In
one embodiment, the composition solidifies in a short amount of
time. In one embodiment, the composition solidifies in a longer
period of time. In certain instances, depending on the constitution
of a particular composition, the time from injection to
solidification can be adjusted for specific desired results. See,
for example, U.S. Pat. No. 6,572,796, which is incorporated herein
by reference.
[0744] In one embodiment, the frozen particle compositions, or
frozen piercing implements are made by calendering. In certain
instances, the constituents are combined and placed under
conditions sufficient to solidify the combined constituents
(including but not limited to high pressure or lower temperature)
before or during calendering the combined constituents into a sheet
or layer on a base. Various constituents can be layered together in
multiple layers, or can be combined in a single layer. The frozen
particles can then be further processed to attain the desired size,
shape, etc. by cutting, etching, embossing, or similar
technique.
[0745] In one embodiment, the devices associated with or including
at least one frozen piercing implement, including but not limited
to frozen piercing implement array devices, fluidic devices, or
injection devices, are at least partially fabricated by
micromachining techniques. In one embodiment, surface
micromachining, bulk micromachining, or a combination thereof is
used.
[0746] In one embodiment, the frozen piercing implements are made
by providing at least one fluid composition, and utilizing at least
one force configured to induce at least one projection in the at
least one fluid composition. In one embodiment, the at least one
force includes at least one of: gravitational force, centrifugal
force, centripetal force, magnetic force, electromagnetic force,
capillary action, surface tension, expansion force, pneumatic
force, air pressure, fluid pressure, electromotive force, or
electrical force, or the like.
[0747] In general, the volumetric flow rate Q forming icicle-like
piercing implements is on the order of tens of milliliters per hour
(approximately 0.01 cm.sup.3/second), and icicle radii are
generally in the range of approximately 1-10 cm. See, for example,
Short et al., Phys. Fluids, vol. 18, pp. 083101-1-5, (2006), which
is incorporated herein by reference. As such, a cylindrical icicle
of radius r, has an aqueous film flow of thickness h, and since h
is smaller than r over nearly the entire icicle surface, the
velocity profile in the layer may be determined as that flowing on
a flat surface. Id. If y is a coordinate normal (or approximately
so) to the surface and .theta. is the angle that the tangent vector
.tau. makes with respect to the horizontal, then the Stokes
equation for gravity-driven flow is v.sub.wd.sup.2u/dy.sup.2=sin
.theta., where g is the gravitational acceleration and v.sub.w=0.01
cm.sup.2/second is the kinematic viscosity of hydrogen oxide.
Id.
[0748] Additionally, piercing implements can be made from a single
drop or droplet of at least one fluid composition by applying a
scaling factor or the aspect ratio. Id. For example, dimensionless
profiles can be constructed for a desired form by applying the
formula for the "ideal icicle shape," in accordance with naturally
occurring icicle shapes, which is .rho.=4/3 (.zeta..sup.1/2+2)
.zeta..sup.1/2-1. Id. Likewise, for example, evaluating the
asymptotic form at some point on the surface (.rho.*, .zeta.*)
where the aspect ratio (length/width) is A=.zeta.*/.rho.*, and the
shape can be written as
.zeta./.zeta.*.apprxeq.(.rho./.rho.*).sup.4/3, a universal,
self-similar form, regardless of the droplet size. Id. In this
regard, it is possible to predict or compute parameters for a
frozen piercing implement based on the natural formation of
icicles.
[0749] In one embodiment, acoustic force is utilized to induce at
least one projection from at least one fluid composition. For
example, the shape of a drop or bubble can be distorted, and
internal flow manipulated, by shifting the resonant frequencies of
natural shape oscillations. See, for example, Trinh, et al., Jet
Propulsion Lab white paper, available at the worldwide web at
trs-new.jpl.nasa.govidspace/bitstream/2014/20280/1/98-1182.pdf, the
content of which is incorporated herein by reference.
[0750] In one embodiment, the frozen particle compositions are made
with at least one compound that has been sterilized (e.g., by
filtration, by ultraviolet light, or other method), degassed, or
deionized.
[0751] In one embodiment, at least one first fluid composition is
contacted with at least one second fluid for a time and condition
sufficient to form one or more frozen particle compositions, or
frozen piercing implements as described herein.
[0752] In one embodiment, at least one agent (e.g., a reinforcement
agent) is utilized to freeze with one or more components, or
substances. In one embodiment, the at least one agent is
substantially a solid, and at least one substance or component is
substantially a liquid. The combination is then frozen, and frozen
particle compositions are generated as described herein.
[0753] In one embodiment, one or more frozen particle compositions
or frozen piercing implements are extruded by way of a die, or
molding. In one embodiment, the constituents are combined during
the extrusion process. In one embodiment, a spinneret is utilized
for extrusion of frozen particle compositions or frozen piercing
implements. In certain instances, the compositions are extruded in
a semi-solid state, and then further solidified. In one embodiment,
different dies or extrusion plates are used with the spinneret in
order to form particular cross-sectional shapes (e.g., round,
trilobal, pentagonal, octagonal, etc.). In one embodiment, a
configuration can be used that resists bending of the extrudate,
particularly when the extrudate is composed of multiple
constituents. See, for example, PCT Publication No. WO/2000/070131,
which is incorporated herein by reference.
[0754] In one embodiment, one or more frozen particle compositions,
or frozen piercing implements are generated with assistance of at
least one refrigerant or cryogen, including but not limited to
liquid nitrogen, liquid carbon dioxide, etc.
[0755] In one embodiment, at least one agent (e.g., a reinforcement
agent) is utilized to crystallize one or more components or
substances. The crystallization is frozen, and frozen particle
compositions, or frozen piercing implements are generated as
described herein.
[0756] In one embodiment, the size of at least one frozen particle
composition is measured. In one embodiment, the size of at least
one frozen particle composition is measured according to particle
size distribution. In one embodiment, the frozen particle
composition size may be measured by, for example, sieve analysis,
optical counting methods, electron microscopy, disc centrifugation,
electrozone sensing, dynamic light scattering, electroresistance
counting methods, scanning tunneling microscopy, atomic force
microscopy, sedimentation techniques, laser diffraction methods,
acoustic spectroscopy, ultrasound attenuation spectroscopy, and the
like. In one embodiment, the size distributions are measured, for
example, by utilizing an electrical mobility sizing technique in
accordance with the National Institute of Standards and Technology
Standard Reference Material Particles. See, for example,
Application Note SMPS-003, on the worldwide web at tsi.com; the
subject matter of which is herein incorporated by reference. In one
embodiment, the size distribution of a particular lot of frozen
particle compositions, or frozen piercing implements is measured by
utilizing, for example, a Scanning Mobility Particle Sizer.TM.
(SMPS) spectrometer. Id. For example, the SMPS spectrometer
utilizes a differential mobility analyzer to size classify the
particle stream and a condensation particle counter to determine
the concentration at each size. Id. The differential mobility
analyzer utilizes the fact that a particles' electrical mobility
(Z.sub.p, or the ability of a charged particle to move in an
electric field) is roughly inversely proportional to particle
diameter. Id. Additionally, size distribution measurements can be
made in real-time with the SMPS spectrometer. Id.
[0757] In one embodiment, size distributions of electrospray
droplets from a Taylor cone are directly measured by using a
freezing method and a transmission electron microscope image
processing. See, for example, Ki Ku, et al., Abstract, J. Aerosol
Sci., vol. 32, no. 12, pp. 1459-1477 (2001), which is incorporated
herein by reference.
[0758] In one embodiment, one or more methods, devices, or systems
described herein include delivering or administering one or more
frozen particle compositions, or frozen piercing implements by high
velocity impact. In one embodiment, the one or more devices that
utilize high velocity impact delivery provide at least one of
localized delivery, targeted delivery, sustained delivery,
modulated delivery, feedback controlled delivery. In some
instances, an example of a device that can be used for
administering one or more of the compositions described herein
includes a handheld device, such as a wand, pen, baton, hose,
sprayer, spigot, gun (e.g., particle or pellet gun), or other
device. In certain instances, the device is at least part of a
built-in delivery device, such as can be included in a wall, an
overhead device, a corral, a gate, or a device that includes a
cavity into which a subject can be placed for administration or
delivery of at least one composition described herein. In certain
instances, the device has robotic action. In any of these
instances, the device can be remotely controlled, for example, by a
human, computer system, or computer program. In one embodiment, the
device can be built in, for example, in a room (e.g., hospital
room, surgical room, greenhouse, food or beverage facility, outdoor
or indoor arena or stadium, home, institutions, etc.).
[0759] In one embodiment, a method for making one or more frozen
particle compositions, or frozen piercing implements includes
passing one or more droplets of at least one fluid composition
through a compartment that is configured to provide conditions for
a time sufficient to freeze the one or more droplets; wherein the
compartment includes at least one hydrophobic surface and wherein
the at least one fluid composition includes at least one fluid and
at least one agent. In one embodiment, the at least one hydrophobic
surface is reversible to at least one hydrophilic surface. In one
embodiment, the reversible hydrophobic surface includes at least
one vanadium oxide nanostructured film. See, for example, Lim et
al, J. Am. Chem. Soc., Abstract, vol. 129, pp. 4128-4129 (2007),
which is incorporated herein by reference. For example, fabrication
of a roselike nanostructured vanadium oxide (V.sub.2O.sub.5) film
with photoinduced surface wettability switching can be conducted by
drop-casting a suspension of vanadium oxide particles. Id. In one
embodiment, the suspension of vanadium oxide particles is
synthesized with the sol-gel method. Id. In one embodiment,
alkylamine is added to the vanadium oxide, in such a manner that
alkyl chains are intercalated between the vanadium oxide layers.
Id. The surface is tunable, for example, by exposing the surface to
ultraviolet light, the surface becomes superhydrophilic, while
exposure to darkness renders the surface superhydrophobic. Id.
[0760] In one embodiment, a method for administering at least one
frozen piercing implement to at least one substrate comprises
contacting at least one substrate with at least one frozen piercing
implement.
[0761] In one embodiment, administering the at least one frozen
piercing implement to at least one substrate includes accelerating,
propelling, pushing, pulling, or ejecting the at least one frozen
piercing implement toward the at least one substrate. In one
embodiment, administering the at least one frozen piercing
implement to at least one substrate includes drilling or
administering with a screw-type action. In one embodiment,
administering the at least one frozen piercing implement to at
least one substrate includes accelerating, propelling, pushing,
pulling, or ejecting the at least one substrate toward the at least
one frozen piercing implement. In one embodiment, administering the
at least one frozen piercing implement to at least one substrate
includes propelling, ejecting, pushing, pulling, drilling, or
accelerating the at least one frozen piercing implement toward the
at least one substrate with at least one of a predetermined angle,
predetermined velocity, predetermined force, predetermined
substrate stress, predetermined rate of administration,
predetermined depth, predetermined location, predetermined time
sequence, or predetermined spatial pattern. In one embodiment, the
method further comprises varying the rate, velocity, force, or
angle at which the at least one frozen piercing implement is
administered to the at least one substrate.
[0762] In one embodiment, administering the at least one frozen
piercing implement to at least one substrate includes propelling,
ejecting, pushing, pulling, drilling, or accelerating a plurality
of frozen piercing implements toward the at least one substrate. In
one embodiment, propelling, ejecting, pushing, pulling, drilling,
or accelerating the plurality of frozen piercing implements toward
the at least one substrate includes propelling, ejecting, or
accelerating the plurality of frozen piercing implements at one or
more of a predetermined angle, predetermined velocity,
predetermined rate of administration, predetermined spatial
pattern, predetermined location, predetermined time sequence,
predetermined force, predetermined substrate stress, or
predetermined depth. In one embodiment, two or more of the
plurality of frozen piercing implements each includes at least one
agent that physically or chemically bind upon administration. In
one embodiment, administering the at least one frozen piercing
implement occurs prior to, during, or subsequent to surgery.
[0763] In one embodiment, the method further comprises varying the
rate, velocity, force, or angle at which the at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device is administered to the at least one substrate. In
one embodiment, administering the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device occurs prior to, during, or subsequent to
surgery.
[0764] In one embodiment, the method further comprises
administering to the at least one substrate at least one article
including an optical, photonic, or electronic article. In one
embodiment, the at least one article is configured to communicate
with at least one computer system. In one embodiment, the at least
one article is configured to monitor at least one characteristic of
the at least one substrate. In one embodiment, the at least one
substrate includes at least one biological cell or tissue, and the
at least one characteristic of the at least one substrate includes
one or more of: tissue formation, tissue growth, cell
proliferation, cell differentiation, nuclear division, apoptosis,
dissolution, deterioration, biochemical function of at least one
cell, biochemical function of at least one tissue, biochemical
function of at least one organ, structural integrity, structural
function, immunological reaction, or durability of the at least one
biological tissue.
[0765] In one embodiment, the at least one article includes at
least one temperature-sensitive substance. In one embodiment, the
at least one article is intermixed with the at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment, the at least one article is
located in the at least one frozen piercing implement. In one
embodiment, the at least one article includes at least one
electronic identification device. In one embodiment, the at least
one electronic identification device includes at least one radio
frequency identification device.
[0766] In one embodiment, the at least one article includes at
least one radioactive, luminescent, colorimetric or odorous
substance. In one embodiment, the at least one article is
configured to sense at least one change in temperature. In one
embodiment, the at least one article includes at least one of a
diamagnetic particle, ferromagnetic particle, paramagnetic
particle, super paramagnetic contrast agent, particle with altered
isotope, or other magnetic particle.
[0767] In one embodiment, the method further comprises adjusting
the temperature of the at least one substrate prior to, during, or
subsequent to administering the at least one frozen piercing
implement to at least approximately 37.degree. C., approximately
36.degree. C., approximately 35.degree. C., approximately
34.degree. C., approximately 33.degree. C., approximately
32.degree. C., approximately 31.degree. C., approximately
30.degree. C., approximately 29.degree. C., approximately
28.degree. C., approximately 27.degree. C., approximately
26.degree. C., approximately 25.degree. C., approximately
24.degree. C., approximately 23.degree. C., approximately
22.degree. C., approximately 21.degree. C., approximately
20.degree. C., approximately 19.degree. C., approximately
18.degree. C., approximately 17.degree. C., approximately
16.degree. C., approximately 15.degree. C., approximately
14.degree. C., approximately 13.degree. C., approximately
12.degree. C., approximately 11.degree. C., approximately
10.degree. C., approximately 9.degree. C., approximately 8.degree.
C., approximately 7.degree. C., approximately 6.degree. C.,
approximately 5.degree. C., approximately 4.degree. C.,
approximately 3.degree. C., approximately 2.degree. C.,
approximately 1.degree. C., approximately 0.degree. C., or any
temperature less than or therebetween.
[0768] In one embodiment, contacting at least one substrate
includes at least one of cutting, stitching, cauterizing, freezing,
perforating, penetrating, ablating, or abrading at least a part of
the surface of the at least one substrate. In one embodiment,
administering the at least one substrate occurs in conjunction with
cryosurgery, cryotherapy, or mesotherapy.
[0769] In one embodiment, the method further comprises sensing or
extracting at least one material from the at least one substrate.
Various non-limiting examples of materials that are capable of
being sensed or extracted from at least one substrate are provided
herein.
[0770] In one embodiment, contacting at least one substrate affects
one or more of electrical resistance of the at least one substrate,
or permeability of the at least one substrate. In one embodiment,
the method further comprises withdrawing the at least one frozen
piercing implement from the at least one substrate.
[0771] In one embodiment, a method of vaccinating a subject
includes administering to a subject at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device that includes at least one vaccine. Specific
examples of compositions including frozen piercing implements
including vaccines are described herein.
[0772] In one embodiment, a method includes delivering at least one
agent to at least one substrate, wherein the agent is included as
part of a frozen piercing implement. In one embodiment, a method
for piercing at least one substrate includes piercing at least one
substrate with a frozen piercing implement including at least one
agent. Specific examples of compositions including frozen piercing
implements are described herein.
[0773] In one embodiment, a method for administering a frozen
piercing implement device that includes at least one frozen
piercing implement includes contacting the frozen piercing
implement device (e.g., an array device, fluidic device, or
injection device, etc.) with at least one substrate. In one
embodiment, a method for delivering at least one agent includes
administering at least one frozen piercing implement device to at
least one substrate, wherein at least one frozen piercing implement
of the device includes at least one agent. In one embodiment, the
at least one frozen piercing implement is coated with at least one
agent. In one embodiment, the at least one agent is encapsulated in
the at least one frozen piercing implement. In one embodiment, at
least one frozen piercing implement includes at least one conduit
configured to deliver at least one agent. In one embodiment, the at
least one frozen piercing implement array is administered to at
least one substrate prior to, during, or subsequent to
administering a trans-substrate patch or iontophoretic device. In
one embodiment, the trans-substrate patch includes a transdermal
patch.
[0774] In one embodiment, at least one material is extracted from
the at least one substrate. Various non-limiting examples of
materials that are capable of being extracted from at least one
substrate are described herein. In one embodiment, the at least one
material extracted from the at least one substrate is held in at
least one compartment. In one embodiment, spring means, a
cantilever, gate, expandable balloon, rigid balloon, or other
regulatory means, are configured to cause a change in volume, and
corresponding change in internal pressure, of the compartment. For
example, in one embodiment, the compartment includes a movable,
rigid top with fixed, rigid side walls, wherein the interface
between the walls and top include a gas-tight seal (for example, by
placement of a gasket or other seal). See, for example, U.S. Pat.
No. 7,344,499, which is herein incorporated by reference.
[0775] In one embodiment, at least one material is extracted by way
of an osmotic pump. Id. In one embodiment, a volume expansion or
pressure reduction in the compartment drives the at least one
material into the compartment. In one embodiment, a Luer-Lock
syringe or similar device is used for all sizes of macro-, micro-,
or nano-implements.
[0776] In one embodiment, the at least one first compartment is
configured to hold at least one material extracted from the at
least one substrate. In one embodiment, the at least one second
compartment is configured to hold at least one agent or other
substance to be administered to the at least one substrate. In one
embodiment, the at least one first compartment and the at least one
second compartment are the same compartment, and includes at least
one mode of intaking at least one extracted material, and at least
one mode of expelling at least one agent or other substance (e.g.,
at least one detection material).
[0777] In one embodiment, the at least one agent is configured to
move from the compartment to the substrate by diffusion,
sublimation, explosive force, fracturable membrane, mechanical or
electrical gate, magnetic force, or other means. In one embodiment,
the at least one agent moves from the compartment to the substrate
by means including a pump (e.g., osmotic pump), or a plunger. In
one embodiment, the compartment includes a syringe or pump
connected to the support structure.
[0778] In one embodiment, the frozen piercing implement device
includes a sealing mechanism to assist in maintaining at least one
agent in the compartment until it is ready to be delivered or mixed
with the contents of another compartment. In one embodiment, the
sealing mechanism is a fracturable barrier interposed between the
compartment and the support structure. In one embodiment, the
frozen piercing implement device includes a means for indicating
that administration of the device has been at least initiated or
completed. In one embodiment, the means for indicating includes a
color change. In one embodiment, the frozen piercing implement
device includes, for example, a rate control means, such a as a
semi-permeable membrane, that assists in regulating flow through at
least one frozen piercing implement. In one embodiment, the frozen
piercing implement device includes multiple compartments.
[0779] In one embodiment, the frozen piercing implement device
including at least one frozen piercing implement or portion
thereof, includes a closed-loop delivery system. For example, at
least one agent is delivered at the time of administration of the
at least one frozen piercing implement device to at least one
substrate. Subsequently, at least one material is extracted or
collected from the at least one substrate. In one embodiment, the
at least one material is analyzed by at least one sensor in at
least one piercing implement.
[0780] In one embodiment, the at least one material is analyzed by
at least one sensor in at least one optional compartment. In one
embodiment, a feedback, or closed-loop provides instructions to at
least one controller to dispense at least one agent to the at least
one substrate. See, for example, U.S. Pat. No. 6,256,533, which is
incorporated herein by reference.
[0781] In one embodiment, a method includes affecting electrical
resistance in the outer surface of a subject. For example,
according to published studies, piercing skin with microneedles
causes a 50-fold reduction in the skin's electrical resistance,
which is comparable to the reduction in electrical resistance by
piercing skin with a 30-gauge "macroneedle." See, for example, U.S.
Pat. No. 6,334,856, which is incorporated herein by reference.
[0782] In one embodiment, a method includes affecting the skin
permeability of a subject. For example, solid microneedles inserted
into the skin and left in place create pathways for transport
across the skin, and increase skin permeability. See, for example,
U.S. Pat. No. 7,344,499, which is incorporated herein by reference.
In another example, solid microneedles inserted into skin and then
removed increase skin permeability. Id. In another example, hollow
microneedles inserted into the skin and left in place increase skin
permeability and transport across the skin. Id.
[0783] In one embodiment, at least one detection material is
utilized with the frozen piercing implement device. In one
embodiment, the at least one detection material is located in the
frozen piercing implement. In one embodiment, the at least one
detection material is located in the at least one compartment. In
one embodiment, the at least one detection material is configured
to indicate a color change as the at least one extracted material
contacts the frozen piercing implement. In one embodiment, the at
least one detection material is configured to indicate a color
change as the at least one extracted material contacts the at least
one compartment. In one embodiment, the at least one detection
material is configured to indicate the presence of at least one
extracted material.
[0784] In one embodiment, the at least one detection material is
configured to indicate the depth of administration of the frozen
piercing implement or frozen particle composition. In one
embodiment, the at least one detection material is configured to
indicate the depth of administration of at least one agent
delivered by the frozen piercing implement or frozen particle
composition.
[0785] In one embodiment, the device includes at least one nozzle,
such as a venturi nozzle, de Laval nozzle, or virtual Laval nozzle.
See, for example, U.S. Pat. Nos. 4,038,786; 4,707,951; and
5,779,523, each of which is incorporated herein by reference.
[0786] In one embodiment, the device includes at least one
amplifier to increase the flow or passage of the one or more frozen
particle compositions, or frozen piercing implements through or out
of the device. See, for example, U.S. Pat. No. 4,398,820, which is
incorporated herein by reference. In one embodiment, the device
includes at least one injector, such as an oblique injector, that
allows for introduction of a fluid (e.g., a gas or liquid) to
assist in moving the one or more frozen particle compositions, or
frozen piercing implements through or out of the device. (See, for
example, U.S. Pat. No. 4,555,872, which is incorporated herein by
reference.)
[0787] In one embodiment, administering or delivering the at least
one frozen particle composition, or frozen piercing implement
includes at least one of accelerating, ejecting, or propelling the
frozen particle composition, or frozen piercing implement. In one
embodiment, the at least one frozen particle composition, or frozen
piercing implement is accelerated, ejected, or propelled to or at a
predetermined pressure or predetermined velocity for delivery of
the at least one frozen particle composition or frozen piercing
implement to a desired location on or in the at least one substrate
(e.g., a biological tissue). In certain instances, the at least one
frozen particle composition, or frozen piercing implement is
accelerated, ejected, or propelled at a particular pressure, angle,
or velocity. In certain instances, the at least one frozen particle
composition, or frozen piercing implement is accelerated, ejected,
or propelled at a predetermined pressure, angle, or velocity.
[0788] The angle, velocity or pressure determined for delivery of
the at least one frozen particle composition, or frozen piercing
implement can depend on certain factors, for example, including but
not limited to, size and density of the frozen particle
composition, or frozen piercing implement, content of the frozen
particle composition, or frozen piercing implement, desired effect
or outcome of administration of the frozen particle composition, or
frozen piercing implement, density of the target tissue, density of
surrounding tissue, type of tissue, architecture of the tissue, and
other factors. In certain instances, the desired angle, velocity or
pressure for accelerating, ejecting, or propelling the at least one
frozen particle composition, or frozen piercing implement described
herein will be the minimum angle, velocity or pressure needed to
achieve desired penetration of the substrate (including a
biological tissue) with the frozen particle composition, or frozen
piercing implements whether for surface abrasion, therapeutic
delivery, or other goal.
[0789] In addition to the angle and velocity of accelerating,
ejecting, or propelling the at least one composition, other factors
can affect the depth of penetration of a particular composition,
including, for example, one or more characteristics of the
particular composition (e.g., size, shape, or constitution of the
frozen particle composition, or frozen piercing implement) or one
or more characteristics of administration of the particular
composition (e.g., the quantity of frozen particle compositions, or
frozen piercing implements administered, distance between the
delivery device and the target substrate).
[0790] The means for accelerating, ejecting, or propelling the one
or more frozen particle compositions, or frozen piercing implements
described herein are non-limiting, and may include general methods
for making, formulating, and delivering the one or more frozen
particle compositions, or frozen piercing implements. For example,
the one or more frozen particle compositions, or frozen piercing
implements may be delivered to at least one substrate (such as a
biological tissue) by carrier gas under pressure, mechanical or
electrical impulse assistance, centripetal or centrifugal force, or
others, some of which are described herein. (See e.g., U.S. Pat.
No. 4,945,050 and PCT application WO 92/01802, each of which is
incorporated herein by reference). In certain instances, the one or
more frozen particle compositions, or frozen piercing implements
are made, propelled, accelerated, or ejected simultaneously. Thus,
the frozen particle compositions, or frozen piercing implements can
be made while propelled, the frozen particle compositions, or
frozen piercing implements can be made while accelerated, the
frozen particle compositions, or frozen piercing implements can be
made while ejected, or any combination thereof.
[0791] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements are delivered or
administered by utilizing a carrier fluid. In one embodiment, the
carrier fluid includes a carrier gas. In one embodiment, the
carrier fluid includes a cold fluid, including a super cooled
fluid. In one embodiment, the carrier fluid includes dehumidified
air. In one embodiment, the carrier fluid includes at least one
inert gas. In one embodiment, a method for administering one or
more frozen particle compositions, or frozen piercing implements
includes controlling the density of the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
method further includes monitoring the temperature of at least part
of the substrate to which the one or more frozen particle
compositions, or frozen piercing implements are administered or are
intended to be administered. In one embodiment, the method includes
slowing or stopping the delivering of the one or more frozen
particle compositions, or frozen piercing implements if the
temperature of the at least part of the substrate becomes lower
than at least one preset limit. In one embodiment, the method
includes monitoring the velocity, depth of impact or penetration,
constitution one the one or more frozen particle compositions, or
frozen piercing implements, or other parameter of administration of
the one or more frozen particle compositions, or frozen piercing
implements.
[0792] In one embodiment, the frozen piercing implements include at
least one sensor located at the initial point of contact with at
least one substrate. In one embodiment, the at least one sensor
monitors pressure at the piercing implement tip.
[0793] In one embodiment, the one or more frozen particle
compositions are delivered or administered by an inkjet
printer-type apparatus or device, by a thermal bubble device, by
ultrasound-mediated transdermal drug transport, or by other device.
When a voltage is applied, an inkjet-type apparatus generates a
pressure pulse by change in shape or size of a chamber containing a
fluid (or solid), and the pressure pulse drives the contents from
the chamber. In one particular instance, a high velocity device
(such as a powderject, air guns, or slingshot type devices) is
utilized for administration of at least one frozen particle
composition or frozen piercing implement as described here.
[0794] For example, in one embodiment, at least one frozen particle
composition or frozen piercing implement is propelled by way of a
powderject system, as described by Kumar and Philip (Trop. J.
Pharm. Res., vol. 6, No. 1, pp. 633-644 (2007), which is
incorporated herein by reference). The powderject system utilizes
high-speed gas flow (such as helium) that is usually painless and
causes minimal bleeding or damage to the skin. (See also e.g., Tang
et al., Pharm. Res., vol. 19, pp. 1160-69 (2002), which is
incorporated herein by reference). As described by Kumar and
Philip, particles are contained in a cassette between two
polycarbonate membranes located at the end of a chamber (Kumar and
Philip, Trop. J. Pharm. Res., vol. 6, No. 1, pp. 633-644 (2007),
which is incorporated herein by reference). As described by Kumar
and Philip, the polycarbonate membranes are ruptured when a carrier
gas enters the chamber under high pressure, and the rapid expansion
of the gas forms a shock wave that travels down the nozzle at a
speed of approximately 600-900 m/s. Velocities of up to about 800
m/s at the nozzle exit are reported, and the momentum density of
the particles within the gas flow can be optimized for desired
depth of penetration upon delivery to a biological tissue. (Kumar
and Philip, Trop. J. Pharm. Res., vol. 6, No. 1, pp. 633-644
(2007), which is incorporated herein by reference). In the
powderject system, particle velocity is controlled by nozzle
geometry, membrane burst strength, and gas pressure. (See e.g.,
U.S. Pat. Nos. 5,630,796; and 5,699,880, which are incorporated
herein by reference).
[0795] Metered-dose transdermal sprays may also be used for
delivery of at least one frozen particle composition or frozen
piercing implement, as described herein. As described by Rathbone,
et al., in one particular example, a topical solution containing a
volatile then nonvolatile vehicle including a therapeutic agent is
administered as a single-phase solution. (See Rathbone, et al.,
Modified Release of Drug Delivery Technology, NY, Marcel Dekker,
Inc. vol. 126, pp. 471-619 (2004), which is incorporated herein by
reference). A finite metered-dose application of the formulation to
intact skin results in evaporation of the volatile component,
leaving the remaining nonvolatile penetration enhancer or
therapeutic agent to partition into the stratum corneum and
creating a reservoir of the therapeutic agent(s). See Rathbone,
Ibid; and Kumar, et al., Trop. J. Pharm. Res., vol. 6, pp. 633-644
(2007), each of which is incorporated herein by reference.
[0796] In addition to these particular examples of devices that can
be utilized for administration of the compositions described
herein, the compositions can be administered in conjunction with
other delivery devices. Likewise, the compositions described herein
for abrasion of at least one biological tissue can be delivered to
the at least one tissue by any means described herein. Some such
means for delivery of the compositions described herein include,
but are not limited to, ultrasound, iontophoresis (which involves
applying an electrical potential across skin or other tissue in
order to increase penetration of ionizable agents), diffusion,
electroporation, photomechanical waves (such as by producing pulses
with Q-switched or mode-locked lasers to the skin or other tissue),
needle-free injections, electro-osmosis, artificial vesicles, laser
radiation, magnetophoresis (utilizing a diamagnetic substance for
use with a magnetic field for increased penetration of the
composition into the biological tissue), microscissuining,
controlled heat aided delivery (which involves heating the skin
prior to or during administration), tattoos, three-dimensional
holograms, or etchings.
[0797] In one embodiment, Rathbone et al. have described artificial
vesicles that mimic cell vesicles (such as TRANSFERSOMES.RTM., from
IDEA AG, Germany) can be utilized for administration of one or more
composition described herein. Artificial vesicles penetrate the
skin barrier along the transcutaneous moisture gradient and causes
"virtual" pores between the cells in an organ without affecting its
biological properties. (See, e.g., Modified Release Drug Delivery
Technology, NY, Marcel Dekker, Inc., vol. 126, pp. 471-619 (2004),
which is incorporated herein by reference). In addition, liposomes,
erythrocyte ghosts, and niosomes also serve as carriers and can be
utilized in the administration of at least one frozen particle
composition or frozen piercing implement described herein.
[0798] In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements are generated by
spraying a jet or mist of the composition constituents into a low
temperature environment (solid, liquid, gas, or any combination
thereof) such that the compositions freeze and form frozen
particles. In one embodiment, streams of frozen particles are
extruded at low temperatures through fine ducts and into a low
temperature environment. In one embodiment, the one or more frozen
particles are propelled through a nozzle or other delivery
apparatus. In one embodiment, the one or more frozen particles are
delivered by utilizing flash boiling or BLEVE, or other explosion,
of a cold liquid. In one particular example, liquid nitrogen is
flash boiled in order to accelerate, eject, or propel one or more
frozen particles for delivery or administration to at least one
cell, tissue, or subject. In one embodiment, the flash boiling is
induced by one or more laser pulses (e.g., an infrared laser
pulse). In one embodiment, the one or more frozen particles are
prepared, delivered, or administered by another means.
[0799] In certain instances, it is desirable to deliver the one or
more frozen particle compositions, or frozen piercing implements to
at least one cell or tissue, or administer the one or more frozen
particle compositions, or frozen piercing implements to at least
one subject. In at least one instance, the one or more frozen
particle compositions, or frozen piercing implements include a
plurality of frozen particle compositions, or frozen piercing
implements that include two or more subsets of frozen particle
compositions, or frozen piercing implements that are delivered or
administered in sequential order. In one embodiment, the sequential
order is predetermined, based on factors relating to, for example,
the at least one cell or tissue, the at least one subject, or the
at least one frozen particle composition, or frozen piercing
implement. In one embodiment, the sequential order is determined,
for example, during the course of delivery or administration of at
least one of the one or more frozen particles or at least one
frozen particle composition, or frozen piercing implement. In one
embodiment, the sequential order is determined by a software
program. In one embodiment, the sequential order of delivery is
randomized.
[0800] In one embodiment, the sequential order includes one or more
subsets of frozen particle compositions, or frozen piercing
implements that vary in size, shape, weight, density, location of
delivery or administration, time of delivery or administration,
angle of delivery or administration, or velocity of delivery or
administration. In one embodiment, one or more subsets of frozen
particle compositions, or frozen piercing implements are delivered
or administered according to a course of treatment (e.g., at least
one subset of relatively small frozen particle compositions, or
frozen piercing implements are administered first, followed by at
least one subset of relatively larger frozen particle compositions,
or frozen piercing implements; at least one subset of frozen
particle compositions, or frozen piercing implements are
administered in a relatively fast velocity, followed by at least
one subset of frozen particle compositions, or frozen piercing
implements administered by a relatively slow velocity; at least one
subset of frozen particle compositions, or frozen piercing
implements approximately shaped as spheroids are administered
followed by at least one subset of frozen particle compositions, or
frozen piercing implements approximately shaped as bullets,
etc.).
[0801] In one embodiment, the at least one frozen particle
composition, or frozen piercing implement is propelled using a
pressure set at least about 1 psi, about 5 psi, about 10 psi, about
20 psi, about 30 psi, about 40 psi, about 50 psi, at least about
100 psi, at least about 200 psi, at least about 300 psi, at least
about 400 psi, at least about 450 psi, at least about 500 psi, at
least about 600 psi, at least about 700 psi, at least about 800
psi, at least about 900 psi, at least about 1000 psi, at least
about 1100 psi, at least about 1200 psi, at least about 1300 psi,
at least about 1400 psi, at least about 1500 psi, about 2000 psi,
about 2500 psi, about 3000 psi, about 3500 psi, about 4000 psi,
about 5000 psi, about 6000 psi, about 7000 psi, about 8000 psi,
about 9000 psi, about 10000 psi, about 20000 psi, about 30000 psi,
about 40000 psi, about 50000 psi, or any value therebetween.
[0802] In one embodiment, the at least one frozen particle
composition, or frozen piercing implement is propelled at a
pressure ranging from approximately 350 psi to approximately 1000
psi. In one embodiment, for example for penetrating the skin
(particularly epidermis or dermis), the at least one frozen
particle composition, or frozen piercing implement is propelled at
a pressure of approximately 800 psi to approximately 1000 psi. See,
for example, Menon et al., Skin Pharmacol. Physiol. vol. 20, pp.
141-147 (2007), which is incorporated herein by reference. For
example, microwounds caused by gold beads bombarding the skin did
not reseal with stratum corneum lipids after 24 hours of organ
culture. Id. In one embodiment, these microwounds allow for
increased permeability of the substrate for delivery of at least
one agent.
[0803] In one embodiment, the at least one frozen particle
composition, or frozen piercing implement is propelled to or at a
predetermined depth, predetermined velocity, predetermined rate of
administration, predetermined angle, predetermined spatial
location, predetermined depth, predetermined time sequence, or
predetermined spatial pattern for delivery of the at least one
composition to a desired location of the at least one biological
tissue. In one embodiment, the velocity, rate, or angle of
administration of the one or more frozen particle compositions, or
frozen piercing implements are variable. In one embodiment, a
method of administering one or more frozen particle compositions,
or frozen piercing implements includes varying the rate, velocity,
or angle. In one embodiment, a method includes multiple
administrations of the one or more frozen particle compositions, or
frozen piercing implements, wherein at least two of the
administrations include different velocities, rates, or angles of
delivery.
[0804] In one embodiment, the at least one frozen particle
composition; or frozen piercing implement is propelled to or at a
velocity of approximately 1 m/s, approximately 5 m/s, approximately
10 m/s, approximately 20 m/s, approximately 30 m/s, approximately
40 m/s, approximately 50 m/s, approximately 60 m/s, approximately
70 m/s, approximately 80 m/s, approximately 90 m/s, approximately
100 m/s, approximately 200 m/s, approximately 300 m/s,
approximately 400 m/s, approximately 500 m/s, approximately 600
m/s, approximately 700 m/s, approximately 800 m/s, approximately
900 m/s, approximately 1000 m/s, approximately 1500 m/s,
approximately 2000 m/s, approximately 3000 m/s, approximately 4000
m/s, approximately 5000 m/s, or any value greater or
therebetween.
[0805] In one embodiment, the at least one frozen particle
composition, or frozen piercing implement is accelerated or ejected
toward the at least one substrate (such as a biological tissue) to
a velocity of approximately 1 m/s, approximately 5 m/s,
approximately 10 m/s, approximately 20 m/s, approximately 30 m/s,
approximately 40 m/s, approximately 50 m/s, approximately 60 m/s,
approximately 70 m/s, approximately 80 m/s, approximately 90 m/s,
approximately 100 m/s, approximately 200 m/s, approximately 300
m/s, approximately 400 m/s, approximately 500 m/s, approximately
600 m/s, approximately 700 m/s, approximately 800 m/s,
approximately 900 m/s, approximately 1000 m/s, approximately 1500
m/s, approximately 2000 m/s, approximately 3000 m/s, approximately
4000 m/s, approximately 5000 m/s, or any value greater or
therebetween.
[0806] In one embodiment, delivering at least one frozen particle
composition, or frozen piercing implement to at least one substrate
(such as a biological tissue) includes accelerating, ejecting, or
propelling a plurality of frozen particle compositions, or frozen
piercing implements toward the at least one substrate (including a
biological tissue). In one embodiment, the plurality of frozen
particle compositions, or frozen piercing implements is
administered to at least one substrate including at a predetermined
angle, a predetermined velocity, a predetermined rate of
administration, a predetermined spatial pattern, a predetermined
spatial location, a predetermined time sequence, or a predetermined
depth. Such a plurality of particles may include one embodiment
wherein two or more frozen particle compositions, or frozen
piercing implements of the plurality include one or more similar
agents. Likewise, a plurality of frozen particle compositions, or
frozen piercing implements may include one embodiment wherein two
or more frozen particle compositions, or frozen piercing implements
include one or more dissimilar agents. In one embodiment, the rate,
velocity, or angle at which the one or more frozen particle
compositions, or frozen piercing implements are administered is
variable.
[0807] In one embodiment, a device for making and propelling one or
more frozen particle compositions, or frozen piercing implements
includes at least one particle accelerator. In one embodiment, the
particle accelerator includes a linear, circular or spherical
accelerator. In one embodiment, the particle accelerator includes a
spiral, conical, helical, or conic-helical accelerator. In one
embodiment, the particle accelerator includes a 2-dimensional or
3-dimensional accelerator.
[0808] For example, in a 2-dimensional spiral, polar coordinates
can be expressed as a function of angle .theta., where the radius r
is a continuous monotonic function of angle .theta., and a and b
are arbitrary positive real constants. For example, several
embodiments are shown in FIG. 135 A-K.
[0809] As described herein, a plurality of frozen particle
compositions, or frozen piercing implements may include one or more
subsets, which can be delivered or administered in an order of
operations. In one embodiment, the order of operations includes
delivery or administration in a pattern. In one embodiment, the
order of operations includes delivery or administration in a
predetermined pattern. In one embodiment, the order of operations
includes delivery or administration in sequential order. In one
embodiment, the order of operations includes delivery or
administration at random.
[0810] For embodiments described herein, those having skill in the
art will recognize that the state of the art has progressed to the
point where there is little distinction left between hardware,
software, and/or firmware implementations of aspects of systems;
the use of hardware, software, and/or firmware is generally (but
not always, in that in certain contexts the choice between hardware
and software can become significant) a design choice representing
cost vs. efficiency tradeoffs. Those having skill in the art will
appreciate that there are various vehicles by which processes
and/or systems and/or other technologies described herein can be
effected (e.g., hardware, software, and/or firmware), and that the
preferred vehicle will vary with the context in which the processes
and/or systems and/or other technologies are deployed. For example,
if an implementer determines that speed and accuracy are paramount,
the implementer may opt for a mainly hardware and/or firmware
vehicle; alternatively, if flexibility is paramount, the
implementer may opt for a mainly software implementation; or, yet
again alternatively, the implementer may opt for some combination
of hardware, software, and/or firmware. Hence, there are several
possible vehicles by which the processes and/or devices and/or
other technologies described herein can be effected, none of which
is inherently superior to the other in that any vehicle to be
utilized is a choice dependent upon the context in which the
vehicle will be deployed and the specific concerns (e.g., speed,
flexibility, or predictability) of the implementer, any of which
may vary. Those skilled in the art will recognize that optical
aspects of implementations will typically employ optically-oriented
hardware, software, and or firmware.
[0811] In some implementations described herein, logic and similar
implementations may include software or other control structures.
Electronic circuitry, for example, may have one or more paths of
electrical current constructed and arranged to implement various
functions as described herein. In some implementations, one or more
media can be configured to bear a device-detection implementation
when such media hold or transmit device detection instructions
operable to perform as described herein. In some variants, for
example, implementations may include an update or modification of
existing software or firmware, or of gate arrays or programmable
hardware, such as by performing a reception of or a transmission of
one or more instructions in relation to one or more operations
described herein. Alternatively or additionally, in some variants,
an implementation may include special-purpose hardware, software,
firmware components, and/or general-purpose components executing or
otherwise invoking special-purpose components. Specifications or
other implementations can be transmitted by one or more instances
of tangible transmission media as described herein, optionally by
packet transmission or otherwise by passing through distributed
media at various times.
[0812] Alternatively or additionally, implementations may include
executing a special-purpose instruction sequence or invoking
circuitry for enabling, triggering, coordinating, requesting, or
otherwise causing one or more occurrences of virtually any
functional operations described herein. In some variants,
operational or other logical descriptions herein can be expressed
as source code and compiled or otherwise invoked as an executable
instruction sequence. In some contexts, for example, C++ or other
code sequences can be compiled or implemented in high-level
descriptor languages (e.g., a logic-synthesizable language, a
hardware description language, a hardware design simulation, and/or
other such similar mode(s) of expression). For example, some or all
of the logical expression can be manifested as a Verilog-type
hardware description or other circuitry model before physical
implementation in hardware. Those skilled in the art will recognize
how to obtain, configure, and optimize suitable transmission or
computational elements, material supplies, actuators, or other
structures in light of these teachings.
[0813] As indicated in FIGS. 7-9, one embodiment, a method 700
includes comparing 710 information regarding at least one aspect of
administering at least one frozen particle composition (or frozen
piercing implement) to at least one subject and information
regarding at least one clinical outcome following receipt by the at
least one subject of at least one frozen particle composition (or
frozen piercing implement); and providing output information
optionally based on the comparison.
[0814] In one embodiment, the method includes determining at least
one statistical correlation 720. In one embodiment, the method
includes counting the occurrence of at least one clinical outcome
730. In one embodiment, the method includes determining at least
one correlation before the administration of the at least one
frozen particle composition (or frozen piercing implement) 735. In
one embodiment, information regarding at least one aspect of
administering at least one frozen particle composition (or frozen
piercing implement) includes information regarding the amount of at
least one frozen particle composition (or frozen piercing
implement) or therapeutic agent administered to at least one
biological tissue of a subject 740. In one embodiment, the
information regarding at least one aspect of administering or
delivering at least one frozen particle composition (or frozen
piercing implement) includes information regarding at least one
dimension of biological tissue penetration 750. In one embodiment,
information regarding the at least one dimension of biological
tissue penetration includes information regarding at least one of
depth, width, or breadth of administration of at least one frozen
particle composition (or frozen piercing implement) to at least one
biological tissue of at least one subject 760.
[0815] In one embodiment, the information regarding at least one
aspect of administering at least one frozen particle composition
(or frozen piercing implement) includes information regarding two
or more subjects with one or more common attributes 770. In one
embodiment, the one or more common attributes include genetic
attributes, mental attributes, or psychological attributes 780. In
at least on embodiment, the one or more common attributes include
genotype attributes or phenotype attributes 790.
[0816] In one embodiment, the one or more common attributes 797
include at least one of height; weight; medical diagnosis; familial
background; results on one or more medical tests; ethnic
background; body mass index; age; presence or absence of at least
one disease or condition; species; ethnicity; race; allergies;
gender; thickness of epidermis; thickness of dermis; thickness of
stratum corneum; keratin deposition; collagen deposition; blood
vessel condition; skin condition; hair or fur condition; muscle
condition; tissue condition; organ condition; nerve condition;
brain condition; presence or absence of at least one biological,
chemical, or therapeutic agent in the subject; pregnancy status;
lactation status; genetic profile; proteomic profile; lipidomic
profile, glycomic profile, system biology profile, partial or whole
genetic sequence; partial or whole proteomic sequence; medical
history; lymph condition, circulatory condition, respiratory
condition, or blood condition.
[0817] In one embodiment, the output information 810 includes at
least one of a response signal, a comparison code, a comparison
plot, a diagnostic code, a treatment code, a test code, a code
indicative of at least one treatment received, a code indicative of
at least one prescribed treatment step, a code indicative of at
least one vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of an
administered or delivered frozen particle composition (or frozen
piercing implement). In one embodiment, the at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding at least one cellular or tissue source 820. In one
embodiment, the information regarding at least one tissue source
includes information regarding at least one abnormal cellular or
tissue source 830. In one embodiment, the information regarding at
least one cellular or tissue source includes information regarding
at least one type of cell or tissue 840. In one embodiment, the
cellular or tissue source includes at least one cell or biological
tissue described herein.
[0818] In one embodiment, the at least one frozen particle
composition, frozen piercing implement, frozen piercing implement
device, or therapeutic composition includes at least one of
nitrogen, carbon dioxide, hydrogen oxide, helium, neon, xenon,
krypton, chlorine, bromine, methane, oxygen, air, argon,
polyethylene glycol, acetone, ethyl acetate, dimethyl sulfoxide,
dimethyl formamide, dioxane, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, acetic acid, benzene, carbon
tetrachloride, hexane, methylene chloride, carboxylic acid, saline,
Ringer's solution, lactated Ringer's solution, Hartmann's solution,
acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether 850.
[0819] In one embodiment, the at least one frozen particle
composition, frozen piercing implement, frozen piercing implement
device, or therapeutic composition includes at least one major
dimension of approximately one decimeter or less, or approximately
one centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer
or less, or any value therebetween 860.
[0820] In one embodiment, the at least one frozen particle
composition, frozen piercing implement, frozen piercing implement
device, or therapeutic composition includes one or more
reinforcement agents 870. In one embodiment, the at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition includes one or more explosive materials
880. In one embodiment, the receipt by the at least one subject of
at least one frozen particle composition (or frozen piercing
implement) or therapeutic composition is pursuant to at least one
clinical trial 900.
[0821] In one embodiment, the method includes creating at least one
inclusion criterion and at least one exclusion criterion for a
clinical trial involving the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition 910. In one embodiment, the method further comprises
suggesting the inclusion of one or more of the at least one subject
in at least one clinical trial 920. In one embodiment, the method
further comprises suggesting the exclusion of one or more of the at
least one subject in at least one clinical trial 930. In certain
instances, multiple subjects from multiple clinical trials are
included. In one embodiment, the method further includes using one
or more of the at least one comparison to predict at least one
clinical outcome regarding at least one second subject 940. In one
embodiment, the at least one second subject has not received the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition 950. In one embodiment, the
at least one second subject is a plurality of people; and the
method further comprises segregating subject identifiers associated
with the plurality of people in reference to the predicted at least
one clinical outcome 960. In one embodiment, the at least one
second subject is a plurality of people; and the method further
comprises determining the eligibility of the at least one second
subject for the at least one clinical trial 970.
[0822] As indicated in FIGS. 10-12, at least one aspect includes a
method 1000 relating to predicting a clinical outcome of
administering at least one frozen particle therapeutic composition
(or frozen piercing implement) to at least one biological tissue of
at least one first subject includes determining a similarity or a
dissimilarity in information regarding at least one aspect of
administering at least one therapeutic composition (or frozen
piercing implement) to the at least one biological tissue of the at
least one first subject to information regarding at least one
aspect of administering at least one therapeutic composition (or
frozen piercing implement) to the at least one biological tissue of
the at least one second subject, wherein the at least one second
subject attained a clinical outcome following receipt of the at
least one frozen particle therapeutic composition(or frozen
piercing implement); and providing output information optionally
based on the determination 1010.
[0823] In one embodiment, the information regarding the at least
one aspect of administering at least one frozen particle
therapeutic composition (or frozen piercing implement) includes
information 1020 regarding the amount of at least one frozen
particle therapeutic composition (or frozen piercing implement) or
therapeutic agent delivered to at least one biological tissue of a
subject. In one embodiment, the information regarding the at least
one aspect of administering at least one frozen particle
therapeutic composition (or frozen piercing implement) includes
information 1030 regarding at least one dimension of biological
tissue penetration. In one embodiment, the information regarding
the at least one dimension of biological tissue penetration
includes information 1040 regarding at least one of depth, width,
or breadth of delivery of at least one frozen particle therapeutic
composition (or frozen piercing implement) to at least one
biological tissue of at least one subject; or information 1050
regarding two or more subjects with common attributes.
[0824] In one embodiment, the one or more common attributes include
genetic attributes, mental attributes, or psychological attributes
1060. In at least on embodiment, the one or more common attributes
include genotype attributes or phenotype attributes 1070.
[0825] In one embodiment, the one or more common attributes 1080
include at least one of height; weight; medical diagnosis; familial
background; results on one or more medical tests; ethnic
background; body mass index; age; presence or absence of at least
one disease or condition; species; ethnicity; race; allergies;
gender; thickness of epidermis; thickness of dermis; thickness of
stratum corneum; keratin deposition; collagen deposition; blood
vessel condition; skin condition; hair or fur condition; muscle
condition; tissue condition; organ condition; nerve condition;
brain condition; presence or absence of at least one biological,
chemical, or therapeutic agent in the subject; pregnancy status;
lactation status; genetic profile; proteomic profile; partial or
whole genetic sequence; medical history; partial or whole proteomic
sequence; lymph condition, or blood condition.
[0826] In one embodiment, the output information 1100 includes at
least one of a response signal, a comparison code, a comparison
plot, a diagnostic code, a treatment code, a test code, a code
indicative of at least one treatment received, a code indicative of
at least one prescribed treatment step, a code indicative of at
least one vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of an
administered or delivered frozen particle composition (or frozen
piercing implement) or therapeutic composition. In one embodiment,
the at least one aspect of cellular or tissue abrasion or ablation
includes information regarding at least one cellular or tissue
source 1110. In one embodiment, the information regarding at least
one tissue source includes information regarding at least one
abnormal cellular or tissue source 1120. In one embodiment, the
information regarding at least one cellular or tissue source
includes information regarding at least one type of cell or tissue
1130. In one embodiment, the cellular or tissue source includes at
least one cell or biological tissue described herein.
[0827] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) includes at least one of
nitrogen, carbon dioxide, hydrogen oxide, helium, neon, xenon,
krypton, chlorine, bromine, methane, oxygen, air, argon,
polyethylene glycol, acetone, ethyl acetate, dimethyl sulfoxide,
dimethyl formamide, dioxane, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, acetic acid, benzene, carbon
tetrachloride, hexane, methylene chloride, carboxylic acid, saline,
Ringer's solution, lactated Ringer's solution, Hartmann's solution,
acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether
1140.
[0828] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes at least one major dimension of approximately
one decimeter or less, or approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer or less, or any value
therebetween 1150.
[0829] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes one or more reinforcement agents 1160. In one
embodiment, the at least one frozen particle composition (or frozen
piercing implement) or therapeutic composition includes one or more
explosive materials 1170.
[0830] In one embodiment, the receipt by the at least one subject
of at least one frozen particle composition (or frozen piercing
implement) or therapeutic composition is pursuant to at least one
clinical trial 1200. In one embodiment, the method further
comprises determining at least one correlation before the
administration or delivery of the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition to at least one subject 1210. The at least one subject
includes, but is not limited to at least one subject described
herein.
[0831] In one embodiment, the method includes creating at least one
inclusion criterion and at least one exclusion criterion for a
clinical trial involving the at least one frozen particle
composition or therapeutic composition 1220. In one embodiment, the
method further comprises suggesting the inclusion of one or more of
the at least one subject in at least one clinical trial 1230. In
one embodiment, the method further comprises suggesting the
exclusion of one or more of the at least one subject in at least
one clinical trial 1240. In certain instances, multiple subjects
from multiple clinical trials are included. In one embodiment, the
method further includes using one or more of the at least one
comparison to predict at least one clinical outcome regarding at
least one second subject 1250. In one embodiment, the at least one
second subject has not received the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition 1260. In one embodiment, the method includes predicting
at least one clinical outcome involving the at least one second
subject, and the at least one second subject is a plurality of
people; and the method further comprises segregating subject
identifiers associated with the plurality of people in reference to
the predicted at least one clinical outcome 1270.
[0832] In one embodiment, the at least one second subject is a
plurality of people; and the method further comprises determining
the eligibility of the at least one second subject for the at least
one clinical trial 1280.
[0833] As shown in FIGS. 13-15, one embodiment includes a system
1300 including at least one computer program 1310, configured with
a computer-readable medium, for use with at least one computer
system and wherein the computer program includes a plurality of
instructions including but not limited to one or more instructions
1320 for comparing information regarding at least one aspect of at
least one therapeutic administration of at least one frozen
particle composition (or frozen piercing implement) or therapeutic
composition to at least one subject. In one embodiment, information
1330 regarding amount of the at least one frozen particle
composition, (or frozen piercing implement), therapeutic
composition, or therapeutic agent administered to at least one
biological tissue of at least one subject. In one embodiment,
information regarding at least one aspect of at least one
therapeutic administration of at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes information regarding at least one dimension
of biological tissue penetration 1340. In one embodiment,
information regarding at least one aspect of at least one
therapeutic administration of at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes information regarding at least one of depth,
width, or breadth of administration of at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition to at least one biological tissue of at least one
subject 1350. In one embodiment, information regarding at least one
aspect of at least one therapeutic administration includes
information regarding two or more subjects with one or more common
attributes 1360. In one embodiment, the computing device is
configured to communicate with at least one imaging device. In one
embodiment, the computing device is configured to communicate with
at least one printing device. In one embodiment, the computing
device is configured to communicate with at least one input device
1370.
[0834] In one embodiment, the information regarding at least one
aspect of therapeutic administration of at least one therapeutic
composition includes information regarding at least one cellular or
tissue source 1400; information regarding at least one abnormal
cellular or tissue source 1410; or information regarding at least
one type of cell or tissue 1420. In one embodiment, at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition includes at least one of nitrogen, carbon
dioxide, hydrogen oxide, helium, neon, xenon, krypton, chlorine,
bromine, methane, oxygen, air or argon. In one embodiment, the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition includes at least one of
polyethylene glycol, acetone, ethyl acetate, dimethyl sulfoxide,
dimethyl formamide, dioxane, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, acetic acid, benzene, carbon
tetrachloride, hexane, methylene chloride, carboxylic acid, saline,
Ringer's solution, lactated Ringer's solution, Hartmann's solution,
acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether 1430. In
one embodiment, at least one frozen particle composition (or frozen
piercing implement) or therapeutic composition includes at least
one major dimension of approximately one decimeter or less,
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer or less, or any value therebetween 1440. In one
embodiment, the at least one frozen particle composition (or frozen
piercing implement) or therapeutic composition includes one or more
reinforcement agents 1450 or one or more explosive materials
1460.
[0835] In one embodiment, the receipt by the at least one subject
of at least one frozen particle composition (or frozen piercing
implement) or therapeutic composition is pursuant to at least one
clinical trial 1500. In one embodiment, the system further
comprises determining at least one correlation before the delivery
or administration of the at least one frozen particle composition
(or frozen piercing implement) or therapeutic composition to at
least one subject 1510.
[0836] In one embodiment, the method includes creating at least one
inclusion criterion and at least one exclusion criterion for a
clinical trial involving the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition 1520. In one embodiment, the instructions further
comprise suggesting the inclusion of one or more of the at least
one subject in at least one clinical trial 1530. In certain
instances, multiple subjects from multiple clinical trials are
included.
[0837] In one embodiment, the instructions include suggesting the
exclusion of one or more of the at least one subject in at least
one clinical trial 1540.
[0838] In one embodiment, a method includes using one or more of
the at least one comparison to predict at least one clinical
outcome regarding at least one second subject 1550. In one
embodiment, the at least one second subject has not received the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition 1560. In one embodiment, the
at least one second subject is a plurality of people; and further
comprising segregating subject identifiers associated with the
plurality of people in reference to the predicted at least one
clinical outcome 1570.
[0839] In one embodiment, the using one or more of the at least one
comparison, wherein the at least one second subject is a plurality
of people; and further comprising determining the eligibility of
the at least one second subject for the at least one clinical trial
1580.
[0840] As indicated in FIG. 16, one embodiment relates to a system
1600 including at least one computer program 1610 configured with a
computer-readable medium, for use with at least one computer system
and wherein the computer program includes a plurality of
instructions including but not limited to one or more instructions
1620 for comparing information regarding at least one aspect of at
least one therapeutic administration of at least one frozen
particle therapeutic composition (or frozen piercing implement) to
at last one subject, and information regarding at least one frozen
particle therapeutic composition (or frozen piercing implement)
involving at least one biological tissue of at least one subject;
and one or more instructions for applying one or more comparisons
to the information regarding the at least one aspect of therapeutic
administration of at least one frozen particle therapeutic
composition (or frozen piercing implement) to a plurality of
people. In one embodiment, the computer program includes one or
more instructions 1630 for segregating subject identifiers
associated with the plurality of people in reference to at least
one of the one or more applied comparisons. In one embodiment,
information regarding at least one aspect of at least one
therapeutic administration includes information 1640 regarding the
amount of at least one frozen particle composition (or frozen
piercing implement), therapeutic composition or therapeutic agent
administered to at least one biological tissue of at least one
subject; information 1650 regarding at least one dimension of
biological tissue penetration; information 1660 regarding at least
one of depth, width, or breadth of administration of at least one
frozen particle therapeutic composition to at least one biological
tissue of at least one subject. In one embodiment, the computer
program includes one or more instructions 1670 for segregating
individual identifiers associated with the plurality of people in
reference to at least one characteristic shared by two or more
subjects in the plurality of people.
[0841] As shown in FIG. 17, one embodiment relates to a computer
program product 1700 that includes a signal bearing medium 1710
bearing at least one of one or more instructions 1720 for receiving
a first input associated with a first possible dataset, the first
possible dataset including data representative of one or more
measurements relating to one or more physical attributes of a first
subject; one or more instructions 1730 for comparing a value
associated with the first possible dataset with a second dataset
including values representative of predictive regimen parameters
from a second subject with one or more similar or dissimilar
physical attributes; one or more instructions 1740 for determining
from the comparison at least one frozen particle therapeutic
composition (or frozen piercing implement) regimen for the first
subject and output information; one or more instructions 1750 for
accessing the first possible dataset in response to the first
input; one or more instructions 1760 for generating the first
possible dataset in response to the first input; one or more
instructions 1770 for determining a graphical illustration of the
first possible dataset; one or more instructions 1780 for
determining a graphical illustration of the second possible
dataset; and at least one generated output optionally based on the
determination.
[0842] In one embodiment, the computer program product includes a
signal bearing medium that includes a computer-readable medium
1790. In one embodiment, the signal bearing medium of the computer
program product includes a recordable medium 1792.
[0843] In one embodiment, the computer program product includes a
signal bearing medium that includes a communications medium
1794.
[0844] As indicated in FIG. 18, one embodiment relates to a
computer program product 1800 that includes a signal bearing medium
1810 bearing at least one of one or more instructions 1820 for
processing a first possible dataset, the first possible dataset
including data representative of one or more measurements relating
to one or more physical attributes of a first subject; one or more
instructions 1830 for comparing a value associated with the first
possible dataset with a second dataset including values
representative of predictive regimen parameters from a second
subject with one or more similar or dissimilar physical attributes;
one or more instructions 1840 for determining from the comparison
at least one frozen particle composition (or frozen piercing
implement) or therapeutic composition treatment regimen for the
first subject, and output information.
[0845] As indicated in FIG. 19, one embodiment relates to a
computer program product 1900 that includes a signal bearing medium
1910 bearing at least one of one or more instructions 1920
responsive to a first possible dataset, the first possible dataset
including data representative of one or more measurements relating
to one or more physical attributes of a first subject; one or more
instructions 1930 for comparing a value associated with the first
possible dataset with a second dataset including values
representative of predictive regimen parameters for a second
subject with one or more similar or dissimilar physical attributes;
one or more instructions 1940 for determining from the comparison
at least one frozen particle composition (or frozen piercing
implement) or therapeutic composition treatment regimen for the
first subject; and output information optionally based on the
determination.
[0846] As shown in FIG. 20, one embodiment relates to a computer
program product 2000 that includes a signal bearing medium 2010
bearing at least one of one or more instructions 2020 for receiving
a first input associated with a first possible dataset, the first
possible dataset including data representative of one or more
measurements relating to one or more physical attributes of a
subject; one or more instructions 2030 for comparing a value
associated with the first possible dataset with a second dataset
including values representative of parameters relating to one or
more expected biological changes following administration of one or
more frozen particle compositions (or frozen piercing implements)
or therapeutic compositions; one or more instructions 2040 for
determining from the comparison at least one biological change
following administration of one or more frozen particle
compositions (or frozen piercing implements) or therapeutic
compositions to the subject; at least one generated output
optionally based on the determination.
[0847] In one embodiment, the computer program product includes one
or more instructions 2050 for accessing the first possible dataset
in response to the first input. In one embodiment, the computer
program product includes one or more instructions 2060 for
generating the first possible dataset in response to the first
input.
[0848] In one embodiment, the computer program product includes one
or more instructions 2070 for determining a graphical illustration
of the first possible dataset. In one embodiment, the computer
program product includes one or more instructions 2080 for
determining a graphical illustration of the second possible
dataset. In one embodiment, the signal bearing medium includes a
computer-readable medium 2090. In one embodiment, the signal
bearing medium includes a recordable medium 2092. In one
embodiment, the signal bearing medium includes a communications
medium 2094.
[0849] As indicated in FIG. 21, one embodiment a computer program
product 2100 includes a signal bearing medium 2110 bearing at least
one of one or more instructions 2120 for processing a first input
associated with a first possible dataset, the first possible
dataset including data representative of one or more measurements
relating to one or more physical attributes of a subject; one or
more instructions 2130 for comparing a value associated with the
first possible dataset with a second dataset including values
representative of parameters relating to one or more expected
biological changes following administration of one or more frozen
particle compositions (or frozen piercing implements) or
therapeutic compositions; one or more instructions 2140 for
determining from the comparison at least one biological change
following administration of one or more frozen particle
compositions (or frozen piercing implements) or therapeutic
compositions to the subject; at least one generated output
optionally based on the determination.
[0850] As shown in FIG. 22, one embodiment relates to a computer
program product 2200 includes a signal bearing medium 2210 bearing
at least one of one or more instructions 2220 responsive to a first
possible dataset, the first possible dataset including data
representative of one or more measurements relating to one or more
physical attributes of a subject; one or more instructions 2230 for
comparing a value associated with the first possible dataset with a
second dataset including values representative of parameters
relating to one or more expected biological changes following
administration of one or more frozen particle compositions (or
frozen piercing implements) or therapeutic compositions; one or
more instructions 2240 for determining from the comparison at least
one biological change following administration of one or more
frozen particle compositions (or frozen piercing implements) or
therapeutic compositions to the subject; and output information
optionally based on the determination.
[0851] As indicated in FIGS. 23-25, one embodiment, a method 2300
includes comparing 2310 information regarding at least one aspect
of cellular or tissue abrasion or ablation of at least one
biological tissue of at least one subject and information regarding
at least one clinical outcome following receipt by the at least one
subject of at least one frozen particle composition (or frozen
piercing implement) or therapeutic composition; and providing
output information optionally based on the determination. In one
embodiment, the method includes determining at least one
statistical correlation 2320. In one embodiment, the method
includes counting the occurrence of at least one clinical outcome
2330. In one embodiment, the information regarding at least one
aspect of cellular or tissue abrasion or ablation includes
information regarding quantity of cells or tissue removed or
destroyed 2340. In one embodiment, the information regarding at
least one aspect of cellular or tissue abrasion or ablation
includes information regarding at least one dimension of cellular
or tissue removal or destruction, or removal or destruction of
other materials, such as plaque, extracellular matrix, collagen,
elastin, protein, or other materials 2350. In one embodiment,
information regarding the at least one dimension of cellular
removal or destruction includes information regarding at least one
of depth, width, or breadth of cellular removal or destruction
2360.
[0852] In one embodiment, the information regarding at least one
aspect of cellular or tissue abrasion or ablation includes
information regarding two or more subjects with one or more common
attributes 2370. In one embodiment, the one or more common
attributes include genetic attributes, mental attributes, or
psychological attributes 2380. In at least on embodiment, the one
or more common attributes include genotype attributes or phenotype
attributes 2390.
[0853] In one embodiment, the one or more common attributes 2397
include at least one of height; weight; medical diagnosis; familial
background; results on one or more medical tests; ethnic
background; body mass index; age; presence or absence of at least
one disease or condition; species; ethnicity; race; allergies;
gender; thickness of epidermis; thickness of dermis; thickness of
stratum corneum; keratin deposition; collagen deposition; blood
vessel condition; skin condition; hair or fur condition; muscle
condition; tissue condition; organ condition; nerve condition;
brain condition; presence or absence of at least one biological,
chemical, or therapeutic agent in the subject; pregnancy status;
lactation status; genetic profile; proteomic profile; partial or
whole genetic sequence; medical history; partial or whole proteomic
sequence; lymph condition, or blood condition.
[0854] In one embodiment, the output information 2410 includes at
least one of a response signal, a comparison code, a comparison
plot, a diagnostic code, a treatment code, a test code, a code
indicative of at least one treatment received, a code indicative of
at least one prescribed treatment step, a code indicative of at
least one vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of a
delivered or administered frozen particle composition (or frozen
piercing implement). In one embodiment, the at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding at least one cellular or tissue source 2420. In one
embodiment, the information regarding at least one tissue source
includes information regarding at least one abnormal cellular or
tissue source 2430. In one embodiment, the information regarding at
least one cellular or tissue source includes information regarding
at least one type of cell or tissue 2440. In one embodiment, the
cellular or tissue source includes at least one cell or biological
tissue described herein.
[0855] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes at least one of nitrogen, carbon dioxide,
hydrogen oxide, helium, neon, xenon, krypton, chlorine, bromine,
methane, oxygen, air, argon, polyethylene glycol, acetone, ethyl
acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, acetic acid, benzene, carbon tetrachloride, hexane,
methylene chloride, carboxylic acid, saline, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether 2450.
[0856] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) includes at least one
major dimension of approximately one decimeter or less, or
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer or less, or any value therebetween 2460.
[0857] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) includes one or more
reinforcement agents 2470. In one embodiment, the at least one
frozen particle composition (or frozen piercing implement) includes
one or more explosive materials 2480. In one embodiment, the
receipt by the at least one subject of at least one frozen particle
composition (or frozen piercing implement) is pursuant to at least
one clinical trial 2500. In one embodiment, the method further
comprises determining at least one correlation 2510 before the
delivery or administration of the at least one frozen particle
composition (or frozen piercing implement) to at least one subject.
The at least one subject includes, but is not limited to at least
one subject described herein.
[0858] In one embodiment, the method includes creating at least one
inclusion criterion and at least one exclusion criterion for a
clinical trial involving the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition 2515. In one embodiment, the method further comprises
suggesting the inclusion of one or more of the at least one subject
in at least one clinical trial 2520. In one embodiment, the method
further comprises suggesting the exclusion of one or more of the at
least one subject in at least one clinical trial 2530. In certain
instances, multiple subjects from multiple clinical trials are
included. In one embodiment, the method further includes using one
or more of the at least one correlation to predict at least one
clinical outcome regarding at least one second subject 2540. In one
embodiment, the at least one second subject has not received the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition 2550. In one embodiment, the
method further comprises predicting at least one clinical outcome
involving the at least one second subject, wherein the at least one
second subject is a plurality of people; and segregating subject
identifiers associated with the plurality of people in reference to
the predicted at least one clinical outcome 2560. In one
embodiment, the at least one second subject is a plurality of
people; and the method further comprises determining the
eligibility of the at least one second subject for the at least one
clinical trial 2570.
[0859] As indicated in FIGS. 26-28, one embodiment relates to a
method 2600 of predicting a clinical outcome of at least one frozen
particle composition (or frozen piercing implement) treatment for
at least one first subject includes determining 2610 a similarity
or a dissimilarity in information regarding at least one aspect of
cellular or tissue abrasion or ablation of at least one biological
tissue of at least one first subject to information regarding at
least one aspect of cellular or tissue abrasion or ablation of at
least one biological tissue of at least one second subject, wherein
the at least one second subject attained a clinical outcome
following receipt of the at least one frozen particle composition
or therapeutic composition; and providing output information
optionally based on the determination.
[0860] In one embodiment, the information regarding at least one
aspect of cellular or tissue abrasion or ablation includes
information regarding the quantity of cells or tissue removed or
destroyed 2620. In one embodiment, the information regarding at
least one aspect of cellular or tissue abrasion or ablation
includes information regarding at least one dimension of cellular,
tissue, or other material removal or destruction 2630. In one
embodiment, the at least one dimension of cellular removal or
destruction includes information regarding at least one of depth,
width, or breadth of cellular removal or destruction 2640. In one
embodiment, the information regarding at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding two or more subjects with one or more common attributes
2650.
[0861] In one embodiment, the one or more common attributes include
but are not limited to genetic attributes, mental attributes, or
psychological attributes 2660. In one embodiment, the one or more
common attributes include genotype attributes or phenotype
attributes 2670.
[0862] In one embodiment, the one or more common attributes include
at least one of height; weight; medical diagnosis; familial
background; results on one or more medical tests; ethnic
background; body mass index; age; presence or absence of at least
one disease or condition; species; ethnicity; race; allergies;
gender; thickness of epidermis; thickness of dermis; thickness of
stratum corneum; keratin deposition; collagen deposition; blood
vessel condition; skin condition; hair or fur condition; muscle
condition; tissue condition; organ condition; nerve condition;
brain condition; presence or absence of at least one biological,
chemical, or therapeutic agent in the subject; pregnancy status;
lactation status; medical history; genetic profile; proteomic
profile; partial or whole genetic sequence; partial or whole
proteomic sequence; lymph condition, medical history, or blood
condition 2680.
[0863] In one embodiment, the output information includes at least
one of a response signal, a comparison code, a comparison plot, a
diagnostic code, a treatment code, a test code, a code indicative
of at least one treatment received, a code indicative of at least
one prescribed treatment step, a code indicative of at least one
vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of a
delivered or administered frozen particle composition (or frozen
piercing implement) 2700.
[0864] In one embodiment, the information regarding at least one
aspect of cellular or tissue abrasion or ablation includes
information regarding at least one cellular or tissue source 2710.
In one embodiment, the cellular or tissue source includes but is
not limited to at least one biological tissue or cell described
herein. In one embodiment, the information regarding at least one
tissue source includes information regarding at least one abnormal
cellular or tissue source 2720. In one embodiment, the information
regarding at least one cellular or tissue source includes
information regarding at least one type of cell or tissue 2730. In
one embodiment, the information regarding at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding at least one type of cell or tissue.
[0865] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes at least one of nitrogen, carbon dioxide,
hydrogen oxide, helium, neon, xenon, krypton, chlorine, bromine,
methane, oxygen, air or argon. In one embodiment, the at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition includes at least one of polyethylene
glycol, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl
formamide, dioxane, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, acetic acid, benzene, carbon
tetrachloride, hexane, methylene chloride, carboxylic acid, saline,
Ringer's solution, lactated Ringer's solution, Hartmann's solution,
acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether
2740.
[0866] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes at least one major dimension of approximately
one decimeter or less, or approximately one centimeter or less, or
approximately one millimeter or less, or approximately one
micrometer or less, or approximately one nanometer or less, or any
value therebetween 2750.
[0867] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes one or more reinforcement agents 2760. In one
embodiment, the at least one frozen particle composition (or frozen
piercing implement) or therapeutic composition includes one or more
explosive materials 2770.
[0868] In one embodiment, the receipt by the at least one subject
of at least one frozen particle composition (or frozen piercing
implement) or therapeutic composition is pursuant to at least one
clinical trial 2800. In one embodiment, the method includes
creating at least one inclusion criterion and at least one
exclusion criterion for a clinical trial involving the at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition 2810. In one embodiment, the method further
comprises suggesting the inclusion of one or more of the at least
one subject in at least one clinical trial 2820. In certain
instances, multiple subjects from multiple clinical trials are
included. In one embodiment, the method includes suggesting the
exclusion of one or more of the at least one subject in at least
one clinical trial 2830.
[0869] In one embodiment, a method includes using one or more of
the at least one determination to predict at least one clinical
outcome regarding at least one second subject 2840. In one
embodiment, the at least one second subject has not received the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition 2850. In one embodiment, the
at least one second subject is a plurality of people; and the
method further comprises segregating subject identifiers associated
with the plurality of people in reference to the predicted at least
one clinical outcome 2860.
[0870] In one embodiment, the using one or more of the at least one
comparison, wherein the at least one second subject is a plurality
of people; and the method further comprises determining the
eligibility of the at least one second subject for the at least one
clinical trial 2870.
[0871] As indicated in FIGS. 29-30, at least one aspect relates to
a system 2900 that includes at least one computing device 2910; one
or more instructions 2920 that when executed on the at least one
computing device cause the at least one computing device to receive
a first input associated with a first possible dataset, the first
possible dataset including data representative of one or more
measurements relating to one or more physical attributes of a first
subject; one or more instructions 2930 that when executed on the at
least one computing device cause the at least one computing device
to compare a value associated with the first possible dataset with
a second dataset including values representative of predictive
regimen parameters related to a second subject with one or more
similar or dissimilar physical attributes; one or more instructions
2940 that when executed on the at least one computing device cause
the at least one computing device to determine from the comparison
at least one frozen particle composition (or frozen piercing
implement) treatment regimen for the first subject; and at least
one generated output optionally based on the determination; one or
more instructions 2950 that when executed on the at least one
computing device cause the at least one computing device to access
the first possible dataset in response to the first input; one or
more instructions 2960 that when executed on the at least one
computing device cause the at least one computing device to
generate the first possible dataset in response to the first input;
one or more instructions 2970 that when executed on the at least
one computing device cause the at least one computing device to
determine a graphical illustration of the possible dataset; or one
or more instructions 3000 that when executed on the at least one
computing device cause the at least one computing device to
determine a graphical illustration of the second possible dataset.
In one embodiment, the treatment regimen includes at least one of
cellular or tissue removal, cellular or tissue ablation,
debridement, delivery of at least one therapeutic agent, cleaning
one or more wounds, oxygenating wounds, removing material from at
least one biological tissue, or removing material from at least one
blood vessel 3005. In at least one nitrogen, carbon dioxide,
hydrogen oxide, helium, neon, xenon, krypton, chlorine, bromine,
methane, oxygen, air, argon, polyethylene glycol, acetone, ethyl
acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, acetic acid, benzene, carbon tetrachloride, hexane,
methylene chloride, carboxylic acid, saline, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether 3008.
[0872] In one embodiment, the at least one computing device
includes one or more desktop computer, workstation computer,
computing system including a cluster of processors, a networked
computer, a tablet personal computer, a laptop computer, a mobile
device, a mobile telephone, or a personal digital assistant
computer 3010. In one embodiment, the at least one computing device
is configured to communicate with a database to access the first
possible dataset 3020. In one embodiment, the at least one
computing device is configured to communicate with a frozen
particle composition (or frozen piercing implement) selecting
apparatus, a frozen particle composition (or frozen piercing
implement) generating apparatus, or both 3030.
[0873] As shown in FIGS. 31-32, at least one aspect relates to a
system 3100 including circuitry 3110 for receiving a first input
associated with a first possible dataset, the first possible
dataset including data representative of one or more measurements
relating to one or more physical attributes of a first subject;
circuitry 3120 for comparing a value associated with the first
possible dataset with a second dataset including values
representative of predictive regimen parameters related to a second
subject with one or more similar or dissimilar physical attributes;
circuitry 3125 for determining from the comparison at least one
frozen particle composition (or frozen piercing implement)
treatment regimen for the first subject; circuitry 3128 for
selecting at least one of quality or quantity related to one or
more frozen particle compositions (or frozen piercing implements),
method of administration of one or more frozen particle
compositions (or frozen piercing implements), administration
location of one or more frozen particle compositions (or frozen
piercing implements), content of one or more frozen particle
compositions (or frozen piercing implements), timing of
administration of one or more frozen particle compositions (or
frozen piercing implements), decrease in physical dimension of one
or more frozen particle compositions (or frozen piercing
implements) or time interval between at least two deliveries with
one or more frozen particle compositions (or frozen piercing
implements).
[0874] In one embodiment, the system includes circuitry 3130 for
determining from the comparison at least one frozen particle
composition (or frozen piercing implement) treatment regimen for
the first subject; and circuitry 3140 for providing output
information optionally based on the comparison. In one embodiment,
the circuitry for receiving a first input associated with a first
possible dataset includes circuitry 3200 for receiving one or more
measurements relating to one or more physical attributes including
at least one of height; weight; body mass index; age; presence or
absence of at least one disease or condition; species; ethnicity;
race; allergies; gender; thickness of epidermis; thickness of
dermis; thickness of stratum corneum; keratin deposition; collagen
deposition; blood vessel condition; skin condition; hair or fur
condition; muscle condition; tissue condition; organ condition;
nerve condition; brain condition; presence or absence of at least
one biological, chemical, or therapeutic agent in the subject;
pregnancy status; lactation status; genetic profile; medical
history; proteomic profile; partial or whole genetic sequence;
partial or whole proteomic sequence; medical history; lymph
condition, or blood condition.
[0875] In one embodiment, the system includes circuitry 3210 for
selecting the combination of at least two parameters selected from
quality or quantity related to one or more frozen particle
compositions (or frozen piercing implements), method of
administration of one or more frozen particle compositions (or
frozen piercing implements), administration location of one or more
frozen particle compositions (or frozen piercing implements),
content of one or more frozen particle compositions (or frozen
piercing implements), timing of administration of one or more
frozen particle compositions (or frozen piercing implements),
decrease in a physical dimension of one or more frozen particle
compositions (or frozen piercing implements), or time interval
between at least two administrations or deliveries with one or more
frozen particle compositions (or frozen piercing implements).
[0876] In one embodiment, the system includes circuitry 3220 for
selecting the combination of at least two parameters selected from
quality or quantity related to one or more frozen particle
compositions (or frozen piercing implements), method of
administration of one or more frozen particle compositions (or
frozen piercing implements), administration location of one or more
frozen particle compositions (or frozen piercing implements),
content of one or more frozen particle compositions (or frozen
piercing implements), timing of administration of one or more
frozen particle compositions (or frozen piercing implements),
decrease in a physical dimension of one or more frozen particle
compositions (or frozen piercing implements), or time interval
between at least two administrations with one or more frozen
particle compositions (or frozen piercing implements).
[0877] In one embodiment, the system includes circuitry 3230 for
selecting at least one of a clinical outcome; secondary effects
related to the treatment; disease stage; longevity; or vaccination
administration. In one embodiment, the clinical outcome 3240
includes a positive clinical outcome or a negative clinical
outcome. In one embodiment, the clinical outcome includes one or
more adverse effect, failure to attain a clinical endpoint of a
clinical trial, failing to attain a beneficial effect, or
measurement of at least one biochemical, biological or
physiological parameter 3250.
[0878] FIGS. 33-35 illustrate a partial view of a system 3300
including at least one computer program 3310 configured with a
computer-readable medium, for use with at least one computer system
and wherein the computer program includes a plurality of
instructions including but not limited to one or more instructions
3320 for determining at least one comparison between information
regarding at least one aspect of cellular or tissue abrasion or
ablation of at least one biological tissue of at least one subject
and information regarding at least one clinical outcome following
receipt by the at least one subject of at least one frozen particle
composition (or frozen piercing implement). In one embodiment, the
system includes one or more instructions 3330 for determining at
least one statistical correlation. In one embodiment, the system
includes one or more instructions 3340 for counting the occurrence
of at least one clinical outcome. In one embodiment, information
regarding at least one aspect of cellular or tissue abrasion or
ablation includes information 3350 regarding quantity of cells or
tissue removed or destroyed; information 3360 regarding at least
one dimension of cellular, tissue or other material removal or
destruction; information 3370 regarding at least one of depth,
width, or breadth of cellular removal or destruction; or
information 3380 regarding two or more subjects with one or more
common attributes. In one embodiment, the information regarding at
least one aspect of cellular or tissue abrasion or ablation
includes information 3400 regarding at least one cellular or tissue
source, including information 3410 regarding at least one abnormal
cellular or tissue source or information 3420 regarding at least
one type of cell or tissue.
[0879] In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes at least one of polyethylene glycol, acetone,
ethyl acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, acetic acid, benzene, carbon tetrachloride, hexane,
methylene chloride, carboxylic acid, saline, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether 3430. In one embodiment, at least one
frozen particle composition (or frozen piercing implement) includes
at least one major dimension of approximately one decimeter or
less, approximately one centimeter or less, approximately one
millimeter or less, approximately one micrometer or less,
approximately one nanometer or less, or any value therebetween
3440. In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) includes one or more
reinforcement agents 3450. In one embodiment, the at least one
frozen particle composition (or frozen piercing implement) includes
one or more explosive materials 3460.
[0880] In one embodiment, the receipt by the at least one subject
of at least one frozen particle composition (or frozen piercing
implement) or therapeutic composition is pursuant to at least one
clinical trial 3500. In one embodiment, the system further
comprises one or more instructions for determining at least one
comparison before the delivery or administration of the at least
one frozen particle composition (or frozen piercing implement) or
therapeutic composition to at least one subject 3510.
[0881] In one embodiment, the system includes one or more
instructions for creating at least one inclusion criterion and at
least one exclusion criterion for a clinical trial involving the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition 3520. In one embodiment, the
system further comprises one or more instructions for suggesting
the inclusion of one or more of the at least one subject in at
least one clinical trial 3530. In certain instances, multiple
subjects from multiple clinical trials are included.
[0882] In one embodiment, the system further includes one or more
instructions for suggesting the exclusion of one or more of the at
least one subject in at least one clinical trial 3540. In one
embodiment, the system includes one or more instructions for using
one or more of the at least one comparison to predict at least one
clinical outcome regarding at least one second subject 3550. In one
embodiment, the at least one second subject has not received the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition 3560. In one embodiment, the
system includes predicting at least one clinical outcome involving
the at least one second subject, wherein the at least one second
subject is a plurality of people; and segregating subject
identifiers associated with the plurality of people in reference to
the predicted at least one clinical outcome 3570. In one
embodiment, the at least one second subject is a plurality of
people; and the system further comprises determining the
eligibility of the at least one second subject for the at least one
clinical trial 3580.
[0883] As indicated in FIG. 36, at least one aspect relates to a
system 3600 that includes at least one computer program 3610,
configured with a computer-readable medium, for use with at least
one computer system and wherein the computer program includes a
plurality of instructions including but not limited to one or more
instructions 3620 for comparing information regarding at least one
aspect of cellular or tissue abrasion or ablation of at least one
biological tissue of at least one subject and information regarding
at least one frozen particle composition (or frozen piercing
implement) involving the at least one biological tissue of at least
one subject; and one or more instructions 3630 for applying one or
more comparisons to information regarding at least one aspect of
cellular or tissue abrasion or ablation regarding a plurality of
people.
[0884] In one embodiment, one or more instructions 3640 for
segregating subject identifiers associated with the plurality of
people in reference to at least one of the one or more applied
comparisons. In one embodiment, the information regarding at least
one aspect of cellular or tissue abrasion or ablation includes
information 3650 regarding quantity of cells or tissue removed or
destroyed; information 3660 regarding at least one dimension of
cellular, tissue or other material removal or destruction; or
information 3670 regarding at least one of depth, width, or breadth
of cellular removal or destruction. In one embodiment, the system
includes one or more instructions 3680 for segregating individual
identifiers associated with the plurality of people in reference to
at least one characteristic shared by two or more subjects of the
plurality of people.
[0885] As indicated in FIG. 37, at least one aspect relates to a
method 3700 comprising accepting a first input 3710 associated with
at least one characteristic of at least one biological tissue to be
at least partially constructed or at least partially reconstructed;
accepting a second input 3720 associated with at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions (or frozen piercing
implements) including at least one agent. In one embodiment, the at
least one agent 3730 includes one or more of a therapeutic agent,
adhesive agent, abrasive, reinforcement agent, explosive material,
or biological remodeling agent. In one embodiment, administering
3740 the one or more frozen particle compositions (or frozen
piercing implements) includes administering the one or more frozen
particle compositions (or frozen piercing implements) to at least
one substrate. In one embodiment, the at least one substrate 3750
includes one or more of a cell, tissue, organ, structure, or
device.
[0886] In one embodiment, the method includes processing results
3760 of the first input and the second input. In one embodiment,
processing results of the first input and the second input includes
electronically processing 3770 results of the first input and the
second input. In one embodiment, processing results of the first
input and the second input includes 3780 electronically processing
results of the first input and the second input by utilizing one or
more of Gaussian smoothing, scaling, homomorphic filtering,
parametric estimation techniques, Boolean operations, Monte Carlo
simulations, wavelet based techniques, mirroring, smoothing,
gradient weighted partial differential equation smoothing, NURBS,
polygonal modeling, splines and patches modeling, algorithmic
execution, logical decision-making, result prediction, Finite
Element Analysis, or modification of a CAD design.
[0887] As indicated in FIG. 38, in one embodiment, the first input
3810 includes one or more values related to the at least one
characteristic of at least one biological tissue. In one
embodiment, the first input includes one or more spatial addresses
3820 associated with the at least one characteristic of at least
one biological tissue. In one embodiment, the first input includes
one or more of x, y, or z coordinates 3830 associated with the at
least one characteristic of at least one biological tissue.
[0888] In one embodiment, the at least one characteristic 3840 of
at least one biological tissue to be at least partially constructed
or at least partially reconstructed includes one or more of:
morphological feature, anatomical feature, histological feature,
tissue hierarchical level, scaffold feature, vascular structure
feature, heterogenous tissue feature, mechanical feature,
volumetric feature, geometric feature, volumetric representation,
mechanical feature, deformation, kinematic feature, surface contour
feature, cytometric feature, cell aggregation, cell growth,
cell-cell interaction, cell-tissue interaction, biomimetic design,
cell pattern, cell deposition, organ hierarchical level, tissue
microstructure, cellular microstructure, cell junction feature,
tissue junction feature, cell-tissue classification, hard tissue
classification, soft tissue classification, tumor diagnosis, or
other feature.
[0889] In one embodiment, the at least one characteristic 3850 of
at least one biological tissue includes one or more of cellular
type, cellular function, cellular size, cellular constitution,
cellular architecture, cellular durability, cellular source, tissue
type, tissue constitution, tissue size, tissue shape, tissue
function, tissue architecture, tissue source, tissue durability,
organ type, organ constitution, organ size, organ shape, organ
function, organ architecture, organ source, or organ durability. In
one embodiment, the first input 3860 includes one or more temporal
addresses associated with the at least one characteristic of at
least one biological tissue.
[0890] As indicated in FIG. 39, in one embodiment, the first input
3910 includes one or more values derived from at least one image of
the at least one biological tissue. In one embodiment, the at least
one image 3920 includes one or more images acquired by one or more
of laser, holography, x-ray crystallography, optical coherence
tomography, computer-assisted tomography scan, computed tomography,
magnetic resonance imaging, positron-emission tomography scan,
ultrasound, x-ray, electrical-impedance monitoring, microscopy,
spectrometry, flow cytommetry, radioisotope imaging, thermal
imaging, multiphoton calcium-imaging, photography, or in silico
generation.
[0891] In one embodiment, the at least one biological tissue 3930
is located in at least one of in situ, in vitro, in vivo, in utero,
in planta, in silico, or ex vivo. In one embodiment, the at least
one biological tissue 3940 is at least partially located in at
least one subject. In one embodiment, the method further comprises
accepting a third input 3950 associated with at least one feature
of the at least one subject. In one embodiment, the at least one
feature 3960 of the at least one subject includes one or more of
age, gender, genotype, phenotype, proteomic profile, or health
condition.
[0892] As indicated in FIGS. 40-41, in one embodiment, the
processing results 4010 of the first input and the second input
includes determining at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue with one or more frozen particle compositions (or
frozen piercing implements) from one or more values derived from at
least one image of the at least one biological tissue. In one
embodiment, the second input 4020 includes one or more values
related to the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue by administering one or more frozen particle
compositions (or frozen piercing implements) to the at least one
substrate. In one embodiment, 4130 the one or more values related
to the at least one parameter of constructing or reconstructing the
at least one biological tissue includes one or more predictive
values.
[0893] In one embodiment, the at least one parameter 4030 of at
least partially constructing or at least partially reconstructing
the at least one biological tissue includes one or more of porosity
of the at least one substrate, pore size of the at least one
substrate, interconnectivity of the pores of the at least one
substrate, transport properties of the at least one substrate,
cell-tissue formation of the at least one substrate, mechanical
strength of the at least one substrate, ability for attachment or
distribution of the at least one agent included in the one or more
frozen particle compositions (or frozen piercing implements) to the
at least one substrate, ability for attachment or distribution of
one or more cells or tissues to the at least one substrate,
facilitation of at least one nutrient, or tissue formation or
tissue growth associated with the at least one substrate.
[0894] In one embodiment, the at least one parameter 4040 of at
least partially constructing or at least partially reconstructing
the at least one biological tissue by administering one or more
frozen particle compositions (or frozen piercing implements)
includes one or more of: design of plot or model for administration
of one or more frozen particle compositions(or frozen piercing
implements), constitution of the one or more frozen particle
compositions (or frozen piercing implements), formulation of the
one or more frozen particle compositions (or frozen piercing
implements), size of the one or more frozen particle compositions
(or frozen piercing implements), shape of the one or more frozen
particle compositions (or frozen piercing implements), angle of
administration of the one or more frozen particle compositions (or
frozen piercing implements), velocity of administration of the one
or more frozen particle compositions (or frozen piercing
implements), quantity of frozen particle compositions (or frozen
piercing implements) administered, rate of administration of more
than one frozen particle composition (or frozen piercing
implement), spatial location for administration of one or more
frozen particle compositions (or frozen piercing implements),
temporal location for administration of one or more frozen particle
compositions (or frozen piercing implements), method of
administration of one or more frozen particle compositions (or
frozen piercing implements), timing of administration of one or
more frozen particle compositions (or frozen piercing implements),
modulation of administration of one or more frozen particle
compositions (or frozen piercing implements), deposition of one or
more frozen particle compositions (or frozen piercing implements),
or rate of deposition of at least one agent.
[0895] In one embodiment, the at least one parameter 4110 of at
least partially constructing or at least partially reconstructing
the at least one biological tissue by administering one or more
frozen particle compositions (or frozen piercing implements)
includes at least one parameter relating to at least partially
ablating or at least partially abrading one or more surfaces of the
at least one biological tissue with the one or more frozen particle
compositions (or frozen piercing implements).
[0896] In one embodiment, the at least one parameter 4120 of at
least partially constructing or at least partially reconstructing
the at least one biological tissue by administering one or more
frozen particle compositions (or frozen piercing implements)
includes at least one parameter relating to administering at least
one of a therapeutic agent, adhesive agent, biological remodeling
agent, reinforcement agent, abrasive, or explosive material with
the one or more frozen particle compositions (or frozen piercing
implements).
[0897] In one embodiment, the spatial location 4140 for
administration of one or more frozen particle compositions (or
frozen piercing implements)includes one or more of x, y, or z
coordinates. In one embodiment, the processing results 4150
includes comparing at least one value related to the first input
associated with the at least one characteristic of at least one
biological tissue to be at least partially constructed or at least
partially reconstructed with at least one value related to at least
one image of a target biological tissue. In one embodiment 4160,
the image of a target biological tissue includes an image of a
similar biological tissue, or an image of a dissimilar biological
tissue.
[0898] As indicated in FIG. 42, the processing results 4210
includes comparing at least one value related to the second input
associated with the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue with at least one value related to another
administration of one or more frozen particle compositions (or
frozen piercing implements). In one embodiment 4220, the processing
results includes determining one or more differences in at least
one value related to the first input and at least one value related
to at least one image of the at least one biological tissue or a
similar biological tissue. In one embodiment 4230, the processing
results includes determining one or more differences in at least
one value related to the second input associated with the at least
one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue and at
least one value related to another administration of one or more
frozen particle compositions (or frozen piercing implements) to the
at least one substrate.
[0899] In one embodiment 4240, the processing results includes
generating one or more protocols for administering the one or more
frozen particle compositions (or frozen piercing implements). In
one embodiment 4250, the processing results includes generating one
or more blueprints for administering the one or more frozen
particle compositions (or frozen piercing implements). In one
embodiment 4260, the one or more blueprints include at least one of
a two-dimensional plot or a three-dimensional model. In one
embodiment 4270, the one or more blueprints include at least one
representation of at least one of organ anatomy, morphology, tissue
heterogeneity, scale of vascular system, geometry, internal
architecture of an organ or tissue, internal or external boundary
distinction of a tissue or organ, topology, or tomography.
[0900] As indicated in FIG. 43, the processing results 4310
includes: comparing one or more values related to the one or more
characteristics of the at least one biological tissue that are
determined at two or more different times to obtain one or more
characteristic comparisons; comparing one or more values related to
the at least one parameter of at least partially constructing or at
least partially reconstructing the at least one biological tissue
at two or more different times to obtain one or more parameter
comparisons; comparing the one or more characteristic comparisons
with the one or more parameter comparisons to obtain one or more
characteristic-characteristic/parameter-parameter comparisons; and
comparing the one or more
characteristic-characteristic/parameter-parameter comparisons to
one or more substantially similar results obtained for one or more
other at least partially constructed or at least partially
reconstructed biological tissues. In one embodiment 4320, the
administering one or more frozen particle compositions (or frozen
piercing implements) includes depositing the at least one agent on
the at least one substrate.
[0901] As indicated in FIG. 44, the method further comprises 4410
displaying results of the processing. In one embodiment 4420, the
displaying results of the processing includes displaying the
results on one or more active displays. In one embodiment 4430, the
displaying results of the processing includes displaying the
results on one or more passive displays. In one embodiment 4440,
the displaying results of the processing includes displaying the
results of the processing in at least one of numeric format,
graphical format, or audio format.
[0902] In one embodiment 4450, the displaying results of the
processing includes displaying a comparison of at least one
biological tissue that has been at least partially constructed or
at least partially reconstructed. In one embodiment 4460, the
displaying results of the processing includes displaying a
comparison of at least one subject with one or more other subjects.
In one embodiment 4470, the displaying results of the processing
includes displaying one or more differences in the comparison of at
least one value related to the first input and at least one value
related to at least one image of a biological tissue. In one
embodiment 4480, the displaying results of the processing includes
displaying one or more differences in the comparison of at least
one value related to the second input and at least one value
related to another administration of one or more frozen particle
compositions (or frozen piercing implements).
[0903] As indicated in FIG. 45, the method further comprises
transmitting 4510 one or more signals that include information
related to the processing results of the first input and the second
input. In one embodiment 4520, the transmitting one or more signals
includes transmitting one or more signals associated with selection
of one or more frozen particle compositions (or frozen piercing
implements) for administration. In one embodiment 4530, the
transmitting one or more signals includes transmitting one or more
signals associated with selection of one or more of a biological
remodeling agent, adhesive agent, abrasive, therapeutic agent,
reinforcement agent, or explosive material associated with the one
or more frozen particle compositions (or frozen piercing
implements). In one embodiment 4540, the transmitting one or more
signals includes transmitting one or more signals associated with
comparing the information related to the processing results of the
first input and the second input.
[0904] As indicated in FIG. 46, the one or more frozen particle
compositions (or frozen piercing implements) 4610 include one or
more frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, methane, or diethyl
ether.
[0905] In one embodiment 4620, the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 4630, at least one of the adhesive agent,
therapeutic agent, reinforcement agent, abrasive, explosive
material, or biological remodeling agent is substantially in the
form of at least one of an organic or inorganic small molecule,
clathrate or caged compound, protocell, coacervate, microsphere,
Janus particle, proteinoid, laminate, helical rod, liposome,
macroscopic tube, niosome, sphingosome, toroid, vesicular tube,
vesicle, small unilamellar vesicle, large unilamellar vesicle,
large multilamellar vesicle, multivesicular vesicle, lipid layer,
lipid bilayer, micelle, organelle, cell, membrane, nucleic acid,
peptide, polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
[0906] As indicated in FIG. 47, the one or more explosive materials
4710 include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal. In one embodiment 4720, the at least one adhesive
agent includes one or more of an acrylic polymer or copolymer,
acrylamide polymer or copolymer polymer or copolymer, acrylamide
polymer or copolymer, polyacrylic acid, epoxy, urethane, gum
arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or
gelatin.
[0907] In at least one embodiment 4730, the one or more
reinforcement agents include one or more of polyaramid, vinylester
matrix, metal, ceramic, cotton, hemp, fiberglass, cellulose, broad
carbide, aromatic polyamide, nylon, silk, rayon, acetate,
modacrylic, olefin, acrylic, polyester, aromatic polyester,
poly-lactic acid, vinyon, saran, spandex, vinalon, aromatic nylon,
vinylidene chloride, modal, polybenzimidazole, sulfur, lyocell,
orlon, zylon, high-performance polyethylene,
polypyridobenzimidazole, vectran, acrylonitrile rubber, glass,
copper, iron, steel, sodium, potassium, calcium, zinc, manganese,
carbon, magnesium, silicon, silica, frozen hydrogen oxide ice,
plant matter, animal matter, or mineral matter.
[0908] As indicated in FIG. 48, the therapeutic agent 4810 includes
at least one of an anti-tumor agent, antimicrobial agent,
anti-viral agent, analgesic, antiseptic, anesthetic, diagnostic
agent, anti-inflammatory agent, vaccine, cell growth inhibitor,
cell growth promoter, immunogen, antigen, radioactive agent,
apoptosis promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
[0909] In one embodiment 4820 the at least one biological
remodeling agent includes one or more of a blood cell, chondrocyte,
endothelial cell, hepatocyte, keratinocyte, myocyte, osteoblast,
osteoclast, osteocyte, mesenchymal cell, stem cell, progenitor
cell, or fibroblast. In one embodiment, 4830, the at least one
biological remodeling agent includes one or more of calcium
phosphate, albumin, cytokine, pegylated cytokine, bone, cartilage,
globulin, fibrin, thrombin, glutaraldehyde-crosslinked pericardium,
hide powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 4840, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin. In one
embodiment 4850, the at least one biological remodeling agent is
included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
[0910] As indicated in FIGS. 49-51, a method 4900 comprises
accepting input 4910 associated with at least one parameter of at
least partially constructing or at least partially reconstructing
at least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements);
administering 4920 one or more frozen particle compositions (or
frozen piercing implements) including at least one agent;
[0911] wherein 4930 the at least one agent includes one or more of
a biological remodeling agent, therapeutic agent, reinforcement
agent, explosive material, abrasive, or adhesive agent; evaluating
4940 the at least one biological tissue for one or more indicators
related to deposition of at least one agent, tissue formation, or
tissue growth; and transmitting 5110 one or more signals that
include information related to the accepting input and information
related to the evaluating the at least one biological tissue.
[0912] In one embodiment 4950, the evaluating at least one
biological tissue for one or more indicators includes evaluating at
least one of an assay, image, or gross assessment of the at least
one biological tissue prior to, during, or subsequent to at least
one administration of the one or more frozen particle compositions
(or frozen piercing implements). In one embodiment 4960, the assay
includes at least one technique that includes spectroscopy,
microscopy, electrochemical detection, polynucleotide detection,
histological examination, biopsy analysis, fluorescence resonance
energy transfer, electron transfer, enzyme assay, electrical
conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay.
[0913] In one embodiment 5020, the image includes at least one
image acquired by one or more of laser, holography, x-ray
crystallography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, multiphoton
calcium-imaging, photography, or in silico generation. In one
embodiment 5030, wherein the one or more indicators of tissue
formation or growth include at least one of cell migration, cell
attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, diffusion of materials, angiogenesis,
nucleic acid expression, protein translation, protein modification,
carbohydrate production, carbohydrate secretion, fat production,
fat secretion, or protein secretion.
[0914] In one embodiment 5040, the input associated with at least
one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue by
administering one or more frozen particle compositions (or frozen
piercing implements) includes one or more of: constitution of the
one or more frozen particle compositions (or frozen piercing
implements), formulation of the one or more frozen particle
compositions (or frozen piercing implements), size of the one or
more frozen particle compositions (or frozen piercing implements),
shape of the one or more frozen particle compositions (or frozen
piercing implements), angle of administration of the one or more
frozen particle compositions (or frozen piercing implements),
velocity of administration of the one or more frozen particle
compositions (or frozen piercing implements), quantity of frozen
particle compositions (or frozen piercing implements) administered,
rate of administration of more than one frozen particle composition
(or frozen piercing implement), spatial location for administration
of one or more frozen particle compositions (or frozen piercing
implements), temporal location for administration of one or more
frozen particle compositions (or frozen piercing implements),
method of administration of one or more frozen particle
compositions (or frozen piercing implements), timing of
administration of one or more frozen particle compositions (or
frozen piercing implements), modulation of administration of one or
more frozen particle compositions (or frozen piercing implements),
deposition of one or more frozen particle compositions (or frozen
piercing implements), or rate of deposition of at least one
agent.
[0915] In one embodiment 5120, the transmitting one or more signals
includes transmitting one or more signals associated with selection
of one or more frozen particle compositions (or frozen piercing
implements) for administration. In one embodiment 5130, the
transmitting one or more signals includes transmitting one or more
signals associated with selection of one or more of a biological
remodeling agent, adhesive agent, abrasive, therapeutic agent,
reinforcement agent, or explosive material associated with the one
or more frozen particle compositions (or frozen piercing
implements). In one embodiment 5140, the administering one or more
frozen particle compositions (or frozen piercing implements)
includes administering the one or more frozen particle compositions
(or frozen piercing implements) to at least one substrate. In one
embodiment 5150, the at least one substrate includes one or more of
a cell, tissue, organ, structure, or device. In one embodiment
5160, the one or more frozen particle compositions (or frozen
piercing implements) include one or more frozen particles including
at least one of hydrogen oxide, nitrogen, oxygen, air, helium,
neon, argon, xenon, chlorine, bromine, carbon dioxide, acetone,
ethyl acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
tetrahydrofuran, acetronitrile, acetic acid, n-butanol,
isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, standard saline citrate, methane, toluene, chloroform,
polyethylene glycol, acetic acid, Ringer's solution, lactated
Ringer's solution, Hartmann's solution, acetated Ringer's solution,
phosphate buffered solution, TRIS-buffered saline solution, Hank's
balanced salt solution, Earle's balanced salt solution, standard
saline citrate, HEPES-buffered saline, dextrose, glucose, methane,
or diethyl ether.
[0916] As indicated in FIG. 52, the at least one agent 5210
includes one or more of an adhesive agent, therapeutic agent,
reinforcement agent, abrasive, explosive material, or biological
remodeling agent. In one embodiment 5220, the adhesive agent,
therapeutic agent, reinforcement agent, abrasive, explosive
material, or biological remodeling agent is substantially in the
form of at least one of an organic or inorganic small molecule,
clathrate or caged compound, protocell, coacervate, microsphere,
Janus particle, proteinoid, laminate, helical rod, liposome,
macroscopic tube, niosome, sphingosome, toroid, vesicular tube,
vesicle, small unilamellar vesicle, large unilamellar vesicle,
large multilamellar vesicle, multivesicular vesicle, lipid layer,
lipid bilayer, micelle, organelle, cell, membrane, nucleic acid,
peptide, polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
[0917] In one embodiment 5230, the one or more explosive materials
include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal.
[0918] In one embodiment 5240, the at least one adhesive agent
includes one or more of an acrylic polymer or copolymer, acrylamide
polymer or copolymer polymer or copolymer, acrylamide polymer or
copolymer, polyacrylic acid, epoxy, urethane, gum arabic,
polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or
gelatin.
[0919] As indicated in FIG. 53, the one or more reinforcement
agents 5310 include one or more of polyaramid, vinylester matrix,
metal, ceramic, fiberglass, cellulose, broad carbide, aromatic
polyamide, nylon, silk, rayon, acetate, modacrylic, olefin,
acrylic, polyester, aromatic polyester, poly-lactic acid, vinyon,
saran, spandex, vinalon, aromatic nylon, vinylidene chloride,
modal, polybenzimidazole, sulfur, lyocell, orlon, zylon,
high-performance polyethylene, polypyridobenzimidazole, vectran,
acrylonitrile rubber, glass, copper, iron, steel, sodium,
potassium, calcium, zinc, manganese, carbon, magnesium, silicon,
silica, frozen hydrogen oxide ice, plant matter, animal matter, or
mineral matter.
[0920] In one embodiment 5320, the therapeutic agent includes at
least one of an anti-tumor agent, antimicrobial agent, anti-viral
agent, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof. In one embodiment 5330, the at least
one biological remodeling agent includes one or more of a blood
cell, chondrocyte, endothelial cell, hepatocyte, keratinocyte,
myocyte, osteoblast, osteoclast, osteocyte, mesenchymal cell, stem
cell, progenitor cell, or fibroblast.
[0921] In one embodiment 5340, the at least one biological
remodeling agent includes one or more of calcium phosphate,
albumin, cytokine, pegylated cytokine, bone, cartilage, globulin,
fibrin, thrombin, glutaraldehyde-crosslinked pericardium, hide
powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin.
[0922] In one embodiment 5350, the at least one biological
remodeling agent includes one or more of Type I collagen, Type II
collagen, Type III collagen, Type VII collagen, Type X collagen,
elastin fibers, or soluble elastin.
[0923] As indicated in FIG. 54, a method 5400 comprises receiving
5410 one or more signals that include information related to
accepting input associated with at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements); receiving
5420 one or more signals that include information related to
evaluating the at least one biological tissue for one or more
indicators of tissue formation or growth; and processing 5430 the
information related to the input associated with at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue and the
information related to the evaluating the at least one biological
tissue. In one embodiment 5440, the evaluating at least one
biological tissue for one or more indicators includes evaluating at
least one of an assay, image, or gross assessment of the at least
one biological tissue prior to, during, or subsequent to at least
one administration of one or more frozen particle compositions (or
frozen piercing implements).
[0924] In one embodiment 5450, the assay includes at least one
technique that includes spectroscopy, microscopy, electrochemical
detection, polynucleotide detection, histological examination,
biopsy analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment 5460, the image includes at
least one image acquired by one or more of optical coherence
tomography, computer-assisted tomography scan, computed tomography,
magnetic resonance imaging, positron-emission tomography scan,
ultrasound, x-ray, x-ray crystallography, laser, holography,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, multiphoton
calcium-imaging, photography, or in silico generation.
[0925] As indicated in FIG. 55, the one or more indicators 5510 of
tissue formation or growth include at least one of: cell migration,
cell attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, diffusion of materials, angiogenesis,
nucleic acid expression, protein translation, protein modification,
carbohydrate production, carbohydrate secretion, fat production,
fat secretion, or protein secretion.
[0926] In one embodiment 5520, the input associated with at least
one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue
includes one or more of constitution of the one or more frozen
particle compositions (or frozen piercing implements), formulation
of the one or more frozen particle compositions (or frozen piercing
implements), size of the one or more frozen particle compositions
(or frozen piercing implements), shape of the one or more frozen
particle compositions (or frozen piercing implements), angle of
administration of the one or more frozen particle compositions (or
frozen piercing implements), velocity of administration of the one
or more frozen particle compositions (or frozen piercing
implements), quantity of frozen particle compositions (or frozen
piercing implements) administered, rate of administration of more
than one frozen particle composition(or frozen piercing implement),
spatial location for administration of one or more frozen particle
compositions (or frozen piercing implements), temporal location for
administration of one or more frozen particle compositions (or
frozen piercing implements), method of administration of one or
more frozen particle compositions (or frozen piercing implements),
timing of administration of one or more frozen particle
compositions (or frozen piercing implements), modulation of
administration of one or more frozen particle compositions (or
frozen piercing implements), deposition of one or more frozen
particle compositions (or frozen piercing implements), or rate of
deposition of at least one agent.
[0927] In one embodiment 5530, the receiving one or more signals
includes receiving one or more signals associated with selection of
one or more frozen particle compositions
[0928] (or frozen piercing implements) for administration. In one
embodiment 5540, the receiving one or more signals includes
receiving one or more signals associated with the selection of at
least one of a biological remodeling agent, adhesive agent,
abrasive, therapeutic agent, reinforcement agent, or explosive
material associated with the one or more frozen particle
compositions (or frozen piercing implements).
[0929] As indicated in FIG. 56, in one embodiment 5610, the
administering one or more frozen particle compositions (or frozen
piercing implements) includes administering the one or more frozen
particle compositions (or frozen piercing implements) to at least
one substrate. In one embodiment 5620, the at least one substrate
includes one or more of a cell, tissue, organ, structure, or
device. In one embodiment 5630, the one or more frozen particle
compositions (or frozen piercing implements) include one or more
frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, methane, or diethyl
ether.
[0930] In one embodiment 5640, the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 5650, the adhesive agent, therapeutic
agent, reinforcement agent, abrasive, explosive material, or
biological remodeling agent is substantially in the form of at
least one of an organic or inorganic small molecule, clathrate or
caged compound, protocell, coacervate, microsphere, Janus particle,
proteinoid, laminate, helical rod, liposome, macroscopic tube,
niosome, sphingosome, toroid, vesicular tube, vesicle, small
unilamellar vesicle, large unilamellar vesicle, large multilamellar
vesicle, multivesicular vesicle, lipid layer, lipid bilayer,
micelle, organelle, cell, membrane, nucleic acid, peptide,
polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
[0931] As indicated in FIG. 57, the one or more explosive materials
5710 include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal. In one embodiment 5720, the at least one adhesive
agent includes one or more of an acrylic polymer or copolymer,
acrylamide polymer or copolymer polymer or copolymer, acrylamide
polymer or copolymer, polyacrylic acid, epoxy, urethane, gum
arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or gelatin.
In one embodiment 5730, the one or more reinforcement agents
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
[0932] In one embodiment 5740, the therapeutic agent includes at
least one of an anti-tumor agent, antimicrobial agent, anti-viral
agent, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
[0933] In one embodiment 5810, the at least one biological
remodeling agent includes one or more of a blood cell, chondrocyte,
endothelial cell, hepatocyte, keratinocyte, myocyte, osteoblast,
osteoclast, osteocyte, mesenchymal cell, stem cell, progenitor
cell, or fibroblast. In one embodiment 5820, the at least one
biological remodeling agent includes one or more of calcium
phosphate, albumin, cytokine, pegylated cytokine, bone, cartilage,
globulin, fibrin, thrombin, glutaraldehyde-crosslinked pericardium,
hide powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 5830, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin.
[0934] In one embodiment 5840, the at least one biological
remodeling agent is included as part of a carrier that assists in
synthesis or activation of the at least one biological remodeling
agent.
[0935] As indicated in FIG. 59, a method 5900 comprises comparing
information 5910 regarding at least one parameter for at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject by administering one or
more frozen particle compositions (or frozen piercing implements)
to the at least one subject and information regarding at least one
clinical outcome following receipt by the at least one subject of
one or more frozen particle compositions (or frozen piercing
implements); and providing output information 5920. In one
embodiment 5930, the output information is based on the comparison.
In one embodiment 5940, the method further comprises determining at
least one statistical correlation. In one embodiment 5950, the
method further comprises counting the occurrence of at least one
clinical outcome. In one embodiment 5960, the information regarding
at least one parameter of at least partially constructing or at
least partially reconstructing at least one biological tissue of a
subject includes information regarding quantity of cells or tissue
at least partially constructed or at least partially reconstructed.
In one embodiment 5970, the information regarding at least one
parameter of at least partially constructing or at least partially
reconstructing at least one biological tissue of a subject includes
information regarding at least one cellular or tissue source. In
one embodiment 5980, the information regarding at least one
parameter of at least partially constructing or at least partially
reconstructing at least one biological tissue of a subject includes
information regarding at least one abnormal cellular or tissue
source. In one embodiment 5990, the information regarding at least
one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of a
subject includes information regarding at least one type of cell or
tissue.
[0936] As indicated in FIG. 60, the at least one agent 6010
includes at least one agent including at least one adhesive agent,
abrasive, reinforcement agent, therapeutic agent, biological
remodeling agent, or explosive material. In one embodiment 6020,
the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject includes information
regarding at least one dimension of at least one agent deposited.
In one embodiment 6030, the information regarding at least one
parameter of at least partially constructing or at least partially
reconstructing at least one biological tissue of at least one
subject includes information regarding at least one dimension of at
least one depth, width, or breadth of cellular, tissue, or other
material removal or destruction. In one embodiment 6040, the
information regarding at least one clinical outcome following
receipt by the at least one subject of one or more frozen particle
compositions (or frozen piercing implements) includes information
regarding two or more subjects with one or more common
attributes.
[0937] In one embodiment 6050, the one or more common attributes
include one or more of genetic attributes, mental attributes,
proteomic attributes, phenotypic attributes, or psychological
attributes. In one embodiment 6060, the one or more common
attributes include one or more of height, weight, medical
diagnosis, familial background, results on one or more medical
tests, ethnic background, body mass index, age, presence or absence
of at least one disease or condition, species, ethnicity, race,
allergies, gender, thickness of tissue, blood vessel condition,
hair or fur condition, skin condition, tissue condition, muscle
condition, organ condition, nerve condition, brain condition,
presence or absence of at least one biological, chemical, or
therapeutic agent in the subject, pregnancy status, lactation
status, genetic profile, proteomic profile, partial or whole
genetic sequence, partial or whole proteomic sequence, medical
condition, medical history, or blood condition.
[0938] As indicated in FIG. 61, the output information 6110
includes at least one of a response signal, comparison code,
comparison plot, diagnostic code, treatment code, test code, code
indicative of at least one treatment received, code indicative of
at least one prescribed treatment step, code indicative of at least
one vaccination administered, code indicative of at least one
therapeutic agent administered, code indicative of at least one
diagnostic agent administered, code indicative of at least one
interaction of an administered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispertion or location of at least one administered agent; code
indicative of at least one detection material administered; code
indicative of the depth of penetration of an administered agent,
code indicative of the depth of deposition of an administered
agent, or a code indicative of the condition of at least one
location of an administered frozen particle composition (or frozen
piercing implement).
[0939] In one embodiment 6120, receipt by the at least one subject
of one or more frozen particle compositions (or frozen piercing
implements) is pursuant to at least one clinical trial. In one
embodiment 6130, the method further comprises determining at least
one correlation before the administration of the one or more frozen
particle compositions (or frozen piercing implements) to the at
least one subject.
[0940] In one embodiment 6140, the method further comprises
creating at least one inclusion criterion and at least one
exclusion criterion for a clinical trial involving the one or more
frozen particle compositions (or frozen piercing implements). In
one embodiment 6150, the method further comprises suggesting the
inclusion of one or more of the at least one subject in at least
one clinical trial. In one embodiment 6160, the method further
comprises suggesting the exclusion of one or more of the at least
one subject in at least one clinical trial.
[0941] As indicated in FIG. 62, the method further comprising using
one or more of the at least one correlation 6210 to predict at
least one clinical outcome regarding at least one second subject.
In one embodiment 6220, the at least one second subject has not
received the one or more frozen particle compositions (or frozen
piercing implements). In one embodiment 6230, the method further
comprises predicting at least one clinical outcome involving the at
least one second subject, wherein the at least one second subject
is a plurality of people; and segregating subject identifiers
associated with the plurality of people in reference to the
predicted at least one clinical outcome. In one embodiment 6240,
the method further comprises determining the eligibility of the at
least one second subject for the at least one clinical trial.
[0942] In one embodiment 6250, the one or more frozen particle
compositions (or frozen piercing implements) include one or more
frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, methane, or diethyl
ether.
[0943] As indicated in FIG. 63, the at least one agent 6310
includes one or more of an adhesive agent, therapeutic agent,
reinforcement agent, abrasive, explosive material, or biological
remodeling agent. In one embodiment 6320, the adhesive agent,
therapeutic agent, reinforcement agent, abrasive, explosive
material, or biological remodeling agent is substantially in the
form of at least one of an organic or inorganic small molecule,
clathrate or caged compound, protocell, coacervate, microsphere,
Janus particle, proteinoid, laminate, helical rod, liposome,
macroscopic tube, niosome, sphingosome, toroid, vesicular tube,
vesicle, small unilamellar vesicle, large unilamellar vesicle,
large multilamellar vesicle, multivesicular vesicle, lipid layer,
lipid bilayer, micelle, organelle, cell, membrane, nucleic acid,
peptide, polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer. In one
embodiment 6330, the one or more explosive materials include at
least one of a carbonate, carbon dioxide, nitroglycerine, acid,
base, epoxy, acrylic polymer or copolymer, acrylamide polymer or
copolymer, urethane, hypoxyapatite, or reactive metal. In one
embodiment 6340, the at least one adhesive agent includes one or
more of an acrylic polymer or copolymer, acrylamide polymer or
copolymer polymer or copolymer, acrylamide polymer or copolymer,
polyacrylic acid, epoxy, urethane, gum arabic, polyester,
polyhydroxyalkanoate, poly(L-lactic acid), polyglycolide,
polylactic acid, polyether, polyol, polyvinylpyrrolidone,
pyroxylin, polymethylacrylate-isobutene-monoisopropylmaleate,
siloxane polymer, polylactic-co-glycolic-acid,
poly-3-hydroxybutyrate, poly-4-hydroxybutyrate,
polyhydroxyvalerate, polydydroxyhexanoate, polydyroxyoctanoate,
polycaprolactone, poly (e-caprolactone), sialyl Lewis.sup.x, heme
group, hemoglobin, healon, carboxymethylcellulose, hydroxyapatite,
silicone, cadherin, integrin, hydroxyapatite, polyelectrolyte,
maleic polyelectrolyte, cellulose, resilin, cyanoacrylate,
isocyanate, 2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate,
n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl
2-cyanoacrylate, polyisohexylcyanoacrylate, fibrin, thrombin,
fibrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk,
nylon, collagen, glycosaminoglycan, selectin, polyurethane,
methacrylate, or polysulfide, polyanhydride, polydioxanone,
poly-p-dioxanone, silicone, albumin, glutaraldehyde, polyethylene
glycol, or gelatin.
[0944] As indicated in FIG. 64, the one or more reinforcement
agents 6410 include one or more of polyaramid, vinylester matrix,
metal, ceramic, fiberglass, cellulose, broad carbide, aromatic
polyamide, nylon, silk, rayon, acetate, modacrylic, olefin,
acrylic, polyester, aromatic polyester, poly-lactic acid, vinyon,
saran, spandex, vinalon, aromatic nylon, vinylidene chloride,
modal, polybenzimidazole, sulfur, lyocell, orlon, zylon,
high-performance polyethylene, polypyridobenzimidazole, vectran,
acrylonitrile rubber, glass, copper, iron, steel, sodium,
potassium, calcium, zinc, manganese, carbon, magnesium, silicon,
silica, frozen hydrogen oxide ice, plant matter, animal matter, or
mineral matter.
[0945] In one embodiment 6420, the therapeutic agent includes at
least one of an anti-tumor agent, antimicrobial agent, anti-viral
agent, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof. In one embodiment 6430, the at least
one biological remodeling agent includes one or more of a blood
cell, chondrocyte, endothelial cell, hepatocyte, keratinocyte,
myocyte, osteoblast, osteoclast, osteocyte, mesenchymal cell, stem
cell, progenitor cell, or fibroblast.
[0946] As indicated in FIG. 65, the at least one biological
remodeling agent 6510 includes one or more of calcium phosphate,
albumin, cytokine, pegylated cytokine, bone, cartilage, globulin,
fibrin, thrombin, glutaraldehyde-crosslinked pericardium, hide
powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 6520, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin. In one
embodiment 6530, the at least one biological remodeling agent is
included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
[0947] As indicated in FIG. 66, a method 6600 of predicting a
clinical outcome of one or more frozen particle composition (or
frozen piercing implement) treatments for at least one first
subject, comprises determining 6610 a similarity or a dissimilarity
in information regarding at least one parameter for at least
partially constructing or at least partially reconstructing at
least one biological tissue of at least one first subject by
administering one or more frozen particle compositions (or frozen
piercing implements) to the at least one first subject with
information regarding at least one parameter of at least partially
constructing or at least partially reconstructing at least one
biological tissue of at least one second subject, wherein the at
least one second subject 6620 attained a clinical outcome following
receipt of one or more frozen particle compositions (or frozen
piercing implements); and providing output information 6630.
[0948] In one embodiment 6640, providing output information is
based on the determination. In one embodiment 6650, the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least second subject includes information regarding quantity
of cells or tissue at least partially constructed or at least
partially reconstructed. In one embodiment 6660, the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one first subject includes information regarding at
least one cellular or tissue source. In one embodiment 6670, the
information regarding at least one parameter of at least partially
constructing or at least partially reconstructing at least one
biological tissue of at least one first subject includes
information regarding at least one abnormal cellular or tissue
source.
[0949] As indicated in FIG. 67, the information 6710 regarding at
least one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of at least
one first subject includes information regarding at least one type
of cell or tissue. In one embodiment 6720, the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one second subject includes information regarding at
least one type of cell or tissue. In one embodiment 6730, the at
least one agent includes one or more of an adhesive agent,
abrasive, reinforcement agent, therapeutic agent, biological
remodeling agent, or explosive material. In one embodiment 6740,
the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of at least one first subject includes
information regarding at least one dimension of at least one agent
deposited.
[0950] In one embodiment 6750, the information regarding at least
one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of at least
one second subject includes information regarding at least one
dimension of at least one agent deposited. In one embodiment 6760,
the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of at least one second subject includes
information regarding at least one dimension of at least one depth,
width, or breadth of cellular, tissue, or other material removal or
destruction. In one embodiment 6770, the information regarding at
least one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of at least
one first subject includes information regarding at least one
dimension of at least one depth, width, or breadth of cellular,
tissue, or other material removal or destruction.
[0951] As indicated in FIG. 68, the information 6810 regarding at
least one clinical outcome following receipt by the at least one
second subject of one or more frozen particle compositions (or
frozen piercing implements) includes information regarding two or
more subjects with one or more common attributes. In one embodiment
6820, the one or more common attributes include one or more of
genetic attributes, mental attributes, proteomic attributes,
phenotypic attributes, or psychological attributes. In one
embodiment 6830, the one or more common attributes include one or
more of height, weight, medical diagnosis, familial background,
results on one or more medical tests, ethnic background, body mass
index, age, presence or absence of at least one disease or
condition, species, ethnicity, race, allergies, gender, thickness
of tissue, blood vessel condition, hair or fur condition, skin
condition, tissue condition, muscle condition, organ condition,
nerve condition, brain condition, presence or absence of at least
one biological, chemical, or therapeutic agent in the subject,
pregnancy status, lactation status, genetic profile, proteomic
profile, partial or whole genetic sequence, partial or whole
proteomic sequence, medical condition, medical history, or blood
condition. In one embodiment 6840, the output information includes
at least one of a response signal, comparison code, comparison
plot, diagnostic code, treatment code, test code, code indicative
of at least one treatment received, code indicative of at least one
prescribed treatment step, code indicative of at least one
vaccination administered, code indicative of at least one
therapeutic agent administered, code indicative of at least one
diagnostic agent administered, code indicative of at least one
interaction of an administered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one administered agent; code
indicative of at least one detection material administered; code
indicative of the depth of penetration of an administered agent,
code indicative of the depth of deposition of an administered
agent, or a code indicative of the condition of at least one
location of an administered frozen particle composition (or frozen
piercing implement).
[0952] As indicated in FIG. 69, in one embodiment 6910, receipt by
the at least one second subject of one or more frozen particle
compositions (or frozen piercing implements) is pursuant to at
least one clinical trial. In one embodiment 6920, the method
further comprises determining at least one correlation before the
administration of the one or more frozen particle compositions (or
frozen piercing implements) to the at least one first subject. In
one embodiment 6930, the method further comprises creating at least
one inclusion criterion and at least one exclusion criterion for a
clinical trial involving the one or more frozen particle
compositions (or frozen piercing implements). In one embodiment
6940, the method further comprises suggesting the inclusion of one
or more of the at least one first subject in at least one clinical
trial. In one embodiment 6950, the method further comprises
suggesting the exclusion of one or more of the at least one first
subject in at least one clinical trial.
[0953] In one embodiment 6960, the method further comprises using
one or more of the at least one correlation to predict at least one
clinical outcome regarding at least one second subject. In one
embodiment 6970, the at least one second subject has not received
the one or more frozen particle compositions (or frozen piercing
implements). In one embodiment 6980, the method further comprises
predicting at least one clinical outcome involving the at least one
second subject, wherein the at least one second subject is a
plurality of people; and segregating subject identifiers associated
with the plurality of people in reference to the predicted at least
one clinical outcome.
[0954] As indicated in FIG. 70, in one embodiment 7010, the one or
more frozen particle compositions (or frozen piercing implements)
include one or more frozen particles including at least one of
hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[0955] In one embodiment 7020, the one or more frozen particle
compositions (or frozen piercing implements) include one or more of
an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 7030, the adhesive agent, therapeutic agent,
reinforcement agent, abrasive, explosive material, or biological
remodeling agent is substantially in the form of at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, oligosaccharide, polysaccharide, glycopeptide, glycolipid,
sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan,
lipid, carbohydrate, metalloprotein, proteoglycan, chromosome, cell
nucleus, acid, base, buffer, protic solvent, aprotic solvent,
nitric oxide, nitric oxide synthase, nitrous oxide, amino acid,
micelle, polymer, bone cement, copolymer, cell receptor, adhesion
molecule, cytokine, chemokine, immunoglobulin, antibody, antigen,
platelet, extracellular matrix, blood, plasma, cell ligand,
zwitterionic material, cationic material, oligonucleotide,
nanotube, or piloxymer.
[0956] In one embodiment 7040, the one or more explosive materials
include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal.
[0957] As indicated in FIG. 71, the at least one adhesive agent
7110 includes one or more of an acrylic polymer or copolymer,
acrylamide polymer or copolymer polymer or copolymer, acrylamide
polymer or copolymer, polyacrylic acid, epoxy, urethane, gum
arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or
gelatin.
[0958] In one embodiment 7120, the one or more reinforcement agents
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
[0959] In one embodiment 7130, the therapeutic agent includes at
least one of an anti-tumor agent, antimicrobial agent, anti-viral
agent, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
[0960] As indicated in FIG. 72, the at least one biological
remodeling agent 7210 includes one or more of a blood cell,
chondrocyte, endothelial cell, hepatocyte, keratinocyte, myocyte,
osteoblast, osteoclast, osteocyte, mesenchymal cell, stem cell,
progenitor cell, or fibroblast. In one embodiment 7220, the at
least one biological remodeling agent includes one or more of
calcium phosphate, albumin, cytokine, pegylated cytokine, bone,
cartilage, globulin, fibrin, thrombin, glutaraldehyde-crosslinked
pericardium, hide powder, hyaluronic acid, hydroxylapatite,
keratin, ligament, nitinol, nucleic acid polymers, polyethylene,
polylethylene glycol, polyethylene glycol diacrylate, polyethylene
terephthalate fiber, polyglycol, polylactate,
polytetrafluoroethylene, polylactic acid, polyglycolic acid,
polycaprolactone, PURAMATRIX.TM. self-assembly peptide hydrogel
fibers, linear aliphatic polyester, tendon, fibrinogen,
hyaluronate, chitin, chitosan, methylcellulose, alginate,
hyaluronic acid, agarose, cellulose, polyaldehyde gluronate, Factor
XIII, Factor XII, silk, nylon, collagen, silicone, polyurethane,
ceramic powder, elastin, pectin, wax, glycosaminoglycan,
poly(.alpha.-hydroxyacid), selectin, glutaraldehyde, hydrophobic
non-glycosylated protein, hydrogel, peptide hydrogel, or gelatin.
In one embodiment 7230, the at least one biological remodeling
agent includes one or more of Type I collagen, Type II collagen,
Type III collagen, Type VII collagen, Type X collagen, elastin
fibers, or soluble elastin. In one embodiment 7240, the at least
one biological remodeling agent is included as part of a carrier
that assists in synthesis or activation of the at least one
biological remodeling agent.
[0961] As indicated in FIG. 73, a system 7300 comprises at least
one computing device 7310; one or more instructions 7340 that when
executed on the at least one computing device cause the at least
one computing device to receive a first input associated with a
first possible dataset, the first possible dataset including data
representative of one or more parameters for administering one or
more frozen particle compositions (or frozen piercing implements).
In one embodiment 7350, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to compare a value
associated with the first possible dataset with a second dataset
including values of at least one predictive parameter for
administering one or more frozen particle compositions (or frozen
piercing implements).
[0962] In one embodiment 7320, the at least one computing device
includes one or more of a desktop computer, workstation computer,
or computing system. In one embodiment 7330, the at least one
computing system includes one or more of a cluster of processors, a
networked computer, a tablet personal computer, a laptop computer,
a mobile device, a mobile telephone, or a personal digital
assistant computer.
[0963] As indicated in FIG. 74, the system further comprises one or
more instructions 7460 that when executed on the at least one
computing device cause the at least one computing device to
determine a graphical illustration of the second possible
dataset.
[0964] In one embodiment 7410, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to determine from
the comparison at least one parameter for administering one or more
frozen particle compositions (or frozen piercing implements). In
one embodiment 7420, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to generate at least
one response based on the determination. In one embodiment 7430,
the system further comprises one or more instructions that when
executed on the at least one computing device cause the at least
one computing device to access the first possible dataset in
response to the first input.
[0965] In one embodiment 7440, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to generate the
first possible dataset in response to the first input.
[0966] In one embodiment 7450, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the first possible dataset.
[0967] As indicated in FIG. 75, a system 7510 comprises at least
one computing device 7520; one or more instructions 7560 that when
executed on the at least one computing device cause the at least
one computing device to receive a first input associated with a
first possible dataset, the first possible dataset including data
representative of one or more characteristics of at least one
biological tissue or organ to be at least partially constructed or
at least partially reconstructed by administering one or more
frozen particle compositions (or frozen piercing implements). In
one embodiment 7570, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to compare a value
associated with the first possible dataset with a second dataset
including values of at least one predictive characteristic of at
least one biological tissue or organ to be at least partially
constructed or at least partially reconstructed by administering
one or more frozen particle compositions (or frozen piercing
implements).
[0968] In one embodiment 7530, the at least one computing device
includes one or more of a desktop computer, workstation computer,
or computing system. In one embodiment 7540, the at least one
computing system includes one or more of a cluster of processors, a
networked computer, a tablet personal computer, a laptop computer,
a mobile device, a mobile telephone, or a personal digital
assistant computer. In one embodiment 7550, the at least one
computing device is configured to communicate with at least one
apparatus for selecting or generating one or more frozen particle
compositions (or frozen piercing implements).
[0969] As indicated in FIG. 76, the system further comprises one or
more instructions 7610, that when executed on the at least one
computing device cause the at least one computing device to
determine a graphical illustration of the second possible dataset.
In one embodiment 7620, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine from
the comparison at least one characteristic of the at least one
biological tissue or organ to be at least partially constructed or
at least partially reconstructed by administering one or more
frozen particle compositions (or frozen piercing implements). In
one embodiment 7630, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to generate at least
one response based on the determination.
[0970] In one embodiment 7640, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to access the first
possible dataset in response to the first input. In one embodiment
7650, the system further comprises one or more instructions that
when executed on the at least one computing device cause the at
least one computing device to generate the first possible dataset
in response to the first input. In one embodiment 7660, the system
further comprises one or more instructions that when executed on
the at least one computing device cause the at least one computing
device to determine a graphical illustration of the first possible
dataset.
[0971] As indicated in FIG. 77, a system 7700 comprises a
signal-bearing medium 7710 bearing one or more instructions 7720
for accepting a first input associated with at least one
characteristic of at least one biological tissue to be at least
partially constructed or at least partially reconstructed by
administering one or more frozen particle compositions (or frozen
piercing implements); one or more instructions 7730 for accepting a
second input associated with at least one characteristic of at
least one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue by
administering one or more frozen particle compositions (or frozen
piercing implements) that include at least one agent; and one or
more instructions 7740 for processing results of the first input
and the second input. In one embodiment 7750, the system further
comprising one or more instructions for displaying results of the
processing.
[0972] In one embodiment 7760, the system further comprises one or
more instructions for transmitting one or more signals that include
information related to the processing results of the first input
and the second input. In one embodiment 7770, the system further
comprises one or more instructions for administering one or more
frozen particle compositions (or frozen piercing implements) that
include at least one agent including: biological remodeling agent,
therapeutic agent, adhesive agent, abrasive, reinforcement agent,
or explosive material. In one embodiment, the system 7780 further
comprises one or more instructions for evaluating the at least one
biological tissue for one or more indicators relating to one or
more of: deposition of at least one agent, tissue formation, or
tissue growth.
[0973] In one embodiment 7790, the signal-bearing medium includes a
computer-readable medium. In one embodiment 7795, the
signal-bearing medium includes a recordable medium. In one
embodiment 7797, the signal-bearing medium includes a
communications medium.
[0974] As indicated in FIG. 78, a computer program product 7800
comprises a signal-bearing medium 7810 bearing one or more
instructions 7820 for accepting a first input associated with at
least one characteristic of at least one biological tissue to be at
least partially constructed or at least partially reconstructed by
administering one or more frozen particle compositions (or frozen
piercing implements); one or more instructions 7830 for accepting a
second input associated with at least one characteristic of at
least one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue by
administering one or more frozen particle compositions (or frozen
piercing implements) that include at least one agent; and one or
more instructions 7840 for processing results of the first input
and the second input.
[0975] In one embodiment 7850, the computer program product further
comprises one or more instructions for displaying results of the
processing. In one embodiment 7860, the computer program product
further comprises one or more instructions for transmitting one or
more signals that include information related to the processing
results of the first input and the second input. In one embodiment
7870, the computer program product further comprises one or more
instructions for administering one or more frozen particle
compositions (or frozen piercing implements) that include at least
one agent including biological remodeling agent, therapeutic agent,
adhesive agent, abrasive, reinforcement agent, or explosive
material.
[0976] In one embodiment 7880, the computer program product further
comprises one or more instructions for evaluating the at least one
biological tissue for one or more indicators relating to one or
more of deposition of at least one agent, tissue formation, or
tissue growth.
[0977] In one embodiment 7890, the signal-bearing medium includes a
computer-readable medium. In one embodiment 7895, the
signal-bearing medium includes a recordable medium. In one
embodiment 7897, the signal-bearing medium includes a
communications medium.
[0978] As indicated in FIG. 79, a system 7900 comprises circuitry
7910 for accepting a first input associated with at least one
characteristic of at least one biological tissue to be at least
partially constructed or at least partially reconstructed by
administering one or more frozen particle compositions (or frozen
piercing implements); circuitry 7920 for accepting a second input
associated with at least one characteristic of at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions (or frozen piercing
implements) that include at least one agent; and circuitry 7930 for
processing results of the first input and the second input. In one
embodiment 7940, the system further comprises circuitry for
displaying results of the processing. In one embodiment 7950, the
system further comprises circuitry for transmitting one or more
signals that include information related to the processing results
of the first input and the second input. In one embodiment 7960,
the system further comprises circuitry for administering one or
more frozen particle compositions (or frozen piercing implements)
that include at least one agent including at least one biological
remodeling agent, therapeutic agent, adhesive agent, abrasive,
reinforcement agent, or explosive material. In one embodiment 7970,
the system further comprises circuitry for evaluating the at least
one biological tissue for one or more indicators relating to one or
more of deposition of at least one agent, tissue formation, or
tissue growth.
[0979] As indicated in FIG. 80, a system 8000 comprises at least at
least one computer program 8010, configured with a
computer-readable medium, for use with at least one computer system
and wherein the computer program includes a plurality of
instructions including but not limited to: one or more instructions
8020 for accepting a first input associated with at least one
characteristic of at least one biological tissue to be at least
partially constructed or at least partially reconstructed by
administering one or more frozen particle compositions (or frozen
piercing implements); one or more instructions 8030 for accepting a
second input associated with at least one characteristic of at
least one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue by
administering one or more frozen particle compositions (or frozen
piercing implements) that include at least one agent; and one or
more instructions 8040 for processing results of the first input
and the second input.
[0980] In one embodiment 8050, the system further comprises one or
more instructions for displaying results of the processing. In one
embodiment 8060, the system further comprises one or more
instructions for transmitting one or more signals that include
information related to the processing results of the first input
and the second input.
[0981] In one embodiment 8070, the system further comprises one or
more instructions for administering one or more frozen particle
compositions (or frozen piercing implements) that include at least
one agent including biological remodeling agent, therapeutic agent,
adhesive agent, abrasive, reinforcement agent, or explosive
material.
[0982] In one embodiment 8080, the system further comprises one or
more instructions for evaluating the at least one biological tissue
for one or more indicators relating to one or more of deposition of
at least one agent, tissue formation, or tissue growth.
[0983] As indicated in FIG. 81, the system further comprises at
least one computing device 8110. In one embodiment 8120, the at
least one computing device is configured to communicate with at
least one printing device, at least one imaging device, or at least
one input device.
[0984] As indicated in FIG. 82, a system 8200 comprises means 8210
for accepting a first input associated with at least one
characteristic of at least one biological tissue to be at least
partially constructed or at least partially reconstructed; means
8220 for accepting a second input associated with at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions (or frozen piercing
implements) including at least one agent; and means 8260 for
processing results of the first input and the second input. In one
embodiment 8230 the at least one agent includes one or more of a
therapeutic agent, adhesive agent, abrasive, reinforcement agent,
explosive material, or biological remodeling agent. In one
embodiment 8240 the administering one or more frozen particle
compositions (or frozen piercing implements) includes administering
the one or more frozen particle compositions (or frozen piercing
implements) to at least one substrate. In one embodiment 8250 the
at least one substrate includes one or more of a cell, tissue,
organ, structure, or device. In one embodiment 8270 means for
processing results of the first input and the second input include
means for electronically processing results of the first input and
the second input. In one embodiment 8280 means for electronically
processing results of the first input and the second input by
utilizing one or more of Gaussian smoothing, scaling, homorphic
filtering, parametric estimation techniques, Boolean operations,
Monte Carlo simulations, wavelet based techniques, mirroring,
smoothing, gradient weighted partial differential equation
smoothing, NURBS, polygonal modeling, splines and patches modeling,
algorithmic execution, logical decision-making, result prediction,
Finite Element Analysis, or modification of a CAD design.
[0985] As indicated in FIG. 83, the first input 8310 includes one
or more values related to the at least one characteristic of at
least one biological tissue. In one embodiment 8320, the first
input includes one or more spatial addresses associated with the at
least one characteristic of at least one biological tissue. In one
embodiment 8330, the first input includes one or more of x, y, or z
coordinates associated with the at least one characteristic of at
least one biological tissue.
[0986] In one embodiment, the at least one characteristic 8340 of
at least one biological tissue to be at least partially constructed
or at least partially reconstructed includes one or more of:
morphological feature, anatomical feature, histological feature,
tissue hierarchical level, scaffold feature, vascular structure
feature, heterogenous tissue feature, mechanical feature,
volumetric feature, geometric feature, volumetric representation,
mechanical feature, deformation, kinematic feature, surface contour
feature, cytometric feature, cell aggregation, cell growth,
cell-cell interaction, cell-tissue interaction, biomimetic design,
cell pattern, cell deposition, organ hierarchical level, tissue
microstructure, cellular microstructure, cell junction feature,
tissue junction feature, cell-tissue classification, hard tissue
classification, soft tissue classification, tumor diagnosis, or
other feature.
[0987] In one embodiment, the at least one characteristic 8350 of
at least one biological tissue includes one or more of cellular
type, cellular function, cellular size, cellular constitution,
cellular architecture, cellular durability, cellular source, tissue
type, tissue constitution, tissue size, tissue shape, tissue
function, tissue architecture, tissue source, tissue durability,
organ type, organ constitution, organ size, organ shape, organ
function, organ architecture, organ source, or organ durability. In
one embodiment, the first input 8360 includes one or more temporal
addresses associated with the at least one characteristic of at
least one biological tissue.
[0988] As indicated in FIG. 84, in one embodiment 8410, the first
input includes one or more values derived from at least one image
of the at least one biological tissue. In one embodiment 8420, the
at least one image includes one or more images acquired by one or
more of optical coherence tomography, computer-assisted tomography
scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray, laser,
holography, x-ray crystallography, electrical-impedance monitoring,
microscopy, spectrometry, flow cytommetry, radioisotope imaging,
thermal imaging, multiphoton calcium-imaging, photography, or in
silico generation.
[0989] In one embodiment 8430, the at least one biological tissue
is located in at least one of in situ, in vitro, in vivo, in utero,
in planta, in silico, or ex vivo. In one embodiment 8440, the at
least one biological tissue is at least partially located in at
least one subject. In one embodiment 8450, the system further
comprises means for accepting a third input associated with at
least one feature of the at least one subject. In one embodiment
8460, the at least one feature of the at least one subject includes
one or more of age, gender, genotype, phenotype, proteomic profile,
or health condition.
[0990] As indicated in FIGS. 85-86, in one embodiment 8510 the
means for processing results of the first input and the second
input include means for determining at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue with one or more frozen particle
compositions (or frozen piercing implements) from one or more
values derived from at least one image of the at least one
biological tissue. In one embodiment 8520, the second input
includes one or more values related to the at least one parameter
of at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions (or frozen piercing
implements) to the at least one substrate. In one embodiment 8530,
the one or more values related to the at least one parameter of
constructing or reconstructing the at least one biological tissue
includes one or more predictive values.
[0991] In one embodiment 8540, the at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue includes one or more of porosity
of the at least one substrate, pore size of the at least one
substrate, interconnectivity of the pores of the at least one
substrate, transport properties of the at least one substrate,
cell-tissue formation of the at least one substrate, mechanical
strength of the at least one substrate, ability for attachment or
distribution of the at least one agent included in the one or more
frozen particle compositions (or frozen piercing implements) to the
at least one substrate, ability for attachment or distribution of
one or more cells or tissues to the at least one substrate,
facilitation of at least one nutrient, or tissue formation or
tissue growth associated with the at least one substrate.
[0992] In one embodiment 8610, the at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue by administering one or more
frozen particle compositions (or frozen piercing implements)
includes one or more of: design of plot or model for administration
of one or more frozen particle compositions (or frozen piercing
implements), constitution of the one or more frozen particle
compositions (or frozen piercing implements), formulation of the
one or more frozen particle compositions (or frozen piercing
implements), size of the one or more frozen particle compositions
(or frozen piercing implements), shape of the one or more frozen
particle compositions (or frozen piercing implements), angle of
administration of the one or more frozen particle compositions (or
frozen piercing implements), velocity of administration of the one
or more frozen particle compositions (or frozen piercing
implements), quantity of frozen particle compositions (or frozen
piercing implements) administered, rate of administration of more
than one frozen particle composition (or frozen piercing
implement), spatial location for administration of one or more
frozen particle compositions (or frozen piercing implements),
temporal location for administration of one or more frozen particle
compositions (or frozen piercing implements), method of
administration of one or more frozen particle compositions (or
frozen piercing implements), timing of administration of one or
more frozen particle compositions (or frozen piercing implements),
modulation of administration of one or more frozen particle
compositions (or frozen piercing implements), deposition of one or
more frozen particle compositions (or frozen piercing implements),
or rate of deposition of at least one agent.
[0993] In one embodiment 8620, the at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue by administering one or more
frozen particle compositions (or frozen piercing implements)
includes at least one parameter relating to at least partially
ablating or at least partially abrading one or more surfaces of the
at least one biological tissue with the one or more frozen particle
compositions (or frozen piercing implements).
[0994] In one embodiment 8630, the at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue by administering one or more
frozen particle compositions (or frozen piercing implements)
includes at least one parameter relating to administering at least
one of a therapeutic agent, adhesive agent, biological remodeling
agent, reinforcement agent, abrasive, or explosive material with
the one or more frozen particle compositions (or frozen piercing
implements).
[0995] In one embodiment 8640, the spatial location for
administration of one or more frozen particle compositions (or
frozen piercing implements) includes one or more of x, y, or z
coordinates. In one embodiment 8650, the means for processing
results include means for comparing at least one value related to
the first input associated with the at least one characteristic of
at least one biological tissue to be at least partially constructed
or at least partially reconstructed with at least one value related
to at least one image of a target biological tissue. In one
embodiment 8660, the image of a target biological tissue includes
an image of a similar biological tissue, or an image of a
dissimilar biological tissue.
[0996] As indicated in FIG. 87, the means 8710 for processing
results include means for comparing at least one value related to
the second input associated with the at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue with at least one value related
to another administration of one or more frozen particle
compositions (or frozen piercing implements). In one embodiment
8720, the means for processing results include means for
determining one or more differences in at least one value related
to the first input and at least one value related to at least one
image of the at least one biological tissue or a similar biological
tissue. In one embodiment 8730, the means for processing results
include means for determining one or more differences in at least
one value related to the second input associated with the at least
one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue and at
least one value related to another administration of one or more
frozen particle compositions (or frozen piercing implements) to the
at least one substrate.
[0997] In one embodiment 8740, the means for processing results
include means for generating one or more protocols for
administering the one or more frozen particle compositions (or
frozen piercing implements). In one embodiment 8750, the means for
processing results include generating one or more blueprints for
administering the one or more frozen particle compositions (or
frozen piercing implements). In one embodiment 8760, the one or
more blueprints include at least one of a two-dimensional plot or a
three-dimensional model. In one embodiment 8770, the one or more
blueprints include at least one representation of at least one of
organ anatomy, morphology, tissue heterogeneity, scale of vascular
system, geometry, internal architecture of an organ or tissue,
internal or external boundary distinction of a tissue or organ,
topology, or tomography.
[0998] As indicated in FIG. 88, the means for processing results
include: means for comparing one or more values related to the one
or more characteristics of the at least one biological tissue that
are determined at two or more different times to obtain one or more
characteristic comparisons; means for comparing one or more values
related to the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue at two or more different times to obtain one or
more parameter comparisons; means for comparing the one or more
characteristic comparisons with the one or more parameter
comparisons to obtain one or more
characteristic-characteristic/parameter-parameter comparisons; and
means for comparing the one or more
characteristic-characteristic/parameter-parameter comparisons to
one or more substantially similar results obtained for one or more
other at least partially constructed or at least partially
reconstructed biological tissues. In one embodiment 8820, the
administering one or more frozen particle compositions (or frozen
piercing implements) includes depositing the at least one agent on
the at least one substrate.
[0999] As indicated in FIG. 89, the system further comprises means
8910 for displaying results of the processing. In one embodiment
8920, the means for displaying the results of the processing
include means for displaying the results on one or more active
displays. In one embodiment 8930, the means for displaying results
of the processing include means for displaying the results on one
or more passive displays. In one embodiment 8940, the means for
displaying results of the processing includes means for displaying
the results of the processing in at least one of numeric format,
graphical format, or audio format.
[1000] In one embodiment 8950, the means for displaying results of
the processing include means for displaying a comparison of at
least one biological tissue that has been at least partially
constructed or at least partially reconstructed. In one embodiment
8960, the means for displaying results of the processing include
means for displaying a comparison of at least one subject with one
or more other subjects. In one embodiment 8970, the means for
displaying results of the processing include means for displaying
one or more differences in the comparison of at least one value
related to the first input and at least one value related to at
least one image of a biological tissue. In one embodiment 8980, the
means for displaying results of the processing include means for
displaying one or more differences in the comparison of at least
one value related to the second input and at least one value
related to another administration of one or more frozen particle
compositions (or frozen piercing implements).
[1001] As indicated in FIG. 90, the system further comprises means
9010 for transmitting one or more signals that include information
related to the processing results of the first input and the second
input. In one embodiment 9020, the means for transmitting one or
more signals include means for transmitting one or more signals
associated with selection of one or more frozen particle
compositions (or frozen piercing implements) for administration. In
one embodiment 9030, the means for transmitting one or more signals
include means for transmitting one or more signals associated with
selection of one or more of a biological remodeling agent, adhesive
agent, abrasive, therapeutic agent, reinforcement agent, or
explosive material associated with the one or more frozen particle
compositions (or frozen piercing implements). In one embodiment
9040, the means for transmitting one or more signals include means
for transmitting one or more signals associated with comparing the
information related to the processing results of the first input
and the second input.
[1002] As indicated in FIG. 91, the one or more frozen particle
compositions (or frozen piercing implements) 9110 include one or
more frozen particles including at least one of: hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1003] In one embodiment 9120, the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 9130, at least one of the adhesive agent,
therapeutic agent, reinforcement agent, abrasive, explosive
material, or biological remodeling agent is substantially in the
form of at least one of an organic or inorganic small molecule,
clathrate or caged compound, protocell, coacervate, microsphere,
Janus particle, proteinoid, laminate, helical rod, liposome,
macroscopic tube, niosome, sphingosome, toroid, vesicular tube,
vesicle, small unilamellar vesicle, large unilamellar vesicle,
large multilamellar vesicle, multivesicular vesicle, lipid layer,
lipid bilayer, micelle, organelle, cell, membrane, nucleic acid,
peptide, polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
[1004] As indicated in FIG. 92, the one or more explosive materials
9210 include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal. In one embodiment 9220, the at least one adhesive
agent includes one or more of an acrylic polymer or copolymer,
acrylamide polymer or copolymer polymer or copolymer, acrylamide
polymer or copolymer, polyacrylic acid, epoxy, urethane, gum
arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or
gelatin.
[1005] In at least one embodiment 9230, the one or more
reinforcement agents include one or more of polyaramid, vinylester
matrix, metal, ceramic, fiberglass, cellulose, broad carbide,
aromatic polyamide, nylon, silk, rayon, acetate, modacrylic,
olefin, acrylic, polyester, aromatic polyester, poly-lactic acid,
vinyon, saran, spandex, vinalon, aromatic nylon, vinylidene
chloride, modal, polybenzimidazole, sulfur, lyocell, orlon, zylon,
high-performance polyethylene, polypyridobenzimidazole, vectran,
acrylonitrile rubber, glass, copper, iron, steel, sodium,
potassium, calcium, zinc, manganese, carbon, magnesium, silicon,
silica, frozen hydrogen oxide ice, plant matter, animal matter, or
mineral matter.
[1006] As indicated in FIG. 93, the therapeutic agent 9310 includes
at least one of an anti-tumor agent, antimicrobial agent,
anti-viral agent, analgesic, antiseptic, anesthetic, diagnostic
agent, anti-inflammatory agent, vaccine, cell growth inhibitor,
cell growth promoter, immunogen, antigen, radioactive agent,
apoptosis promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
[1007] In one embodiment 9320 the at least one biological
remodeling agent includes one or more of a blood cell, chondrocyte,
endothelial cell, hepatocyte, keratinocyte, myocyte, osteoblast,
osteoclast, osteocyte, mesenchymal cell, stem cell, progenitor
cell, or fibroblast. In one embodiment 9330, the at least one
biological remodeling agent includes one or more of calcium
phosphate, albumin, cytokine, pegylated cytokine, bone, cartilage,
globulin, fibrin, thrombin, glutaraldehyde-crosslinked pericardium,
hide powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 9340, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin. In one
embodiment 9350, the at least one biological remodeling agent is
included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
[1008] As indicated in FIGS. 94-96, a system 9400 comprises means
9410 for accepting input associated with at least one parameter of
at least partially constructing or at least partially
reconstructing at least one biological tissue by administering one
or more frozen particle compositions (or frozen piercing
implements); means 9420 for administering one or more frozen
particle compositions (or frozen piercing implements) including at
least one agent; wherein 9430 the at least one agent includes one
or more of a biological remodeling agent, therapeutic agent,
reinforcement agent, explosive material, abrasive, or adhesive
agent; means 9440 for evaluating the at least one biological tissue
for one or more indicators related to deposition of at least one
agent, tissue formation, or tissue growth; and means 9610 for
transmitting one or more signals that include information related
to the accepting input and information related to the evaluating
the at least one biological tissue.
[1009] In one embodiment 9450, the means for evaluating at least
one biological tissue for one or more indicators includes
evaluating at least one of an assay, image, or gross assessment of
the at least one biological tissue prior to, during, or subsequent
to at least one administration of the one or more frozen particle
compositions (or frozen piercing implements). In one embodiment
9460, the assay includes at least one technique that includes
spectroscopy, microscopy, electrochemical detection, polynucleotide
detection, histological examination, biopsy analysis, fluorescence
resonance energy transfer, electron transfer, enzyme assay,
electrical conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay.
[1010] In one embodiment 9520, the image includes at least one
image acquired by one or more of optical coherence tomography,
computer-assisted tomography scan, computed tomography, magnetic
resonance imaging, positron-emission tomography scan, ultrasound,
x-ray, x-ray crystallography, laser, holography,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, multiphoton
calcium-imaging, photography, or in silico generation. In one
embodiment 9530, the one or more indicators of tissue formation or
growth include at least one of cell migration, cell attachment,
cell retention, cell differentiation, cell proliferation,
apoptosis, diffusion of materials, angiogenesis, nucleic acid
expression, protein translation, protein modification, carbohydrate
production, carbohydrate secretion, fat production, fat secretion,
or protein secretion.
[1011] In one embodiment 9540, the input associated with at least
one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue by
administering one or more frozen particle compositions (or frozen
piercing implements) includes one or more of: constitution of the
one or more frozen particle compositions (or frozen piercing
implements), formulation of the one or more frozen particle
compositions (or frozen piercing implements), size of the one or
more frozen particle compositions (or frozen piercing implements),
shape of the one or more frozen particle compositions (or frozen
piercing implements), angle of administration of the one or more
frozen particle compositions (or frozen piercing implements),
velocity of administration of the one or more frozen particle
compositions (or frozen piercing implements), quantity of frozen
particle compositions (or frozen piercing implements) administered,
rate of administration of more than one frozen particle composition
(or frozen piercing implement), spatial location for administration
of one or more frozen particle compositions (or frozen piercing
implements), temporal location for administration of one or more
frozen particle compositions (or frozen piercing implements),
method of administration of one or more frozen particle
compositions (or frozen piercing implements), timing of
administration of one or more frozen particle compositions (or
frozen piercing implements), modulation of administration of one or
more frozen particle compositions (or frozen piercing implements),
deposition of one or more frozen particle compositions (or frozen
piercing implements), or rate of deposition of at least one
agent.
[1012] In one embodiment 9620, the means for transmitting one or
more signals include means for transmitting one or more signals
associated with selection of one or more frozen particle
compositions for administration. In one embodiment 9630, the means
for transmitting one or more signals include means for transmitting
one or more signals associated with selection of one or more of a
biological remodeling agent, adhesive agent, abrasive, therapeutic
agent, reinforcement agent, or explosive material associated with
the one or more frozen particle compositions(or frozen piercing
implements). In one embodiment 9640, the means for administering
one or more frozen particle compositions (or frozen piercing
implements) include means for administering the one or more frozen
particle compositions (or frozen piercing implements) to at least
one substrate. In one embodiment 9650, the at least one substrate
includes one or more of a cell, tissue, organ, structure, or
device. In one embodiment 9660, the one or more frozen particle
compositions (or frozen piercing implements) include one or more
frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1013] As indicated in FIG. 97, the at least one agent 9710
includes one or more of an adhesive agent, therapeutic agent,
reinforcement agent, abrasive, explosive material, or biological
remodeling agent. In one embodiment 9720, the adhesive agent,
therapeutic agent, reinforcement agent, abrasive, explosive
material, or biological remodeling agent is substantially in the
form of at least one of an organic or inorganic small molecule,
clathrate or caged compound, protocell, coacervate, microsphere,
Janus particle, proteinoid, laminate, helical rod, liposome,
macroscopic tube, niosome, sphingosome, toroid, vesicular tube,
vesicle, small unilamellar vesicle, large unilamellar vesicle,
large multilamellar vesicle, multivesicular vesicle, lipid layer,
lipid bilayer, micelle, organelle, cell, membrane, nucleic acid,
peptide, polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
[1014] In one embodiment 9730, the one or more explosive materials
include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal. In one embodiment 9740, the at least one adhesive
agent includes one or more of an acrylic polymer or copolymer,
acrylamide polymer or copolymer polymer or copolymer, acrylamide
polymer or copolymer, polyacrylic acid, epoxy, urethane, gum
arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or
gelatin.
[1015] As indicated in FIG. 98, the one or more reinforcement
agents 9810 include one or more of polyaramid, vinylester matrix,
metal, ceramic, fiberglass, cellulose, broad carbide, aromatic
polyamide, nylon, silk, rayon, acetate, modacrylic, olefin,
acrylic, polyester, aromatic polyester, poly-lactic acid, vinyon,
saran, spandex, vinalon, aromatic nylon, vinylidene chloride,
modal, polybenzimidazole, sulfur, lyocell, orlon, zylon,
high-performance polyethylene, polypyridobenzimidazole, vectran,
acrylonitrile rubber, glass, copper, iron, steel, sodium,
potassium, calcium, zinc, manganese, carbon, magnesium, silicon,
silica, frozen hydrogen oxide ice, plant matter, animal matter, or
mineral matter.
[1016] In one embodiment 9820, the therapeutic agent includes at
least one of an anti-tumor agent, antimicrobial agent, anti-viral
agent, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof. In one embodiment 9830, the at least
one biological remodeling agent includes one or more of a blood
cell, chondrocyte, endothelial cell, hepatocyte, keratinocyte,
myocyte, osteoblast, osteoclast, osteocyte, mesenchymal cell, stem
cell, progenitor cell, or fibroblast.
[1017] In one embodiment 9840, the at least one biological
remodeling agent includes one or more of calcium phosphate,
albumin, cytokine, pegylated cytokine, bone, cartilage, globulin,
fibrin, thrombin, glutaraldehyde-crosslinked pericardium, hide
powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin.
[1018] In one embodiment 9850, the at least one biological
remodeling agent includes one or more of Type I collagen, Type II
collagen, Type III collagen, Type VII collagen, Type X collagen,
elastin fibers, or soluble elastin.
[1019] As indicated in FIG. 99, a system 9900 comprises means 9910
for receiving one or more signals that include information related
to accepting input associated with at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue by administering one or more
frozen particle compositions (or frozen piercing implements); means
9920 for receiving one or more signals that include information
related to evaluating the at least one biological tissue for one or
more indicators of tissue formation or growth; and means for 9930
processing the information related to the input associated with at
least one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue and the
information related to the evaluating the at least one biological
tissue. In one embodiment 9940, the evaluating at least one
biological tissue for one or more indicators includes evaluating at
least one of an assay, image, or gross assessment of the at least
one biological tissue prior to, during, or subsequent to at least
one administration of one or more frozen particle compositions (or
frozen piercing implements).
[1020] In one embodiment 9950, the assay includes at least one
technique that includes spectroscopy, microscopy, electrochemical
detection, polynucleotide detection, histological examination,
biopsy analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment 9960, the image includes at
least one image acquired by one or more of optical coherence
tomography, computer-assisted tomography scan, computed tomography,
laser, holography, x-ray crystallography, magnetic resonance
imaging, positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, multiphoton
calcium-imaging, photography, or in silico generation.
[1021] As indicated in FIG. 100, the one or more indicators 10010
of tissue formation or growth include at least one of: cell
migration, cell attachment, cell retention, cell differentiation,
cell proliferation, apoptosis, diffusion of materials,
angiogenesis, nucleic acid expression, protein translation, protein
modification, carbohydrate production, carbohydrate secretion, fat
production, fat secretion, or protein secretion.
[1022] In one embodiment 10020, the input associated with at least
one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue
includes one or more of: constitution of the one or more frozen
particle compositions (or frozen piercing implements), formulation
of the one or more frozen particle compositions (or frozen piercing
implements), size of the one or more frozen particle compositions
(or frozen piercing implements), shape of the one or more frozen
particle compositions (or frozen piercing implements), angle of
administration of the one or more frozen particle compositions (or
frozen piercing implements), velocity of administration of the one
or more frozen particle compositions (or frozen piercing
implements), quantity of frozen particle compositions (or frozen
piercing implements) administered, rate of administration of more
than one frozen particle composition (or frozen piercing
implement), spatial location for administration of one or more
frozen particle compositions (or frozen piercing implements),
temporal location for administration of one or more frozen particle
compositions (or frozen piercing implements), method of
administration of one or more frozen particle compositions (or
frozen piercing implements), timing of administration of one or
more frozen particle compositions (or frozen piercing implements),
modulation of administration of one or more frozen particle
compositions (or frozen piercing implements), deposition of one or
more frozen particle compositions (or frozen piercing implements),
or rate of deposition of at least one agent.
[1023] In one embodiment 10030, the means for receiving one or more
signals include means for receiving one or more signals associated
with selection of one or more frozen particle compositions (or
frozen piercing implements) for administration. In one embodiment
10040, the means for receiving one or more signals include means
for receiving one or more signals associated with the selection of
at least one of a biological remodeling agent, adhesive agent,
abrasive, therapeutic agent, reinforcement agent, or explosive
material associated with the one or more frozen particle
compositions (or frozen piercing implements).
[1024] As indicated in FIG. 101, in one embodiment 10110, the means
for administering one or more frozen particle compositions (or
frozen piercing implements) include means for administering the one
or more frozen particle compositions (or frozen piercing
implements) to at least one substrate. In one embodiment 10120, the
at least one substrate includes one or more of a cell, tissue,
organ, structure, or device. In one embodiment 10130, the one or
more frozen particle compositions (or frozen piercing implements)
include one or more frozen particles including at least one of
hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1025] In one embodiment 10140, the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 10150, the adhesive agent, therapeutic
agent, reinforcement agent, abrasive, explosive material, or
biological remodeling agent is substantially in the form of at
least one of an organic or inorganic small molecule, clathrate or
caged compound, protocell, coacervate, microsphere, Janus particle,
proteinoid, laminate, helical rod, liposome, macroscopic tube,
niosome, sphingosome, toroid, vesicular tube, vesicle, small
unilamellar vesicle, large unilamellar vesicle, large multilamellar
vesicle, multivesicular vesicle, lipid layer, lipid bilayer,
micelle, organelle, cell, membrane, nucleic acid, peptide,
polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
[1026] As indicated in FIG. 102, the one or more explosive
materials 10210 include at least one of a carbonate, carbon
dioxide, nitroglycerine, acid, base, epoxy, acrylic polymer or
copolymer, acrylamide polymer or copolymer, urethane,
hypoxyapatite, or reactive metal. In one embodiment 10220, the at
least one adhesive agent includes one or more of an acrylic polymer
or copolymer, acrylamide polymer or copolymer polymer or copolymer,
acrylamide polymer or copolymer, polyacrylic acid, epoxy, urethane,
gum arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or gelatin.
In one embodiment 10230, the one or more reinforcement agents
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
[1027] In one embodiment 10240, the therapeutic agent includes at
least one of an anti-tumor agent, antimicrobial agent, anti-viral
agent, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
[1028] As indicated in FIG. 103, in one embodiment 10310, the at
least one biological remodeling agent includes one or more of a
blood cell, chondrocyte, endothelial cell, hepatocyte,
keratinocyte, myocyte, osteoblast, osteoclast, osteocyte,
mesenchymal cell, stem cell, progenitor cell, or fibroblast. In one
embodiment 10320, the at least one biological remodeling agent
includes one or more of calcium phosphate, albumin, cytokine,
pegylated cytokine, bone, cartilage, globulin, fibrin, thrombin,
glutaraldehyde-crosslinked pericardium, hide powder, hyaluronic
acid, hydroxylapatite, keratin, ligament, nitinol, nucleic acid
polymers, polyethylene, polylethylene glycol, polyethylene glycol
diacrylate, polyethylene terephthalate fiber, polyglycol,
polylactate, polytetrafluoroethylene, polylactic acid, polyglycolic
acid, polycaprolactone, PURAMATRIX.TM. self-assembly peptide
hydrogel fibers, linear aliphatic polyester, tendon, fibrinogen,
hyaluronate, chitin, chitosan, methylcellulose, alginate,
hyaluronic acid, agarose, cellulose, polyaldehyde gluronate, Factor
XIII, Factor XII, silk, nylon, collagen, silicone, polyurethane,
ceramic powder, elastin, pectin, wax, glycosaminoglycan,
poly(.alpha.-hydroxyacid), selectin, glutaraldehyde, hydrophobic
non-glycosylated protein, hydrogel, peptide hydrogel, or gelatin.
In one embodiment 10330, the at least one biological remodeling
agent includes one or more of Type I collagen, Type II collagen,
Type III collagen, Type VII collagen, Type X collagen, elastin
fibers, or soluble elastin.
[1029] In one embodiment 10340, the at least one biological
remodeling agent is included as part of a carrier that assists in
synthesis or activation of the at least one biological remodeling
agent.
[1030] As indicated in FIG. 104, a system 10400 comprises means for
comparing information 10410 regarding at least one parameter for at
least partially constructing or at least partially reconstructing
at least one biological tissue of a subject by administering one or
more frozen particle compositions (or frozen piercing implements)
to the at least one subject and information regarding at least one
clinical outcome following receipt by the at least one subject of
one or more frozen particle compositions (or frozen piercing
implements); and means for providing output information 10420. In
one embodiment 10430, the output information is based on the
comparison. In one embodiment 10440, the system further comprises
means for determining at least one statistical correlation. In one
embodiment 10450, the system further comprises means for counting
the occurrence of at least one clinical outcome. In one embodiment
10460, the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject includes information
regarding quantity of cells or tissue at least partially
constructed or at least partially reconstructed. In one embodiment
10470, the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject includes information
regarding at least one cellular or tissue source. In one embodiment
10480, the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject includes information
regarding at least one abnormal cellular or tissue source. In one
embodiment 10490, the information regarding at least one parameter
of at least partially constructing or at least partially
reconstructing at least one biological tissue of a subject includes
information regarding at least one type of cell or tissue.
[1031] As indicated in FIG. 105, the at least one agent 10510
includes at least one agent including at least one adhesive agent,
abrasive, reinforcement agent, therapeutic agent, biological
remodeling agent, or explosive material. In one embodiment 10520,
the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject includes information
regarding at least one dimension of at least one agent deposited.
In one embodiment 10530, the information regarding at least one
parameter of at least partially constructing or at least partially
reconstructing at least one biological tissue of at least one
subject includes information regarding at least one dimension of at
least one depth, width, or breadth of cellular, tissue, or other
material removal or destruction. In one embodiment 10540, the
information regarding at least one clinical outcome following
receipt by the at least one subject of one or more frozen particle
compositions (or frozen piercing implements) includes information
regarding two or more subjects with one or more common
attributes.
[1032] In one embodiment 10550, the one or more common attributes
include one or more of genetic attributes, mental attributes,
proteomic attributes, phenotypic attributes, or psychological
attributes. In one embodiment 10560, the one or more common
attributes include one or more of height, weight, medical
diagnosis, familial background, results on one or more medical
tests, ethnic background, body mass index, age, presence or absence
of at least one disease or condition, species, ethnicity, race,
allergies, gender, thickness of tissue, blood vessel condition,
hair or fur condition, skin condition, tissue condition, muscle
condition, organ condition, nerve condition, brain condition,
presence or absence of at least one biological, chemical, or
therapeutic agent in the subject, pregnancy status, lactation
status, genetic profile, proteomic profile, partial or whole
genetic sequence, partial or whole proteomic sequence, medical
condition, medical history, or blood condition.
[1033] As indicated in FIG. 106, the output information 10610
includes at least one of a response signal, comparison code,
comparison plot, diagnostic code, treatment code, test code, code
indicative of at least one treatment received, code indicative of
at least one prescribed treatment step, code indicative of at least
one vaccination administered, code indicative of at least one
therapeutic agent administered, code indicative of at least one
diagnostic agent administered, code indicative of at least one
interaction of an administered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispertion or location of at least one administered agent; code
indicative of at least one detection material administered; code
indicative of the depth of penetration of an administered agent,
code indicative of the depth of deposition of an administered
agent, or a code indicative of the condition of at least one
location of an administered frozen particle composition (or frozen
piercing implement).
[1034] In one embodiment 10620, receipt by the at least one subject
of one or more frozen particle compositions (or frozen piercing
implements) is pursuant to at least one clinical trial. In one
embodiment 10630, the method further comprises determining at least
one correlation before the administration of the one or more frozen
particle compositions (or frozen piercing implements) to the at
least one subject.
[1035] In one embodiment 10640, the method further comprises
creating at least one inclusion criterion and at least one
exclusion criterion for a clinical trial involving the one or more
frozen particle compositions (or frozen piercing implements). In
one embodiment 10650, the method further comprises suggesting the
inclusion of one or more of the at least one subject in at least
one clinical trial. In one embodiment 10660, the method further
comprises suggesting the exclusion of one or more of the at least
one subject in at least one clinical trial.
[1036] As indicated in FIG. 107, the system further comprises means
for using one or more of the at least one correlation 10710 to
predict at least one clinical outcome regarding at least one second
subject. In one embodiment 10720, the at least one second subject
has not received the one or more frozen particle compositions (or
frozen piercing implements). In one embodiment 10730, the system
further comprises means for predicting at least one clinical
outcome involving the at least one second subject, wherein the at
least one second subject is a plurality of people; and means for
segregating subject identifiers associated with the plurality of
people in reference to the predicted at least one clinical outcome.
In one embodiment 10740, the system further comprises means for
determining the eligibility of the at least one second subject for
the at least one clinical trial.
[1037] In one embodiment 10750, the one or more frozen particle
compositions (or frozen piercing implements) include one or more
frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1038] As indicated in FIG. 108, the at least one agent 10810
includes one or more of an adhesive agent, therapeutic agent,
reinforcement agent, abrasive, explosive material, or biological
remodeling agent. In one embodiment 10820, the adhesive agent,
therapeutic agent, reinforcement agent, abrasive, explosive
material, or biological remodeling agent is substantially in the
form of at least one of an organic or inorganic small molecule,
clathrate or caged compound, protocell, coacervate, microsphere,
Janus particle, proteinoid, laminate, helical rod, liposome,
macroscopic tube, niosome, sphingosome, toroid, vesicular tube,
vesicle, small unilamellar vesicle, large unilamellar vesicle,
large multilamellar vesicle, multivesicular vesicle, lipid layer,
lipid bilayer, micelle, organelle, cell, membrane, nucleic acid,
peptide, polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer. In one
embodiment 10830, the one or more explosive materials include at
least one of a carbonate, carbon dioxide, nitroglycerine, acid,
base, epoxy, acrylic polymer or copolymer, acrylamide polymer or
copolymer, urethane, hypoxyapatite, or reactive metal. In one
embodiment 10840, the at least one adhesive agent includes one or
more of an acrylic polymer or copolymer, acrylamide polymer or
copolymer polymer or copolymer, acrylamide polymer or copolymer,
polyacrylic acid, epoxy, urethane, gum arabic, polyester,
polyhydroxyalkanoate, poly(L-lactic acid), polyglycolide,
polylactic acid, polyether, polyol, polyvinylpyrrolidone,
pyroxylin, polymethylacrylate-isobutene-monoisopropylmaleate,
siloxane polymer, polylactic-co-glycolic-acid,
poly-3-hydroxybutyrate, poly-4-hydroxybutyrate,
polyhydroxyvalerate, polydydroxyhexanoate, polydyroxyoctanoate,
polycaprolactone, poly (e-caprolactone), sialyl Lewis.sup.x, heme
group, hemoglobin, healon, carboxymethylcellulose, hydroxyapatite,
silicone, cadherin, integrin, hydroxyapatite, polyelectrolyte,
maleic polyelectrolyte, cellulose, resilin, cyanoacrylate,
isocyanate, 2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate,
n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl
2-cyanoacrylate, polyisohexylcyanoacrylate, fibrin, thrombin,
fibrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk,
nylon, collagen, glycosaminoglycan, selectin, polyurethane,
methacrylate, or polysulfide, polyanhydride, polydioxanone,
poly-p-dioxanone, silicone, albumin, glutaraldehyde, polyethylene
glycol, or gelatin.
[1039] As indicated in FIG. 109, the one or more reinforcement
agents 10910 include one or more of polyaramid, vinylester matrix,
metal, ceramic, fiberglass, cellulose, broad carbide, aromatic
polyamide, nylon, silk, rayon, acetate, modacrylic, olefin,
acrylic, polyester, aromatic polyester, poly-lactic acid, vinyon,
saran, spandex, vinalon, aromatic nylon, vinylidene chloride,
modal, polybenzimidazole, sulfur, lyocell, orlon, zylon,
high-performance polyethylene, polypyridobenzimidazole, vectran,
acrylonitrile rubber, glass, copper, iron, steel, sodium,
potassium, calcium, zinc, manganese, carbon, magnesium, silicon,
silica, frozen hydrogen oxide ice, plant matter, animal matter, or
mineral matter.
[1040] In one embodiment 10920, the therapeutic agent includes at
least one of an anti-tumor agent, antimicrobial agent, anti-viral
agent, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof. In one embodiment 10930, the at
least one biological remodeling agent includes one or more of a
blood cell, chondrocyte, endothelial cell, hepatocyte,
keratinocyte, myocyte, osteoblast, osteoclast, osteocyte,
mesenchymal cell, stem cell, progenitor cell, or fibroblast.
[1041] As indicated in FIG. 110, the at least one biological
remodeling agent 11010 includes one or more of calcium phosphate,
albumin, cytokine, pegylated cytokine, bone, cartilage, globulin,
fibrin, thrombin, glutaraldehyde-crosslinked pericardium, hide
powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 11020, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin. In one
embodiment 11030, the at least one biological remodeling agent is
included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
[1042] As indicated in FIGS. 111-113, one embodiment relates to a
system 11100 comprising means for predicting a clinical outcome of
one or more frozen particle composition (or frozen piercing
implement) treatments for at least one first subject, including
means 11120 for determining a similarity or a dissimilarity in
information regarding at least one parameter for at least partially
constructing or at least partially reconstructing at least one
biological tissue of at least one first subject by administering
one or more frozen particle compositions (or frozen piercing
implements) to the at least one first subject with information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one second subject; wherein 11130 the at least one
second subject attained a clinical outcome following receipt of the
one or more frozen particle compositions (or frozen piercing
implements); and 11140 means for providing output information. In
one embodiment 11150, the output information is based on the
determination.
[1043] In one embodiment 11160, the information regarding at least
one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of at least
one second subject includes information regarding quantity of cells
or tissue at least partially constructed or at least partially
reconstructed. In one embodiment 11170, the information regarding
at least one parameter of at least partially constructing or at
least partially reconstructing at least one biological tissue of at
least one first subject includes information regarding at least one
cellular or tissue source. In one embodiment 11180, the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one first subject includes information regarding at
least one abnormal cellular or tissue source.
[1044] As indicated in FIG. 112, in one embodiment 11210, the
information regarding at least one parameter of at least partially
constructing or at least partially reconstructing at least one
biological tissue of at least one first subject includes
information regarding at least one type of cell or tissue. In one
embodiment 11220 the information regarding at least one parameter
of at least partially constructing or at least partially
reconstructing at least one biological tissue of at least one
second subject includes information regarding at least one type of
cell or tissue. In one embodiment 11230 the at least one agent
includes one or more of an adhesive agent, abrasive, reinforcement
agent, therapeutic agent, biological remodeling agent, or explosive
material. In one embodiment 11240 the information regarding at
least one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of at least
one first subject includes information regarding at least one
dimension of at least one agent deposited. In one embodiment 11250
the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of at least one second subject includes
information regarding at least one dimension of at least one agent
deposited. In one embodiment 11260, the information regarding at
least one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of at least
one second subject includes information regarding at least one
dimension of at least one depth, width, or breadth of cellular,
tissue, or other material removal or destruction. In one embodiment
11270, the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of at least one first subject includes
information regarding at least one dimension of at least one depth,
width, or breadth of cellular, tissue, or other material removal or
destruction.
[1045] As indicated in FIG. 113, in one embodiment 11310, the
information regarding at least one clinical outcome following
receipt by the at least one second subject of one or more frozen
particle compositions (or frozen piercing implements) includes
information regarding two or more subjects with one or more common
attributes. In one embodiment 11320, the one or more common
attributes include but are not limited to genetic attributes,
mental attributes, proteomic attributes, phenotypic attributes, or
psychological attributes. In one embodiment 11330, the one or more
common attributes include at least one of height; weight; medical
diagnosis; familial background; results on one or more medical
tests; ethnic background; body mass index; age; presence or absence
of at least one disease or condition; species; ethnicity; race;
allergies; gender; thickness of epidermis; thickness of dermis;
thickness of stratum corneum; keratin deposition; collagen
deposition; blood vessel condition; skin condition; hair or fur
condition; muscle condition; tissue condition; organ condition;
nerve condition; brain condition; presence or absence of at least
one biological, chemical, or therapeutic agent in the subject;
pregnancy status; lactation status; medical history; genetic
profile; proteomic profile; partial or whole genetic sequence;
partial or whole proteomic sequence; lymph condition, medical
history, or blood condition.
[1046] In one embodiment 11340, the output information includes at
least one of a response signal, a comparison code, a comparison
plot, a diagnostic code, a treatment code, a test code, a code
indicative of at least one treatment received, a code indicative of
at least one prescribed treatment step, a code indicative of at
least one vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of a
delivered or administered frozen particle composition (or frozen
piercing implement) 2700.
[1047] As indicated in FIG. 114, in one embodiment 11410, receipt
by the at least one second subject of one or more frozen particle
compositions (or frozen piercing implements) is pursuant to at
least one clinical trial. In one embodiment 11420, the system
further comprises means for determining at least one correlation
before the administration of the one or more frozen particle
compositions (or frozen piercing implements) to the at least one
first subject. In one embodiment 11430, the system further
comprises means for creating at least one inclusion criterion and
at least one exclusion criterion for a clinical trial involving the
one or more frozen particle compositions (or frozen piercing
implements). In one embodiment 11440, the system further comprises
means for suggesting the inclusion of one or more of the at least
one first subject in at least one clinical trial.
[1048] In one embodiment 11450, the system further comprises means
for suggesting the exclusion of one or more of the at least one
first subject in at least one clinical trial. In one embodiment
11460, the system further comprises means for using one or more of
the at least one first subject in at least one clinical trial. In
one embodiment 11470, the at least one second subject has not
received the one or more frozen particle compositions (or frozen
piercing implements). In one embodiment 11480, the system further
comprises means for predicting at least one clinical outcome
involving the at least one second subject, wherein the at least one
second subject is a plurality of people; and means for segregating
subject identifiers associated with the plurality of people in
reference to the predicted at least one clinical outcome.
[1049] As indicated in FIG. 115, in one embodiment 11510, the one
or more frozen particle compositions (or frozen piercing
implements) include at least one of hydrogen oxide, nitrogen,
oxygen, air, helium, neon, argon, xenon, chlorine, bromine, carbon
dioxide, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl
formamide, dioxane, tetrahydrofuran, acetronitrile, acetic acid,
n-butanol, isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, standard saline citrate, methane, toluene, chloroform,
polyethylene glycol, acetic acid, Ringer's solution, lactated
Ringer's solution, Hartmann's solution, acetated Ringer's solution,
phosphate buffered solution, TRIS-buffered saline solution, Hank's
balanced salt solution, Earle's balanced salt solution, standard
saline citrate, HEPES-buffered saline, dextrose, glucose, or
diethyl ether.
[1050] In one embodiment 11520, the one or more frozen particle
compositions (or frozen piercing implements) include one or more of
an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent.
[1051] In one embodiment 11530, the adhesive agent, therapeutic
agent, reinforcement agent, abrasive, explosive material, or
biological remodeling agent includes at least one of an organic or
inorganic small molecule, clathrate or caged compound, protocell,
coacervate, microsphere, Janus particle, proteinoid, laminate,
helical rod, liposome, macroscopic tube, niosome, sphingosome,
toroid, vesicular tube, vesicle, small unilamellar vesicle, large
unilamellar vesicle, large multilamellar vesicle, multivesicular
vesicle, lipid layer, lipid bilayer, micelle, organelle, cell,
membrane, nucleic acid, peptide, polypeptide, protein,
oligosaccharide, polysaccharide, glycopeptide, glycolipid,
sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan,
lipid, carbohydrate, metalloprotein, proteoglycan, chromosome, cell
nucleus, acid, base, buffer, protic solvent, aprotic solvent,
nitric oxide, nitric oxide synthase, nitrous oxide, amino acid,
micelle, polymer, bone cement, copolymer, cell receptor, adhesion
molecule, cytokine, chemokine, immunoglobulin, antibody, antigen,
platelet, extracellular matrix, blood, plasma, cell ligand,
zwitterionic material, cationic material, oligonucleotide,
nanotube, or piloxymer.
[1052] In one embodiment 11540, the one or more explosive materials
include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal.
[1053] In one embodiment 11610, the at least one adhesive agent
includes one or more of an acrylic polymer or copolymer, acrylamide
polymer or copolymer polymer or copolymer, acrylamide polymer or
copolymer, polyacrylic acid, epoxy, urethane, gum arabic,
polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or
gelatin.
[1054] In one embodiment 11620, the one or more reinforcement
agents include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral matter
11630 wherein the therapeutic agent includes at least one of an
anti-tumor agent, antimicrobial agent, anti-viral agent, analgesic,
antiseptic, anesthetic, diagnostic agent, anti-inflammatory agent,
vaccine, cell growth inhibitor, cell growth promoter, immunogen,
antigen, radioactive agent, apoptosis promoting factor, enzymatic
agent, angiogenic factor, anti-angiogenic factor, hormone, vitamin,
mineral, nutraceutical, cytokine, chemokine, probiotic, coagulant,
anti-coagulant, phage, prodrug, prebiotic, blood sugar stabilizer,
smooth muscle cell activator, epinephrine, adrenaline, neurotoxin,
neuro-muscular toxin, Botulinum toxin type A, microbial cell or
component thereof, or virus or component thereof.
[1055] In one embodiment 11710, the at least one biological
remodeling agent includes one or more of a blood cell, chondrocyte,
endothelial cell, hepatocyte, keratinocyte, myocyte, osteoblast,
osteoclast, osteocyte, mesenchymal cell, stem cell, progenitor
cell, or fibroblast.
[1056] In one embodiment 11720, the at least one biological
remodeling agent includes one or more of calcium phosphate,
albumin, cytokine, pegylated cytokine, bone, cartilage, globulin,
fibrin, thrombin, glutaraldehyde-crosslinked pericardium, hide
powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin.
[1057] In one embodiment 11730, the at least one biological
remodeling agent includes one or more of Type I collagen, Type II
collagen, Type III collagen, Type VII collagen, Type X collagen,
elastin fibers, or soluble elastin.
[1058] In one embodiment 11740, the at least one biological
remodeling agent is included as part of a carrier that assists in
synthesis or activation of the at least one biological remodeling
agent.
[1059] As illustrated in FIG. 118, a cross-section of animal skin
(e.g., human skin, as shown) has multiple layers, including but not
limited to the stratum corneum (approximately 10-15 microns thick)
as part of the epidermis (approximately 100-150 microns thick). In
one embodiment, at least one frozen particle composition, at least
one frozen piercing implement, or at least one frozen piercing
implement device is administered to a substrate, such as skin, and
is configured to penetrate the stratum corneum or entire epidermis,
without reaching the underlying nerves (e.g., "sensory nerve ending
for touch," of FIG. 118). In one embodiment, at least one agent
(e.g., an anesthetic) is included in the at least one frozen
particle composition, at least one frozen piercing implement, or at
least one frozen piercing implement device that at least partially
disrupts nerve function in such a manner that even if further
frozen particle compositions, frozen piercing implements, or frozen
piercing implement devices are administered, pain is reduced or
eliminated regardless of the depth of penetration.
[1060] As illustrated in FIG. 119, in one embodiment, at least one
frozen particle composition, frozen piercing implement, or frozen
piercing implement device is administered by propelling under a
rapid expansion force (e.g., by way of at least one outlet) which
may be the result of at least one explosion. In one embodiment, the
explosion includes flash-boiling the at least one cooling liquid.
In one embodiment, the explosion includes a boiling liquid
expanding vapor explosion (BLEVE) of the at least one cooling
liquid.
[1061] The BLEVE of the cooling liquid can be calculated according
to standard techniques. For example, in FIG. 119, a diagram of the
relationship between the pressure for a substance in various phases
of liquid and gas, and the volume occupied by that substance. See,
for example, the worldwide web at: criticalprocesses.com/BLEVE.htm,
the subject matter of which is incorporated herein by reference.
The line from point A to B indicates the substance is in liquid
form and as the volume the substance occupies expands, the pressure
falls until it reaches the vapor pressure of the liquid (B) for a
particular temperature. Id. The liquid then evaporates to become a
liquid-gas mixture, and the pressure stays constant at the vapor
pressure. Eventually the substance reaches point C, where the
liquid has been converted to gas phase, and the pressure drops with
further expansion. Id.
[1062] If the pressure falls suddenly, the substance can become
unstable liquid along the line from point B to point S. Id. S is
known as a spinodal point, and the slope of the line at this point
is zero (i.e. (.alpha.p/.alpha.V)=0). Id. The dotted line connects
spinodal points at different temperatures, forming the spinodal
curve, and ending at the critical point. Id. During a BLEVE,
density variations develop spontaneously and homogenously into
liquid and gas regions. Id. The rise in pressure on the vapor
pressure line from point B to C occurs rapidly, and a BLEVE
results. Id.
[1063] As illustrated in FIG. 120, for carbon dioxide, conditions
for inducing a BLEVE can be calculated for a particular substance
since the entropy of the system remains constant. Id. Thus,
conditions that induce a BLEVE for any particular substance are
found along the spinodal curve for that substance, between 1 bar
and the critical point where the curve ends. Id.
[1064] As illustrated in FIG. 121, various embodiments of frozen
particle compositions or frozen piercing implements (alone, or as
part of a device), include different sizes, shapes, or
configurations. In one embodiment (as depicted in FIG. 121A), the
frozen particle composition or frozen piercing implement includes a
tip (or distal end), a shaft, and a base (or proximal end). As
indicated in FIG. 121A, the height, width, or breadth can vary
according to particular parameters for making or administering the
at least one frozen particle composition or frozen piercing
implement. In one embodiment, multiple different frozen particle
compositions or frozen piercing implements are included in a
device, wherein multiple different parameters (including but not
limited to size, shape, density, height, width, breadth, or
configuration) are included.
[1065] In one embodiment, FIG. 121B includes a frozen particle
composition or frozen piercing implement with at least one cavity.
As disclosed herein, in one embodiment, the at least one cavity
includes at least one solid, liquid, gas, or other form of
substance. In one embodiment, the at least one cavity includes at
least one agent. Various non-limiting examples of agents are
described herein. In one embodiment, the at least one frozen
particle composition or frozen piercing implement includes at least
one channel. In one embodiment, as indicated in FIG. 121B, the at
least one frozen particle composition or frozen piercing implement
includes multiple cavities. As illustrated in FIG. 121C, in one
embodiment, the at least one frozen particle composition or frozen
piercing implement includes at least one of a tapered, mushroom
shaped, beveled, serated, or other configuration (respectively from
left to right in the figure).
[1066] As illustrated in FIG. 122, strength of frozen piercing
implements is indicated by a sudden drop in force at the point of
failure. See, for example, Park et al., Ibid. The maximum force
just prior to the sudden drop defines the force of the piercing
implement failure. As shown in FIG. 122, according to the published
study, microneedles containing polylactic acid with a height of
approximately 800 .mu.m and a base diameter of approximately 200
.mu.m display a failure force of approximately 0.50 Newtons/needle,
which is approximately three times greater than the force needed
for insertion into skin. See, for example, Park et al, J. Contr.
Rel., vol. 104, pp. 51-66 (2005), which is incorporated herein by
reference.
[1067] As illustrated in FIG. 123, in one embodiment, at least one
frozen particle composition, frozen piercing implement, or frozen
piercing implement device includes at least one shape or
configuration illustrated. In one embodiment, the at least one
frozen particle composition, or frozen piercing implement includes
at least one cavity or channel. For example, FIG. 123A illustrates
a conical shape, FIG. 123B illustrates a cylindrical and conical
hybrid, FIG. 123C indicates another conical shape, FIG. 123D
illustrates a pyramidal shape, FIG. 123E illustrates a cuboidal and
pyramidal hybrid,
[1068] FIG. 123F illustrates a cylindrical shape, FIG. 123G
illustrates several planar rectangular shapes attached to a support
structure (e.g., for a frozen piercing implement device), and FIG.
123H illustrates several planar triangular shapes attached to a
support structure (e.g., for a frozen piercing implement
device).
[1069] As illustrated in FIG. 124, in one embodiment at least one
frozen piercing implement device 12400 includes multiple frozen
piercing implements contacting a support structure. In one
embodiment, at least one frozen piercing implement is made by
contacting at least one fluid 12420 with at least one frame 12430
defining at least one projection, raising the at least one frame
approximately vertically from the at least one fluid, such that the
surface tension of the at least one fluid is maintained, forming at
least one fluid extension 12420 (FIGS. 124D-G); exposing the at
least one fluid extension to conditions for a time sufficient to
solidify the at least one fluid'extension 12420 (FIGS. 124D-G) in
the form of at least one frozen particle composition or frozen
piercing implement. In one embodiment, the fluid 12420 is located
on at least one support structure 12410. Subsequent to making the
at least one frozen piercing implement from the fluid extension,
the implement can remain on the support structure, or be
removed.
[1070] As illustrated in FIG. 125, at least one frozen piercing
implement includes at least one functionalized surface 12560. In
one embodiment (FIG. 125 A) at least one inner surface 12550 of the
at least one frozen piercing implement 12590 is functionalized. For
example, the inner surface may include at least one carboxylic
group 12510, capable of providing a surface tending toward a
hydrophilic, or anionic surface. In one embodiment (FIG. 125 B) at
least one outer surface 12560 of the at least one frozen piercing
implement is functionalized. For example, the outer surface may
include at least one lipid group 12540, capable of providing a
surface tending toward a hydrophobic, or lipophilic surface. In one
embodiment (FIGS. 125 C and 125 D) at least one inner surface of
the at least one frozen piercing implement is functionalized. For
example, the inner surface may include at least one amino group
12585, capable of providing a surface tending toward a hydrophilic,
cationic surface. In one embodiment (FIG. 125 E) at least one
surface of the frozen piercing implement includes at least one
silane group 12595. For example, the surface may be modified to
include at least one alkoxysilane of Formula I:
(R.sup.2)Si(R.sup.1).sub.3 (Formula I), wherein R.sup.1 includes at
least one of a chlorine, acetoxy, or alkoxy, and R.sup.2 includes
at least one of an organofunctional group (e.g. methyl, phenyl,
isobutyl, octyl, --NH(CH.sub.2).sub.3NH.sub.2, epoxy, methacryl,
etc.), alkyl, aryl, amino, methacryloxy, or epoxy. In one
embodiment, the Formula I silanized surface may be capable of
imparting at least one property of nonpolar, hydrophilic,
hydrophobic, organophilic, lipophilic, lipophobic, acidic, basic,
neutral, increased or decreased permeability, or combinations
thereof. See, for example, U.S. Patent Application Publication No.
2008/0078376, which is incorporated herein by reference.
[1071] In one embodiment, the inner surface 12550 is functionalized
with a charged group 12575. In one embodiment, the underside of the
support structure 12580 is in fluid communication with at least one
compartment (not shown). In one embodiment, the topside of the
support structure 12530 can also be functionalized 12570.
[1072] In one embodiment, the at least one functionalized surface
12560 includes one or more functionalities including one or more of
charge functionality, hydrophobic functionality, hydrophilic
functionality, chemically reactive functionality, organo
functionality, or wetability. In one embodiment, the at least one
functionalized surface 12560 includes one or more functional groups
including at least one of an agent, alcohol, hydroxyl, amine,
aldehyde, dye, ketone, carbonyl, thiol, alkoxysilane, phosphate,
carboxyl, carboxylic acid, carboxylate, nucleic acid, amino acid,
polypeptide, protein, lipid, carbohydrate, metal, --NH.sub.3.sup.+,
--COOH, --COO--, --SO.sub.3, CH.sub.2N.sup.+(CH.sub.3).sub.3,
--(CH.sub.2).sub.xCH.sub.3, --C((CH.sub.2).sub.xCF.sub.3).sub.3,
--CH.sub.2N(C.sub.2H.sub.5).sub.2, --NH.sub.2,
--(CH.sub.2).sub.xCOOH, --(OCH.sub.2CH.sub.2).sub.xCH.sub.3,
--SiOH, or --OH.
[1073] In one embodiment, the at least one functionalized surface
12560 includes at least part of an outer surface. In one
embodiment, the at least one functionalized surface includes at
least part of an inner surface 12550.
[1074] As illustrated in FIG. 126, in one embodiment, at least one
frozen particle composition, frozen piercing implement, or
component of a frozen piercing implement device 12600 includes at
least one distal end, or tip, 12810, and a proximal end, or base
end, 12820. In one embodiment, the frozen particle composition or
frozen piercing implement includes at least one channel 12800. In
one embodiment, the at least one channel includes at least one
inner surface 12830 and at least one outer surface 12860. In one
embodiment, the frozen particle composition or frozen piercing
implement are substantially solid in form. As indicated by FIGS.
126A through 126G, the frozen particle compositions or frozen
piercing implements can take a variety of forms, shapes, or
configurations. For example, FIGS. 126C-126D illustrate at least
one frozen piercing implement including at least one beveled end.
In another example, FIG. 126G illustrates at least one frozen
piercing implement including at least one jagged end. In another
example, FIG. 126D includes at least one frozen piercing implement
including at least one blunt or substantially flattened end. In
another example, FIGS. 126A, 126B, and 126F illustrate at least one
frozen piercing implement including at least one tapered end.
[1075] As illustrated in FIG. 127 A, in one embodiment, an array
device comprises a body portion 12720, including a support
structure having a surface 12725; and a plurality of piercing
implements 12750 extending substantially outward from the support
structure 12725. In one embodiment, the plurality of piercing
implements 12750 includes at least one frozen piercing implement
12755. In one embodiment, the device includes at least one
compartment 12700 configured to hold at least one agent to be
administered to the at least one substrate, or at least one
material extracted from the at least one substrate. In one
embodiment, at least one piercing implement 12755 is in fluid
communication with the at least one compartment 12700, and includes
a distal end opening (e.g., a port) 12740 from which at least one
agent can be administered to the at least one substrate, or at
least one material can be extracted from the at least one
substrate. In one embodiment, the device includes at least one
backing member 12710, which can be a portion of the overall support
structure 12725, and can function as an outer portion of the
support structure (e.g., in at least one embodiment, the
compartment is disposable and the backing member and/or remaining
support structure is recyclable or reusable). In one embodiment,
the backing member is an outer shell. In one embodiment, the
backing member is multi-layered (e.g., polymeric or paper-based
materials). In one embodiment, a fastening mechanism (e.g.,
adhesive, VELCRO.RTM., etc.) 12730 is included to attach the device
to the at least one substrate (e.g., the surface of a subject or
device, etc.). In one embodiment, the fastening mechanism 12730 is
at least temporarily covered by a device cover 12760.
[1076] In one embodiment, the plurality of sterile frozen piercing
implements 12750 have at least one major dimension of approximately
one centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer,
or any value therebetween.
[1077] In one embodiment, the plurality of sterile frozen piercing
implements 12750 extends substantially perpendicular to the support
structure. In one embodiment, the plurality of sterile frozen
piercing implements 12750 extends through the surface of the
support structure 12725. In one embodiment, the plurality of
sterile frozen piercing implements 12750 extends from the surface
of the support structure 12725. In one embodiment, the support
structure 12725 includes at least one frozen composition. In one
embodiment, the support structure 12725 includes at least one
frozen composition also included in at least one frozen piercing
implement 12755. In one embodiment, the support structure 12725 is
at least partially frozen. In one embodiment, the support structure
12725 and at least one frozen piercing implement 12755 of the
plurality of frozen piercing implements 12750 include at least one
common constituent. In one embodiment, the plurality of frozen
piercing implements 12750 are positioned substantially parallel to
each other.
[1078] In one embodiment, the plurality of frozen piercing
implements 12750 are positioned substantially in a predetermined
spatial pattern. In one embodiment, the predetermined spatial
pattern is at least partially periodic. See FIG. 131 for various
non-limiting examples of spatial patterns for array devices,
including at least partially periodic patterns.
[1079] In one embodiment, the plurality of frozen piercing
implements 12750 includes an area density of implements greater
than or approximately equal to 1 .mu.m, greater than or
approximately equal to 10 .mu.m, greater than or approximately
equal to 50 .mu.m, greater than or approximately equal to 100
.mu.m, greater than or approximately equal to 500 .mu.m, greater
than or approximately equal to 1 mm, greater than or approximately
equal to 10 mm, greater than or approximately equal to 50 mm,
greater than or approximately equal to 100 mm, greater than or
approximately equal to 500 mm, greater than or approximately equal
to 1 cm, or any value there between. In one embodiment, the
plurality of frozen piercing implements 12750 includes
approximately the same length.
[1080] In one embodiment, the length of a frozen piercing implement
is associated with the position or location of the frozen piercing
implement in the array device. For some non-limiting examples,
longer or taller implements may be in the center, while shorter
implements are around the periphery; longer or taller implements
may be in a particular pattern within the spatial pattern of the
array device, while shorter implements are in a different
particular pattern; implements in the center may include different
agents that extend their length (e.g. reinforcement agents); or
implements along one particular side may be longer than implements
along another particular side. In one embodiment, the length of a
frozen piercing implement is actuatable, or controllable.
[1081] In one embodiment, the at least one frozen piercing
implement is configured to be deactivated. In one embodiment, the
at least one frozen piercing implement is configured to be
deactivated by at least one component of the array device or the
frozen piercing implement. In one embodiment, the at least one
frozen piercing implement configured to be deactivated by thermal
transfer to the at least one frozen piercing implement.
[1082] In one embodiment, the plurality of frozen piercing
implements 12750 is positioned as at least a portion of a fluidic
or injection device. See FIGS. 127B, 129, and 130, for various
non-limiting examples of devices.
[1083] As illustrated in FIG. 127, in one embodiment, the plurality
of frozen piercing implements 12750 is positioned in fluid
communication with at least one compartment 12700 configured to be
mechanically regulated. In one embodiment, the plurality of frozen
piercing implements 12750 is positioned on at least one surface
12725.
[1084] In one embodiment, a fluidic device comprises a support
structure 12725 at least partially defining at least one
compartment 12700, and at least one frozen piercing implement 12755
in fluid communication with the at least one compartment 12700.
[1085] In one embodiment, at least one frozen piercing implement of
the plurality of frozen piercing implements includes one or more of
hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1086] In one embodiment, at least one frozen piercing implement
12755 of the plurality of frozen piercing implements 12750 is
configured to deliver at least one agent, and further comprises at
least one agent. In one embodiment, the at least one major
dimension includes at least one of the radius, diameter, length,
width, height, or perimeter.
[1087] In one embodiment, each frozen piercing implement 12755 of
the plurality 12750 includes at least one agent different than the
agent of every other frozen piercing implement of the plurality
12750. In one embodiment, at least one frozen piercing implement
12755 of the plurality 12750 includes at least two different
agents. In one embodiment, the device includes at least two
different agents. In one embodiment, the at least one agent
includes at least one antigen. In one embodiment, each frozen
piercing implement 12755 of the plurality 12750 includes at least
one antigen. In one embodiment, the at least one antigen includes
at least one allergen. In one embodiment, the frozen piercing
implement 12755 is configured for delivering the at least one
agent. Various non-limiting examples of agents are described
herein. In one embodiment, the at least one agent includes at least
one of a nontoxic, biocompatible, bioresorbable, or biodegradable
agent. In one embodiment, at least two frozen piercing implements
of the plurality of frozen piercing implements have at least one
agent in common. In one embodiment, each frozen piercing implement
12755 of the plurality of frozen piercing implements 12750 has at
least one agent in common. In one embodiment, each frozen piercing
implement 12755 of the plurality of frozen piercing implements
12750 is different from every other piercing implement by varying
one or more of: size of implement, shape of implement, or
constitution of implement.
[1088] In one embodiment, at least two frozen piercing implements
of the plurality 12750 of frozen piercing implement differ in one
or more of: size of implement, shape of implement, or constitution
of implement. In one embodiment, at least one frozen piercing
implement of the plurality of frozen piercing implements 12750
includes hydrogen oxide in one or more phases including at least
one of amorphous solid water, low density amorphous ice, high
density amorphous ice, very high density amorphous ice, clathrate
ice, hyperquenched glassy water, ice Ic, ice II, ice III, ice IV,
ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, ice XII,
ice XIII, ice XIV, or ice XV. In one embodiment, at least one of
the plurality of frozen piercing implements is substantially solid
at approximately 0.degree. C., approximately -10.degree. C.,
approximately -20.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -75.degree. C., approximately -80.degree. C.,
approximately -85.degree. C., approximately -90.degree. C.,
approximately -95.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -180.degree. C., approximately -200.degree. C.,
approximately -220.degree. C., approximately -250.degree. C., or
any value less than or therebetween. In one embodiment, the array
device has at least one major dimension of approximately one
centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer,
or any value therebetween.
[1089] In one embodiment, the plurality of frozen piercing
implements 12750 includes a two dimensional array, or a three
dimensional array. In one embodiment, the plurality of frozen
piercing implements are arranged in at least one configuration
including a regular or irregular shape. See for example, FIG. 130
for various non-limiting examples of array device shapes. In one
embodiment, the plurality of frozen piercing implements are
arranged in at least one configuration including at least one of a
rectangle, square, circle, triangle, or polygon. See for example,
FIG. 130.
[1090] In one embodiment, at least one frozen piercing implement of
the plurality 12750 of frozen piercing implements includes at least
one functionalized surface. See, for example, FIG. 125, for various
non-limiting examples of functionalized surfaces.
[1091] In one embodiment, the array device includes at least one
attachment component 12730 configured to secure the array device to
at least one substrate. In one embodiment, the at least one
attachment component 12730 includes at least one adhesive material.
In one embodiment, the device is configured to substantially form a
patch. In one embodiment, the array device further comprising at
least one compartment 12700. In one embodiment, the at least one
compartment includes, for example, at least one syringe or valve.
See, for example, FIG. 130 for various non-limiting examples of a
syringe and valve. In one embodiment, the at least one compartment
12700 is configured to hold at least one material extracted from at
least one substrate. In one embodiment, the at least one
compartment 12700 is in fluid communication with at least one
frozen piercing implement of the plurality of frozen piercing
implements. In one embodiment, the at least one compartment 12700
is configured for holding at least one agent. In one embodiment,
the at least one compartment 12700 is configured for holding at
least one cryogenic substance.
[1092] In one embodiment, the frozen piercing implement is
configured to pierce at least one substrate to a depth of
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 .mu.m, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, or any value therebetween.
In one embodiment, the at least one frozen piercing implement is
configured to abrade or ablate at least one substrate surface
12895. In one embodiment, the plurality of frozen piercing
implements 12750 is positioned such that each frozen piercing
implement of the array device contacts a single cell of at least
one biological tissue. In one embodiment, at least one implement of
the plurality of frozen piercing implements includes at least one
sensor.
[1093] In one embodiment, at least one implement of the plurality
of frozen piercing implements 127500 is configured for extracting
at least one material from at least one substrate 12895. Specific
non-limiting examples of materials that are capable of being sensed
or extracted from at least one substrate are provided herein.
[1094] In one embodiment, at least one implement of the plurality
of frozen piercing implements further includes at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, glycopeptide, glycolipid, lipoprotein, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus,
acid, support structure, buffer, protic solvent, aprotic solvent,
nitric oxide, nitrous oxide, nitric oxide synthase, amino acid,
micelle, polymer, copolymer, monomer, prepolymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
nanotube, piloxymer, transfersome, gas, element, contaminant,
radioactive particle, hormone, microorganism, bacteria, virus,
quantum dot, contrast agent, or any part thereof.
[1095] In one embodiment, the plurality of frozen piercing
implements 12750 includes at least approximately 2 implements,
approximately 5 implements, approximately 10 implements,
approximately 20 implements, approximately 50 implements,
approximately 100 implements, approximately 200 implements,
approximately 300 implements, approximately 400 implements,
approximately 500 implements, approximately 600 implements,
approximately 700 implements, approximately 800 implements,
approximately 900 implements, approximately 1000 implements,
approximately 5000 implements, approximately 10000 implements, or
any value therebetween or greater.
[1096] In one embodiment, the spacing between two or more frozen
piercing implements includes at least approximately 1 nm,
approximately 5 nm, approximately 10 nm, approximately 20 nm,
approximately 50 nm, approximately 80 nm, approximately 100 nm,
approximately 200 nm, approximately 300 nm, approximately 400 nm,
approximately 500 nm, approximately 600 nm, approximately 700 nm,
approximately 800 nm, approximately 900 nm, approximately 1 .mu.m,
approximately 5 .mu.m, approximately 10 .mu.m, approximately 15
.mu.m, approximately 20 .mu.m, approximately 50 .mu.m,
approximately 100 .mu.m, approximately 120 .mu.m, approximately 150
.mu.m, approximately 200 .mu.m, approximately 500 .mu.m,
approximately 1 mm, approximately 5 mm, approximately 10 mm,
approximately 100 mm, approximately 500 mm, approximately 1 cm,
approximately 5 cm, approximately 10 cm, or any value therebetween
or greater.
[1097] As illustrated in FIG. 127 B, in on embodiment, the frozen
piercing implement includes at least one distal end 12775, at least
one frozen piercing implement shaft 12735, which may include at
least one channel 12755, or port (e.g., outlet or inlet ports at
the distal end 12765 or proximal end 12705). In one embodiment, the
device includes at least one sensor, valve, gate, transducer,
actuator, detector, heater, circuit, on-chip electronics, or other
features 12745 are located in the body of the device 12725. In one
embodiment, at least one electrode contact site 12715 serves as an
outside connection to at least one resistor 12785, which may be
utilized to form a thermally driven, cascaded bubble pump or
heater. In one embodiment, the device includes at least one
compartment 12705 configured to hold at least one agent or at least
one material extracted from at least one substrate. Such devices
may include a micro- or nano-scale, as well as larger scales.
[1098] In one embodiment, the at least one frozen piercing
implement includes at least one port (e.g., 12765, 12705). The at
least one port can be an inlet port, or an outlet port, and may
vary according to the relative use of the device. For example, in
one embodiment, a first port 12705 functions as an inlet port when
administering at least one agent to at least one substrate by way
of a second port 12765 functioning as an outlet port. In another
example, in one embodiment a first port 12765 functions as an inlet
port when extracting at least one material from at least one
substrate. In one embodiment, the at least one material is analyzed
or manipulated while still in the device (according to at least one
feature 12745), or the at least one material exits the device by
way of at least one port 12705 functioning as an outlet port. In
one embodiment, at least one outlet port is in fluid communication
with at least one inlet port.
[1099] As illustrated in FIG. 128, in one embodiment, the plurality
of implements is included in an array positioned on a support
structure 12865 that has a surface 12880. In one embodiment, the at
least one frozen piercing implement 12840 includes at least one
channel 12850 that includes at least one inner surface 12830 and at
least one outer surface 12860. In one embodiment, the frozen
piercing implement includes a distal end 12810 and a proximal end
12820. In one embodiment, the frozen piercing implement 12840
includes a channel 12850 that includes at least one opening 12800.
In one embodiment, the at least one channel 12850 is in fluid
communication with at least one fluidics device (FIGS.
128C-128D).
[1100] In one embodiment, the array device includes at least one
channel 12890. In one embodiment, the at least one channel 12890
includes at least one cross-coupling flow channel 12890. In one
embodiment, the array device includes at least one compartment
12870. In one embodiment, the at least one compartment 12870 is in
fluid communication with the at least one channel 12890. In one
embodiment, the array device includes at least one agent. In one
embodiment, the agent is included in the at least one compartment
12870. In one embodiment, the at least one compartment is
configured to hold at least one agent, or at least one material
extracted from at least one substrate 12895.
[1101] In one embodiment, at least one frozen piercing implement of
the plurality of frozen piercing implements includes at least one
inlet port 12800A or 12800B. In one embodiment, the at least one
inlet port 12800A or 12800B is in fluid communication with at least
one channel 12890 of at least one frozen piercing implement. In one
embodiment, the at least one inlet port 12800A or 12800B is in
fluid communication with at least one channel 12890 of the array
device. In one embodiment, at least one frozen piercing implement
of the plurality of frozen piercing implements includes a plurality
of inlet ports. In one embodiment, at least one frozen piercing
implement of the plurality of frozen piercing implements includes
at least one outlet port 12800B or 12800A. In one embodiment, the
at least one outlet port 12800B or 12800A is in fluid communication
with at least one channel 12890 of at least one frozen piercing
implement. In one embodiment, the at least one outlet port 12800B
or 12800A is in fluid communication with at least one channel 12890
of the array device. In one embodiment, at least one frozen
piercing implement of the plurality of frozen piercing implements
includes a plurality of outlet ports 12800B or 12800A.
[1102] In one embodiment, the array device further comprises at
least one of a nanoparticle, microparticle, sensor, valve, gate,
channel, transducer, actuator, detector, heater, circuit, or
detection material. The location of these features may vary
according to the device (e.g., the distal end 12810, the proximal
end 12820, any location along the shaft or channel of the implement
12800, 12830). See, for particular non-limiting examples, FIGS.
128, and 129.
[1103] As illustrated in FIG. 129, in one embodiment, the frozen
piercing implement device includes at least one actuator structure
12910, optionally integral with the at least one support structure
12925 of the frozen piercing implement(s). In one embodiment, a
fluidic device comprises at least one frozen piercing implement,
and at least one actuator 12910 configured to actuate the at least
one frozen piercing implement 12800.
[1104] In one embodiment, the at least one actuator 12910 includes
at least one of a piezoelectric actuator, electrostatic actuator,
thermal actuator, shape-memory alloy actuator, bioactuator, or
magnetic actuator. In one embodiment, the actuator includes a
microactuator or a nanoactuator. In one embodiment, at least one
feature 12940 or 12930 (e.g., channel, pump, sensor, injector,
actuator, heater, detector, controller, transducer, receiver,
cooler, transmitter, circuit, lens, tunablelens, valve, gate,
nanoparticle, microparticle, power source, or detection material,
etc.) is located in the body 12900 of the device. In one
embodiment, the valve includes at least one of a one-way valve, or
pressure settable valve.
[1105] In one embodiment, the at least compartment 12920 is
configured to hold at least one material extracted from at least
one substrate 12970. In one embodiment, the fluidic device includes
at least one means for drawing up the at least one material from
the at least one substrate 12970. In one embodiment, at least one
piercing implement 12800 is in fluid communication with at least
one compartment 12920. In one embodiment, the sensor is configured
to respond to at least one material collected in the at least one
compartment 12920. In one embodiment, the at least one compartment
12920 is configured for displacement of at least one fluid as the
at least one material is extracted from the at least one substrate
12970. In at least one embodiment, the at least one compartment
12920 is substantially rigid. See, FIG. 130 for other non-limiting
examples of compartments. In one embodiment, the at least one
compartment 12920 is substantially deformable. See FIGS. 133-134
for other non-limiting examples of compartments. In one embodiment,
the fluidic device includes at least one cantilever 12955. In one
embodiment, the at least one cantilever 12955 is integral with the
at least one actuator 12910. In one embodiment, the at least one
cantilever 12955 is supported by the body 12900, or other
structures within the body 12900 of the device.
[1106] As described herein for other embodiments of frozen piercing
implements or frozen piercing implement devices, in one embodiment,
the at least one frozen piercing implement or device includes at
least one agent. Various non-limiting examples of agents are
provided herein. In particular, in one embodiment, the agent
includes at least one of an antimicrobial, citrate, EDTA,
anticoagulant, or other agent.
[1107] As described herein for other embodiments of frozen piercing
implements or frozen piercing implement devices, in one embodiment,
the at least one frozen piercing implement is configured to
transform to another phase state upon the occurrence of at least
one inducible event. In one embodiment, the at least one inducible
event includes one or more of: administration of the device to at
least one substrate, contacting the at least one frozen piercing
implement with at least one substrate, increasing the temperature
of the at least one frozen piercing implement, increasing the
temperature of the at least one substrate, increasing the pressure
on the at least one frozen piercing implement, increasing the
pressure on the at least one substrate, altering a magnetic field
on the at least one frozen piercing implement, altering a magnetic
field on the at least one substrate, administering at least one
additional agent to the at least one frozen piercing implement,
administering at least one additional agent to the substrate,
administering at least one electric field to the at least one
frozen piercing implement, administering at least one electric
field to the at least one substrate, administering ultrasound to
the at least one frozen piercing implement, administering
ultrasound to the at least one substrate.
[1108] As illustrated in FIG. 129, in one embodiment, the fluidic
device including at least one frozen piercing implement 12800,
includes at least one actuator 12910. In one embodiment, at least
one controller 12960 is configured to control the at least one
actuator 12910. The controller 12960 may include, for example, a
mechanical or electrical controller. In one embodiment, the
controller 12960 includes a wireless controller. In one embodiment,
the device includes at least one sensor 12950 configured to sense
at least one material extracted from the at least one substrate
12970 (e.g., the material passes through the at least one piercing
implement 12800 or is extracted by force from the at least one
piercing implement changing phase and retreating). In one
embodiment, the at least one frozen piercing implement 12800 is
integral with the at least one actuator 12910. In one embodiment,
the at least one sensor is configured to detect at least one
material from the at least one substrate 12970. Several
non-limiting examples of materials capable of being sensed are
disclosed herein.
[1109] In various embodiments disclosed herein, the support
structure (e.g., 12880, 12925, 13030, etc.) includes at least one
frozen composition. In one embodiment, the support structure
(12900) includes at least one of a metal, ceramic, polymer, organic
or inorganic compound, semiconductor, other material, or composite
thereof.
[1110] In one embodiment, the at least one compartment 12920
expands as at least one material is extracted. See FIG. 134 for
other non-limiting examples of compartments. In one embodiment, the
at least one compartment 12920 is substantially fabricated from one
or more of a polymer, metal, ceramic, semiconductor, frozen
composition, other material, or composite thereof.
[1111] In one embodiment, the at least one actuator 12910 includes
at least one of a piezoelectric actuator, electrostatic actuator,
thermal actuator, shape-memory alloy actuator, bioactuator, or
magnetic actuator. In one embodiment, the at least one frozen
piercing implement is integral with one or more of the at least one
of a channel, pump, sensor, injector, actuator, heater, detector,
controller, transducer, receiver, transmitter, circuit, lens,
cooler, tunablelens, valve, gate, channel, nanoparticle,
microparticle, power source, or detection material. See, for
example, FIGS. 127-131 for various non-limiting examples of
particular embodiments.
[1112] As illustrated in FIG. 130, in one embodiment, a frozen
piercing implement device includes at least one injection or
fluidic device 13000. In one embodiment, the injection device 13000
includes at least one auto-injection device. In one embodiment, a
plurality of piercing implements 13040, including at least one
frozen piercing implement, is employed in the injection device. In
one embodiment, a single frozen piercing implement is employed (not
shown). In one embodiment, the plurality of piercing implements
13040 are positioned on at least one support structure 13030. In
one embodiment, the piercing implement(s) 13040 are in fluid
communication with at least one compartment 13010 configured to
hold at least one agent for administration to at least one
substrate, or at least one material extracted from at least one
substrate. In one embodiment, the piercing implement(s) 13040 can
be contracted (FIG. 130A) or extended (FIG. 130B). In one
embodiment, a mechanical controller (e.g., plunger) 13020 is
configured to control at least one of the position of the piercing
implement(s) 13040, or the level of contents of the at least one
compartment 13010.
[1113] In one embodiment, at least one first implement of the
plurality of implements 13040 is configured to deliver at least one
agent, and at least one second implement of the plurliaty of
implements 13040 is configured to sense or extract at least one
material from the at least one substrate 13050. In one embodiment,
the at least one first implement is configured to deliver an agent
that is different than the at least one second implement.
[1114] In one embodiment, the fluidic device includes at least one
of a channel, pump, sensor, injector, actuatory, heater, detector,
controller, transducer, receiver, cooler, transmitter, circuit,
lens, tunablelens, valve, gate, nanoparticle, microparticle, power
source, or detection material (e.g., in the compartment, in the
support structure, in at least one frozen piercing implement,
etc.). The location of these various features can vary, depending
on the particular embodiment. For example, such features may be
found in the at least one compartment 13010, in or near the
mechanical controller 13020, near the proximal or distal end of the
at least one compartment 13010, in or near the at least one support
structure 13030, or in or near the at least one frozen piercing
implement 13040. See FIG. 129 for other non-limiting examples of
particular embodiments.
[1115] As illustrated in FIG. 131, a frozen piercing implement
device including a plurality of piercing implements, including at
least one frozen piercing implement 12600, includes at least one
topside of a support structure 13180, and at least one underside of
the at least one support structure 13190. In one embodiment, the
frozen piercing implement device can be fabricated into various
shapes (13100, 13120, 13140, 13160) or configurations (13110,
13130, 13150, 13170).
[1116] As illustrated in FIG. 132, a frozen piercing implement
device 13205 is included in at least one system 13200 for
administration to at least one substrate 13250, or extraction of at
least one material from at least one substrate 13250. In one
embodiment, the device includes at least two electrode assemblies
(13210, 13212) and an integrated power source 13220. In one
embodiment, the device includes at least one frozen piercing
implement 13230, and at least one support structure 13240.
[1117] As illustrated in FIGS. 133-134, in one embodiment, the
array device includes a plurality of compartments 13370 in fluid
communication with at least one frozen piercing implement 13360 of
the plurality of frozen piercing implements 13380. In one
embodiment, the plurality of compartments 13370 includes at least
one first compartment (e.g., 13370A) configured to hold at least
one different substance from at least one second compartment (e.g.,
13370B or 13370C).
[1118] In one embodiment, the plurality of compartments 13370
includes at least one first compartment (e.g., 13370A) configured
to hold at least one first agent, wherein the at least one first
agent is different from at least one other agent located in at
least one second compartment (e.g., 13370B or 13370C). In one
embodiment, the plurality of compartments 13370 includes at least
one first compartment configured to hold at least one first agent,
and at least one second compartment configured to hold a
pharmaceutically acceptable carrier or excipient.
[1119] In one embodiment, two or more compartments (e.g., 13370A,
13370B, or 13370C) are configured to interact with at least one
means for intermixing the contents of the two or more compartments
prior to or during administration of the array device to at least
one substrate. In one embodiment, the at least one means for
intermixing includes mechanical disruption of at least one
compartment, altering porosity of at least one compartment,
electrochemical degradation of at least one compartment, valve
opening of at least one compartment, chemical degradation of at
least one compartment, or altering magnetic field of at least one
compartment. In one embodiment, the contents of the two or more
compartments are intermixed during administration by way of contact
of the one or more piercing implements 13380 with the at least one
substrate.
[1120] In one embodiment, the array device is in electronic
communication with at least one computing device.
[1121] In one embodiment, a composition comprises a plurality of
piercing implement array devices joined together, the piercing
implement array devices including at least one frozen piercing
implement. See, for example, FIGS. 131-132 for various non-limiting
examples of arrays that can be joined together in particular
embodiments.
[1122] As illustrated in FIG. 133, in one embodiment, the frozen
piercing implement device 13300, includes at least one frozen
piercing implement 13360. In one embodiment, the at least one
frozen piercing implement 13360 includes at least one channel
13310. In one embodiment, the at least one channel 13310 is in
fluid communication with at least one compartment 13320, or
plurality of compartments 13370. In one embodiment, the at least
one compartment is configured to hold at least one agent to be
administered to the at least one substrate, or at least one
material extracted from the at least one substrate. In one
embodiment, the plurality of compartments can include multiple
compartments for administration or extraction. In one embodiment,
the same compartment can be utilized for both administration of at
least one agent, and for collection of extracted material from the
at least one substrate. In one embodiment, the at least one frozen
piercing implement 13360 is positioned on at least one support
structure 13330. In one embodiment, the at least one support
structure includes at least one frozen fluid or frozen composition.
In one embodiment, the at least one compartment 13320 is configured
to at least partially deflate (thereby expelling any contents) or
at least partially inflate (thereby extracting or collecting at
least one material from at least one substrate) by way of a
separate component 13340, including an expandable component. In one
embodiment, the frozen piercing implement device includes at least
one backing member, such as a rim or shell 13350 of the support
structure configured to secure the at least one component 13340 or
at least one compartment 13320. In one embodiment, the at least one
compartment 13320 is configured to at least partially deflate or
inflate by way of direct pressure on the compartment.
[1123] In one embodiment, a composition comprises a support means
for an array device, wherein the array device includes one or more
frozen piercing implements. See, for example, FIGS. 132-134 for
various non-limiting examples of support means for various array
device embodiments (e.g., 13330). In one embodiment, the support
means 13330 is seperable from the one or more frozen piercing
implements. In one embodiment, at least part of the support means
13330 is at least partially frozen. In one embodiment, the at least
partially frozen support means 13330 and the one or more frozen
piercing implements include at least one frozen constituent in
common. In one embodiment, the one or more frozen piercing
implements have at least one major dimension of approximately one
centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer,
or any value therebetween.
[1124] In one embodiment, a method of administering at least one
array device to at least one substrate comprises contacting at
least one array device to at least one substrate, wherein the array
device includes at least one frozen piercing implement.
[1125] In one embodiment, a method of vaccinating a subject
comprises administering to a subject at least one frozen piercing
implement array device; wherein the at least one frozen piercing
implement array device includes at least one frozen piercing
implement including at least one vaccine.
[1126] As illustrated in FIG. 140, in one embodiment, the frozen
piercing implement device (FIGS. 140A-C), includes at least one
frozen piercing implement 14090. In one embodiment, the device
includes at least one valve 14070. In one embodiment, the valve
maintains a sealed compartment 14060. In one embodiment, the valve
maintains air pressure equilibrium between the at least one
compartment 14060 and the surrounding area during actuation of the
bridge 14000.
[1127] In one embodiment, the device includes at least one
compartment 14060 configured to hold at least one agent to be
administered to at least one substrate 14080, or configured to hold
at least one material extracted or collected from at least one
substrate 14080. In one embodiment, the device includes at least
one actuator bridge 14000 supported by at least one support
structure 14010. In one embodiment, the device includes at least
one sensor 14020 located in the at least one compartment 14060, or
sidewall 14030. In one embodiment, the device includes at least one
fastening or adhesive mechanism 14040 for adhering the device to
the at least one substrate 14080. In one embodiment, the actuator
bridge 14000 is configured to cause the at least one frozen
piercing implement 14090 to contact the at least one substrate
14080 when at least one vertical force 14050 is placed on the
bridge of the actuator 14000.
[1128] In one embodiment, the actuator is driven by at least one of
mechanical, magnetic, electric, or electromagnetic force. See, for
example, Zhao, et al., Abstract, Information Acquisition, 2005 IEEE
Int'l Conf, Jun. 27-Jul. 3, 2005, which is incorporated herein by
reference.
[1129] In on embodiment, the amount of force needed to pierce the
at least one substrate is approximately 1 mN, approximately 10 mN,
approximately 20 mN, approximately 30 mN, approximately 40 mN,
approximately 50 mN, approximately 60 mN, approximately 70 mN,
approximately 80 mN, approximately 90 mN, approximately 100 mN,
approximately 150 mN, approximately 200 mN, approximately 250 mN,
approximately 300 mN, approximately 350 mN, approximately 400 mN,
approximately 450 mN, approximately 500 mN, approximately 550 mN,
approximately 600 mN, approximately 650 mN, approximately 700 mN,
approximately 750 mN, approxiatmely 800 mN, approximately 850 mN,
approximately 900 mN, approximately 1 N, approximately 2 N,
approximately 3 N, approximately 4 N, approximately 5 N, or any
value less than or therebetween. In one embodiment, the amount of
force needed to pierce the at least one substrate includes at least
one predetermined value. In one embodiment, the amount of force
needed to pierce the at least one substrate is calculated based on
at least one characteristic or property of the substrate. In one
embodiment, the amount of force needed to pierce the at least one
substrate depends on at least one characteristic or property of the
frozen piercing implement, or frozen piercing implement device.
Examples of such properties are disclosed herein.
[1130] For example, the vertical force F, which is required to
penetrate the substrate, can be calculated by multiplying the
lateral force F.sub.1 on the bridge upon deflection, with the sine
of the deflection angle a relative to resting. In one embodiment,
by increasing the horizontal width w increases the actuation force
at the tip of the cantilever bridge. Likewise, in one embodiment,
an electrical voltage can be applied to actuate the
cantilever-tip.
[1131] In one embodiment, the frozen piercing implement device
includes at least one sensor. In one non-limiting example, the
sensor includes an electrochemical transducer in which current is
converted from chemical to electrical energy through oxidation or
reduction at the electrode surface. See, for example, U.S. Patent
Application Publication No. 20050228313, which is incorporated
herein by reference. In one embodiment, the at least one sensor
includes at least one sensor to monitor at least one material in
the at least one substrate (e.g., glucose, insulin, etc.). Some
non-limiting examples of materials that can be detected or analyzed
are disclosed herein.
[1132] In one embodiment, the transducer includes a small metal
electrode that is insulated except at a particular location where
the chemical reaction occurs. At the reaction location, several
electrochemical analytical and synthetic systems are implemented.
The type of electrode sensor utilized with the device can be varied
according to the electrical parameter being measured. For example,
in the case of glucose measurement, potentiometric and emperometric
sensors can be utilized. Id. The output signal from the at least
one sensor can be displayed, for example, on an active or passive
display. In one embodiment, the frozen piercing implement device
includes at least one power source for operation of, for example,
the actuator, sensor, corresponding transceiver or electronics. As
described herein, in one embodiment, the power source includes, for
example, a battery, fuel cell, capacitor, or DC power supply.
[1133] As illustrated in FIGS. 135-139, a computer-implemented
method 13500, comprises: 13510 receiving one or more signals that
include information related to accepting input associated with at
least one parameter for making or administering at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate; 13520 wherein the at
least one frozen particle composition or frozen piercing implement
includes at least one agent; 13530 receiving one or more signals
that include information related to evaluating the at least one
substrate for one or more indicators of administration of the at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device; 13540 processing the
information related to the input associated with at least one
parameter for making or administering the at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate and the information
related to the evaluating the at least one substrate; and 13550
generating an output to a user readable display. In one embodiment
13560, evaluating at least one substrate for one or more indicators
includes evaluating at least one of an assay, image, or gross
assessment of the at least one substrate prior to, during, or
subsequent to at least one administration of at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 13570, the assay includes at
least one technique that includes spectroscopy, microscopy,
electrochemical detection, polynucleotide detection, histological
examination, biopsy analysis, fluorescence resonance energy
transfer, electron transfer, enzyme assay, electrical conductivity,
isoelectric focusing, chromatography, immunoprecipitation,
immunoseparation, aptamer binding, filtration, electrophoresis,
immunoassay, or radioactive assay.
[1134] In one embodiment 13610, the image includes at least one
image acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment 13620 receiving one or more
signals includes receiving one or more signals associated with
selection of at least one parameter for making or administering the
at least one frozen particle composition, frozen piercing
implement, or frozen piercing implement device.
[1135] In one embodiment 13630, wherein the at least one parameter
for making the at least one frozen piercing implement device
includes one or more of: constitution of the at least one frozen
piercing implement of the frozen piercing implement device,
constitution of the at least one frozen piercing implement device,
formulation of the at least one frozen piercing implement of the
frozen piercing implement device, formulation of the at least one
frozen piercing implement device, size of the at least one frozen
piercing implement of the frozen piercing implement device, size of
the at least one frozen piercing implement device, shape of the at
least one frozen piercing implement of the frozen piercing
implement device, shape of the at least one frozen piercing
implement device, physical structure of the at least one frozen
piercing implement of the frozen piercing implement device,
physical structure of the at least one frozen piercing implement
device, physical or chemical integrity of the at least one frozen
piercing implement of the frozen piercing implement device,
physical or chemical integrity of the at least one frozen piercing
implement device, or presence or absence of at least one
microparticle, nanoparticle, lens, tunable lens, sensor,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, energy source, injector, controller,
receiver, transmitter, or circuit, in the at least one frozen
piercing implement or frozen piercing implement device.
[1136] In one embodiment 13710, at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
[1137] In one embodiment 13720, the input associated with at least
one parameter for making the at least one frozen particle
composition or frozen piercing implement includes one or more
property including: constitution of the at least one frozen
particle composition or frozen piercing implement, configuration of
the at least one frozen particle composition or frozen piercing
implement, formulation of the at least one frozen particle
composition or frozen piercing implement, size of the at least one
frozen particle composition or frozen piercing implement, density
of the at least one frozen particle composition or frozen piercing
implement, shape of the at least one frozen particle composition or
frozen piercing implement, physical structure of the at least one
frozen particle composition or frozen piercing implement, physical
or chemical integrity of the at least one frozen particle
composition or frozen piercing implement.
[1138] In one embodiment 13730, the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent.
[1139] In one embodiment 13810, the input associated with at least
one parameter for administering at least one frozen particle
composition or frozen piercing implement to at least one substrate
includes one or more of: substrate type; substrate function;
substrate size; substrate constitution; substrate architecture;
substrate durability; substrate temperature; temperature of
administration conditions; depth of administration of the at least
one frozen particle composition or frozen piercing implement;
substrate source; one or more temporal coordinates; one or more
spatial coordinates; presence or absence of at least one agent;
presence or absence of at least one microparticle, nanoparticle,
lens, tunablelens, sensor, transducer, actuator, detector, heater,
valve, gate, channel, detection material, pump, power source,
injector, controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen particle composition or
frozen piercing implement; force of administration of the at least
one frozen particle composition or frozen piercing implement;
velocity of administration of the at least one frozen particle
composition or frozen piercing implement; quantity of frozen
particle compositions or frozen piercing implements administered;
rate of administration of more than one frozen particle
compositions or frozen piercing implements; method of
administration of at least one frozen particle composition or
frozen piercing implement; timing of administration of at least one
frozen particle composition or frozen piercing implement; or rate
of delivery of at least one agent.
[1140] In one embodiment 13820, the at least one substrate includes
one or more of a cell, tissue, organ, structure, device, or food
product. In one embodiment 13830, the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device includes one or more of hydrogen oxide, nitrogen,
oxygen, air, helium, neon, argon, xenon, chlorine, bromine, carbon
dioxide, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl
formamide, dioxane, tetrahydrofuran, acetonitrile, acetic acid,
n-butanol, isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1141] In one embodiment 13910, the output includes one or more
instructions for making the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 13920, the output includes at
least one graphical description of the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 13930, the user includes at
least one entity. In one embodiment 13940, the entity includes at
least one person, or computer. In one embodiment 13950, the user
readable display includes a human readable display. In one
embodiment 13960, the user readable display includes one or more
active displays. In one embodiment 13970, the user readable display
includes one or more passive displays. In one embodiment 13980, the
user readable display includes one or more of a numeric format,
graphical format, or audio format. In one embodiment 13990, the
user readable display includes one or more of a display of one or
more differences in the comparison of at least one value related to
the first input and at least one value related to at least one
property of the at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device. In one
embodiment 13995, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device.
[1142] As illustrated in FIGS. 141-147, a computer-implemented
method 14100 comprises 14110 accepting a first input associated
with at least one parameter for making at least one frozen particle
composition or frozen piercing implement; 14120 accepting a second
input associated with at least one parameter for administering the
at least one frozen particle composition or frozen piercing
implement to at least one substrate; and 14160 processing results
of the first input and the second input. In one embodiment, 14130
wherein the at least one frozen particle composition or frozen
piercing implement includes at least one agent. In one embodiment,
14140 wherein the at least one agent includes one or more of a
therapeutic agent, adhesive agent, abrasive, reinforcement agent,
explosive material, or biological remodeling agent. In one
embodiment, 14150 the at least one substrate includes one or more
of a cell, tissue, organ, structure, or device.
[1143] In one embodiment, 14170 processing results of the first
input and the second input includes electronically processing
results of the first input and the second input. In one embodiment,
14180 electronically processing results of the first input and the
second input by utilizing one or more of Gaussian smoothing,
scaling, homomorphic filtering, parametric estimation techniques,
Boolean operations, Monte Carlo simulations, wavelet based
techniques, mirroring, smoothing, gradient weighted partial
differential equation smoothing, NURBS, polygonal modeling, splines
and patches modeling, algorithmic execution, logical
decision-making, result prediction, Finite Element Analysis, or
modification of a CAD design.
[1144] In one embodiment, 14210 the first input includes one or
more values related to the at least one parameter for making the at
least one frozen particle composition or frozen piercing implement.
In one embodiment, 14220 the first input includes one or more
values derived from at least one image of at least one frozen
particle composition or frozen piercing implement. In one
embodiment, 14230 the at least one image includes one or more
images acquired by at least one of laser, holography, x-ray,
crystallography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment, 14250 the at least one
parameter for making the at least one frozen particle composition
or frozen piercing implement includes one or more property
including: constitution of the at least one frozen particle
composition or frozen piercing implement, configuration of the at
least one frozen particle composition or frozen piercing implement,
formulation of the at least one frozen particle composition or
frozen piercing implement, size of the at least one frozen particle
composition or frozen piercing implement, density of the at least
one frozen particle composition or frozen piercing implement, shape
of the at least one frozen particle composition or frozen piercing
implement, physical structure of the at least one frozen particle
composition or frozen piercing implement, or physical or chemical
integrity of the at least one frozen particle composition or frozen
piercing implement. In one embodiment, 14310 the at least one
parameter for administering at least one frozen particle
composition or frozen piercing implement to at least one substrate
includes one or more of: substrate type; substrate function;
substrate size; substrate constitution; substrate architecture;
substrate durability; substrate temperature; temperature of
administration conditions; depth of administration of the at least
one frozen particle composition or frozen piercing implement;
substrate source; one or more temporal coordinates; one or more
spatial coordinates; presence or absence of at least one agent;
presence or absence of one or more sensors, valves, gates,
channels, transducers, circuits, nanoparticles, microactuators,
microdetectors, microheaters, or detection materials; angle of
administration of the at least one frozen particle composition or
frozen piercing implement; velocity of administration of the at
least one frozen particle composition or frozen piercing implement;
quantity of frozen particle compositions or frozen piercing
implements administered; rate of administration of more than one
frozen particle compositions or frozen piercing implements; method
of administration of at least one frozen particle composition or
frozen piercing implement; timing of administration of at least one
frozen particle composition or frozen piercing implement; or rate
of delivery of at least one agent.
[1145] In one embodiment, 14330 the at least one biological tissue
is located in at least one of in situ, in vitro, in vivo, in utero,
in planta, in silico, or ex vivo. In one embodiment, 14340 the at
least one substrate is at least partially located in at least one
subject. In one embodiment, 14350 the method further comprises
accepting a third input associated with at least one feature of the
at least one subject. In one embodiment, 14360 the at least one
feature of the at least one subject includes one or more of age,
gender, genotype, phenotype, proteomic profile, lipidomic profile,
glycomic profile, system biology profile, circulatory condition,
respiratory condition, blood condition, lymph condition, anatomic
landscape, body contour, or health condition.
[1146] In one embodiment, 14410 the at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement includes at least one parameter relating to
administering at least one of a therapeutic agent, adhesive agent,
biological remodeling agent, reinforcement agent, abrasive, or
explosive material by way of the at least one frozen particle
composition or frozen piercing implement.
[1147] In one embodiment, 14420 the at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement includes at least one parameter relating to at
least partially ablating or at least partially abrading one or more
surfaces of the at least one substrate with the at least one frozen
particle composition or frozen piercing implement. In one
embodiment, 14430 the processing results of the first input and the
second input includes determining at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement from one or more values derived from at least
one image of the at least one frozen particle composition or frozen
piercing implement. In one embodiment, 14440 the second input
includes one or more values related to the at least one parameter
for administering at least one frozen particle composition or
frozen piercing implement. In one embodiment, 14450 the one or more
values related to the at least one parameter for administering at
least one frozen particle composition or frozen piercing implement
includes one or more predictive values.
[1148] In one embodiment, 14460 the processing results includes
comparing at least one value related to the first input associated
with the at least one parameter for making the at least one frozen
particle composition or frozen piercing implement with at least one
value related to at least one property of the frozen particle
composition or frozen piercing implement. In one embodiment, 14470
the processing results includes determining one or more differences
in at least one value related to the first input and at least one
value related to at least one image of the at least one frozen
particle composition or frozen piercing implement.
[1149] In one embodiment, 14510 the processing results includes
determining one or more differences in at least one value related
to the second input associated with the at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement. In one embodiment, 14520 the processing results
includes generating one or more protocols for administering the at
least one frozen particle composition or frozen piercing implement.
In one embodiment, 14530 the administering at least one frozen
particle composition or frozen piercing implement to at least one
substrate includes delivering at least one agent to at least one
substrate.
[1150] In one embodiment, 14550, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment, 14560
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing
implement.
[1151] In one embodiment, 14570 the user includes at least one
entity. In one embodiment 14575, the entity includes at least one
person, or computer. In one embodiment 14580, the user readable
display includes a human readable display. In one embodiment 14590,
the user readable display includes one or more active displays. In
one embodiment 14595, the user readable display includes one or
more passive displays.
[1152] In one embodiment, 14598 the user readable display includes
one or more of a numeric format, graphical format, or audio
format.
[1153] In one embodiment, 14610 the user readable display includes
one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment, 14615 the user readable display includes one or
more displays of one or more differences in the comparison of at
least one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition or frozen piercing
implement.
[1154] In one embodiment 14618, the method further comprises
transmitting one or more signals that include information related
to the processing results of the first input and the second input.
In one embodiment, 14620 the transmitting one or more signals
includes transmitting one or more signals associated with selection
of at least one parameter for making at least one frozen particle
composition or frozen piercing implement. In one embodiment, 14630
the transmitting one or more signals includes transmitting one or
more signals associated with selection of at least one parameter
for making the at least one frozen particle composition or frozen
piercing implement. In one embodiment, 14640 the transmitting one
or more signals includes transmitting one or more signals
associated with comparing the information related to the processing
results of the first input and the second input. In one embodiment,
14650 the at least one frozen particle composition or frozen
piercing implement includes one or more of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1155] In one embodiment 14710, the method further comprises making
at least one frozen particle composition or frozen piercing
implement. In one embodiment, the method 14720 further comprises
administering at least one frozen particle composition or frozen
piercing implement to at least one substrate. In one embodiment,
14730 the method further comprises evaluating the at least one
substrate for one or more indicators related to at least one
parameter for administering the at least one frozen particle
composition or frozen piercing implement. In one embodiment, 14740
wherein the evaluating at least one substrate for one or more
indicators includes evaluating at least one of an assay, image, or
gross assessment of the at least one substrate prior to, during, or
subsequent to at least one administration of the at least one
frozen particle composition or frozen piercing implement. In one
embodiment, 14750 the assay includes at least one technique
including spectroscopy, microscopy, electrochemical detection,
polynucleotide detection, histological examination, biopsy
analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay.
[1156] In one embodiment 14755 the at least one image includes one
or more images acquired by at least one of a laser, holography,
x-ray crystallography, optical coherence tomography,
computer-assisted tomography scan, computed tomography, magnetic
resonance imaging, positron-emission tomography scan, ultrasound,
x-ray, electrical-impedance monitoring, microscopy, spectrometry,
flow cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation.
[1157] In one embodiment, 14760 the method further comprises
transmitting one or more signals that include information relating
to the accepting a first input or a second input and information
related to the evaluating the at least one substrate. In one
embodiment, 14770 the transmitting one or more signals includes
transmitting one or more signals associated with selection of at
least one parameter for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment, 14780
the transmitting one or more signals includes transmitting one or
more signals associated with selection of at least one parameter
for administering the at least one frozen particle composition or
frozen piercing implement.
[1158] As illustrated in FIGS. 148-150, in one embodiment, a
computer-implemented method 14800, comprises 14810 receiving one or
more signals that include information related to accepting input
associated with at least one parameter for making or administering
at least one frozen particle composition or frozen piercing
implement to at least one substrate; 14820 receiving one or more
signals that include information related to evaluating the at least
one substrate for one or more indicators of administration of the
at least one frozen particle composition, or frozen piercing
implement; and 14830 processing the information related to the
input associated with at least one parameter for making or
administering the at least one frozen particle composition or
frozen piercing implement to at least one substrate and the
information related to the evaluating the at least one
substrate.
[1159] In one embodiment, 14840 the at least one frozen particle
composition or frozen piercing implement includes at least one
agent. In one embodiment, 14850 wherein the evaluating at least one
substrate for one or more indicators includes evaluating at least
one of an assay, image, or gross assessment of the at least one
substrate prior to, during, or subsequent to at least one
administration of at least one frozen particle composition or
frozen piercing implement. In one embodiment, 14860 wherein the
assay includes at least one technique that includes spectroscopy,
microscopy, electrochemical detection, polynucleotide detection,
histological examination, biopsy analysis, fluorescence resonance
energy transfer, electron transfer, enzyme assay, electrical
conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay. In one
embodiment, 14870 wherein the image includes at least one image
acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation.
[1160] In one embodiment, 14910 wherein the input associated with
at least one parameter for administering at least one frozen
particle composition or frozen piercing implement to at least one
substrate includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunable lens, sensor, regulator, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, energy source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen particle composition or frozen piercing implement;
velocity of administration of the at least one frozen particle
composition or frozen piercing implement; quantity of frozen
particle compositions or frozen piercing implements administered;
rate of administration of more than one frozen particle
compositions or frozen piercing implements; method of
administration of at least one frozen particle composition or
frozen piercing implement; timing of administration of at least one
frozen particle composition or frozen piercing implement; or rate
of delivery of at least one agent.
[1161] In one embodiment, 14920 wherein the input associated with
at least one parameter for making the at least one frozen particle
composition or frozen piercing implement includes one or more
property including: constitution of the at least one frozen
particle composition or frozen piercing implement, formulation of
the at least one frozen particle composition or frozen piercing
implement, size of the at least one frozen particle composition or
frozen piercing implement, density of the at least one frozen
particle composition or frozen piercing implement, shape of the at
least one frozen particle composition or frozen piercing implement,
physical structure of the at least one frozen particle composition
or frozen piercing implement, or physical or chemical integrity of
the at least one frozen particle composition or frozen piercing
implement.
[1162] In one embodiment, 15010 the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment, 15020 the receiving one or more signals
includes receiving one or more signals associated with selection of
at least one parameter for making or administering the at least one
frozen particle composition or frozen piercing implement. In one
embodiment, 15030 wherein the at least one substrate includes one
or more of a cell, tissue, organ, structure, device, or food
product. In one embodiment, 15040 wherein the at least one frozen
particle composition or frozen piercing implement includes one or
more of hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon,
xenon, chlorine, bromine, carbon dioxide, acetone, ethyl acetate,
dimethyl sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1163] In one embodiment 15050, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 15055
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 15060, the user includes at least one entity. In
one embodiment 15065, the entity includes at least one person, or
computer. In one embodiment 15070, the user readable display
includes a human readable display. In one embodiment 15080, the
user readable display includes one or more active displays. In one
embodiment 15090, the user readable display includes one or more
passive displays. In one embodiment 15095, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 15096 the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to th first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 15097, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
[1164] As illustrated in FIGS. 151-157, in one embodiment, a
computer-implemented method 15100 comprises 15110 accepting a first
input associated with at least one parameter for making at least
one frozen piercing implement device; 15120 accepting a second
input associated with at least one parameter for administering the
at least one frozen piercing implement device to at least one
substrate; 15180 processing results of the first input and the
second input; and 15198 generating an output to a user readable
display. In one embodiment, 15125 the at least one substrate
includes one or more of a cell, tissue, organ, structure, device or
food product. In one embodiment, 15130 the at least one frozen
piercing implement device includes at least one of a frozen
piercing implement array device, frozen piercing implement fluidic
device, or frozen piercing implement injection device. In one
embodiment, 15140 the frozen piercing implement injection device
includes a frozen piercing implement auto-injection device. In one
embodiment, 15150 wherein the at least one frozen piercing
implement device includes at least one agent. In one embodiment,
15160 wherein the at least one agent includes one or more of a
therapeutic agent, adhesive agent, abrasive, reinforcement agent,
explosive material, or biological remodeling agent. In one
embodiment, 15170 wherein the at least one agent is located in at
least one frozen piercing implement of the device. In one
embodiment, 15190 processing results of the first input and the
second input includes electronically processing results of the
first input and the second input. In one embodiment, 15195
electronically processing results of the first input and the second
input by utilizing one or more of Gaussian smoothing, scaling,
homomorphic filtering, parametric estimation techniques, Boolean
operations, Monte Carlo simulations, wavelet based techniques,
mirroring, smoothing, gradient weighted partial differential
equation smoothing, NURBS, polygonal modeling, splines and patches
modeling, algorithmic execution, logical decision-making, result
prediction, Finite Element Analysis, or modification of a CAD
design.
[1165] In one embodiment, 15210 the first input includes one or
more values related to the at least one parameter for making the at
least one frozen piercing implement device. In one embodiment,
15220 wherein the at least one parameter for making the at least
one frozen piercing implement device includes one or more of:
constitution of the at least one frozen piercing implement of the
frozen piercing implement device, constitution of the at least one
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, physical or chemical integrity of the at least
one frozen piercing implement device, or presence or absence of at
least one microparticle, nanoparticle, lens, tunable lens, sensor,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, energy source, injector, controller,
receiver, transmitter, or circuit, in the at least one frozen
piercing implement or frozen piercing implement device. In one
embodiment, 15230 the at least one parameter for administering at
least one frozen piercing implement device to at least one
substrate includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunable lens, sensor, regulator, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, energy source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
[1166] In one embodiment, 15310 the one or more values related to
the at least one parameter for administering at least one frozen
piercing implement device includes one or more predictive values.
In one embodiment, 15320 the at least one parameter for
administering at least one frozen piercing implement device
includes at least one parameter relating to at least partially
ablating or at least partially abrading one or more surfaces of the
at least one substrate with the at least one frozen piercing
implement device. In one embodiment, 15330 the first input includes
one or more values derived from at least one property of at least
one frozen piercing implement device. In one embodiment, 15340 the
at least one substrate is located in at least one of in situ, in
vitro, in vivo, in utero, in planta, in silico, or ex vivo. In one
embodiment, 15350 the at least one substrate is at least partially
located in at least one subject. In one embodiment, the method
15360 further comprises accepting a third input associated with at
least one feature of the at least one subject. In one embodiment,
the at least one feature of the at least one subject includes one
or more of age, gender, genotype, phenotype, proteomic profile,
anatomic landscape, body contour, or health condition. In one
embodiment 15370, the at least one feature of the at least one
subject includes one or more of age, gender, genotype, phenotype,
proteomic profile, lipidomic profile, glycomic profile, system
biology profile, lymph condition, circulatory condition,
respiratory condition, blood condition, anatomic landscape, body
contour, or health condition. In one embodiment, 15380 the output
includes one or more instructions for making the at least one
frozen particle composition or frozen piercing implement. In one
embodiment, 15390 the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement.
[1167] In one embodiment 15407, the user readable display includes
one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 15408, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement. In one embodiment, 15410 the processing results of the
first input and the second input includes determining at least one
parameter for making at least one frozen piercing implement device
from one or more values derived from at least one characteristic of
at least one frozen piercing implement of the frozen piercing
implement device. In one embodiment, 15420 the second input
includes one or more values related to the at least one parameter
for administering at least one frozen piercing implement device to
the at least one substrate. In one embodiment, 15430 the processing
results includes comparing at least one value related to the first
input associated with the at least one parameter for making the
frozen piercing implement device with at least one value related to
at least one property of the at least one frozen piercing
implement. In one embodiment, 15440 the processing results includes
determining one or more differences in at least one value related
to the first input and at least one value related to at least one
property of the at least one frozen piercing implement device. In
one embodiment, 15450 the processing results includes determining
one or more differences in at least one value related to the second
input associated with the one or more parameters of administering
at least one frozen piercing implement device to the at least one
substrate. In one embodiment, 15460 the processing results includes
generating one or more protocols for administering the at least one
frozen piercing implement device. In one embodiment, 15510 the
administering at least one frozen piercing implement device
includes delivering at least one agent to the at least one
substrate by way of the at least one frozen piercing implement
device.
[1168] In one embodiment 15518, the user includes at least one
entity. In one embodiment 15520, the entity includes at least one
person, or computer. In one embodiment 15530, the user readable
display includes a human readable display. In one embodiment 15540,
the user readable display includes one or more active displays. In
one embodiment 15550, the user readable display includes one or
more passive displays.
[1169] In one embodiment 15560, the user readable display includes
one or more of a numeric format, graphical format, or audio format.
In one embodiment 15570 the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to th first input and at least one value
related to at least one property of the at least one frozen
particle composition or frozen piercing implement. In one
embodiment 15580, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition or frozen piercing
implement.
[1170] In one embodiment, the method 15610 further comprises
transmitting one or more signals that include information related
to the processing results of the first input and the second input.
In one embodiment, 15620 the transmitting one or more signals
includes transmitting one or more signals associated with selection
of at least one parameter for making the at least one frozen
piercing implement device. In one embodiment, 15630 the
transmitting one or more signals includes transmitting one or more
signals associated with selection of one or more agents to be
delivered by the at least one frozen piercing implement device. In
one embodiment, 15640 wherein the transmitting one or more signals
includes transmitting one or more signals associated with comparing
the information related to the processing results of the first
input and the second input. In one embodiment, 15650 wherein the at
least one frozen piercing implement device includes one or more
frozen piercing implements that include at least one of hydrogen
oxide, nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1171] In one embodiment, the method 15710 further comprises making
at least one frozen piercing implement device. In one embodiment,
the method 15720 further comprises administering at least one
frozen piercing implement device to at least one substrate. In one
embodiment, the method 15730 further comprises evaluating the at
least one substrate for one or more indicators related to at least
one parameter for administering the at least one frozen piercing
implement device. In one embodiment, 15740 the evaluating at least
one substrate for one or more indicators includes evaluating at
least one of an assay, image, or gross assessment of the at least
one substrate prior to, during, or subsequent to at least one
administration of the at least one frozen piercing implement
device. In one embodiment, 15750 the assay includes at least one
technique including spectroscopy, microscopy, electrochemical
detection, polynucleotide detection, histological examination,
biopsy analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment,15755 wherein the at least one
image includes one or more images acquired by at least one of
laser, holography, x-ray, crystallography, optical coherence
tomography, computer-assisted tomography scan, computed tomography,
magnetic resonance imaging, positron-emission tomography scan,
ultrasound, x-ray, electrical-impedance monitoring, microscopy,
spectrometry, flow cytommetry, radioisotope imaging, thermal
imaging, infrared visualization, multiphoton calcium-imaging,
photography, or in silico generation
[1172] In one embodiment, the method 15760 further comprises
transmitting one or more signals that include information relating
to the accepting a first input or a second input and information
related to the evaluating the at least one substrate. In one
embodiment, 15770 the transmitting one or more signals includes
transmitting one or more signals associated with selection of at
least one parameter for making the at least one frozen piercing
implement device. In one embodiment, 15780 wherein the transmitting
one or more signals includes transmitting one or more signals
associated with selection of at least one parameter for
administering the at least one frozen piercing implement
device.
[1173] As illustrated in FIGS. 158-160 a computer-implemented
method 15800 comprises 15810 receiving one or more signals that
include information related to accepting input associated with at
least one parameter for making or administering at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate; wherein the at least
one frozen particle composition, frozen piercing implement, or
frozen piercing implement device includes at least one agent; 15820
receiving one or more signals that include information related to
evaluating the at least one substrate for one or more indicators of
administration of the at least one frozen particle composition,
frozen piercing implement, frozen piercing implement device, or
agent; and 15830 processing the information related to the input
associated with at least one parameter for making or administering
the at least one frozen piercing implement device to at least one
substrate and the information related to the evaluating the at
least one substrate. In one embodiment, 15840 wherein the
evaluating at least one substrate for one or more indicators
includes evaluating at least one of an assay, image, or gross
assessment of the at least one substrate prior to, during, or
subsequent to at least one administration of at least one frozen
piercing implement device. In one embodiment, 15850 the assay
includes at least one technique that includes spectroscopy,
microscopy, electrochemical detection, polynucleotide detection,
histological examination, biopsy analysis, fluorescence resonance
energy transfer, electron transfer, enzyme assay, electrical
conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay. In one
embodiment, 15860 wherein the image includes at least one image
acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment, 15870 wherein the receiving
one or more signals includes receiving one or more signals
associated with selection of at least one parameter for making or
administering the at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device.
[1174] In one embodiment, 15910 the at least one parameter for
making the at least one frozen piercing implement device includes
one or more of: constitution of the at least one frozen piercing
implement of the frozen piercing implement device, constitution of
the at least one frozen piercing implement device, formulation of
the at least one frozen piercing implement of the frozen piercing
implement device, formulation of the at least one frozen piercing
implement device, size of the at least one frozen piercing
implement of the frozen piercing implement device, size of the at
least one frozen piercing implement device, shape of the at least
one frozen piercing implement of the frozen piercing implement
device, shape of the at least one frozen piercing implement device,
physical structure of the at least one frozen piercing implement of
the frozen piercing implement device, physical structure of the at
least one frozen piercing implement device, physical or chemical
integrity of the at least one frozen piercing implement of the
frozen piercing implement device, physical or chemical integrity of
the at least one frozen piercing implement device, or presence or
absence of at least one microparticle, nanoparticle, lens, tunable
lens, sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, energy source, injector,
controller, receiver, transmitter, or circuit, in the at least one
frozen piercing implement or frozen piercing implement device.
[1175] In one embodiment, 15920 wherein the at least one parameter
for administering at least one frozen piercing implement device to
at least one substrate includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunable lens, sensor, regulator,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, energy source, injector, controller,
receiver, transmitter, or circuit; angle of administration of the
at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
[1176] In one embodiment, 16010 the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment, 16020 wherein the at least one substrate
includes one or more of a cell, tissue, organ, structure, device,
or food product.
[1177] In one embodiment, 16030 wherein the at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device includes one or more of hydrogen oxide, nitrogen,
oxygen, air, helium, neon, argon, xenon, chlorine, bromine, carbon
dioxide, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl
formamide, dioxane, tetrahydrofuran, acetronitrile, acetic acid,
n-butanol, isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, standard saline citrate, methane, toluene, chloroform,
polyethylene glycol, acetic acid, Ringer's solution, lactated
Ringer's solution, Hartmann's solution, acetated Ringer's solution,
phosphate buffered solution, TRIS-buffered saline solution, Hank's
balanced salt solution, Earle's balanced salt solution, standard
saline citrate, HEPES-buffered saline, dextrose, glucose, or
diethyl ether.
[1178] In one embodiment 16035, the output includes one or more
instructions for making the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 16040, the output includes at
least one graphical description of the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device.
[1179] In one embodiment 16050, the user includes at least one
entity. In one embodiment 16055, the entity includes at least one
person, or computer. In one embodiment 16060, the user readable
display includes a human readable display. In one embodiment 16065,
the user readable display includes one or more active displays. In
one embodiment 16070, the user readable display includes one or
more passive displays. In one embodiment 16075, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 16076 the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to th first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 16077, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
[1180] In one embodiment 16110, at least one parameter for making
the at least one frozen particle composition or frozen piercing
implement includes one or more of: constitution of the at least one
frozen particle composition or frozen piercing implement,
formulation of the at least one frozen particle composition or
frozen piercing implement, size of the at least one frozen particle
composition or frozen piercing implement, density of the at least
one frozen particle composition or frozen piercing implement, shape
of the at least one frozen particle composition or frozen piercing
implement, physical structure of the at least one frozen particle
composition or frozen piercing implement, physical or chemical
integrity of the at least one frozen particle composition or frozen
piercing implement, or presence or absence of a microparticle,
nanoparticle, lens, tunable lens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
energy source, injector, controller, receiver, transmitter, or
circuit.
[1181] In one embodiment 16120, at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
[1182] As illustrated in FIG. 162, in one embodiment, a method
16200 comprises 16210 making at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device; and 16220 administering at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate. In one embodiment, the
method 16200 includes a computer-implemented method.
[1183] As illustrated in FIGS. 163-166, a system 16300 comprises:
16310 means for receiving one or more signals that include
information related to accepting input associated with at least one
parameter for making or administering at least one frozen particle
composition or frozen piercing implement to at least one substrate,
the frozen particle composition or frozen piercing implement
including at least one agent; 16320 means for receiving one or more
signals that include information related to evaluating the at least
one substrate for one or more indicators of administration of the
at least one frozen particle composition, frozen piercing
implement, or agent; 16330 means for processing the information
related to the input associated with at least one parameter for
making or administering the at least one frozen particle
composition or frozen piercing implement to at least one substrate
and the information related to the evaluating the at least one
substrate; and 16340 means for generating an output to a user
readable display. In one embodiment 16350, evaluating at least one
substrate for one or more indicators includes evaluating at least
one of an assay, image, or gross assessment of the at least one
biological tissue prior to, during, or subsequent to at least one
administration of the at least one frozen particle composition or
frozen piercing implement. In one embodiment 16360, the assay
includes at least one technique that includes spectroscopy,
microscopy, electrochemical detection, polynucleotide detection,
histological examination, biopsy analysis, fluorescence resonance
energy transfer, electron transfer, enzyme assay, electrical
conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay.
[1184] In one embodiment 16370, the image includes at least one
image acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment 16410, the input associated
with at least one parameter for administering at least one frozen
particle composition or frozen piercing implement to at least one
substrate includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
particle composition or frozen piercing implement; force of
administration of the at least one frozen particle composition or
frozen piercing implement; velocity of administration of the at
least one frozen particle composition or frozen piercing implement;
quantity of frozen particle compositions or frozen piercing
implements administered; rate of administration of more than one
frozen particle compositions or frozen piercing implements; method
of administration of at least one frozen particle composition or
frozen piercing implement; timing of administration of at least one
frozen particle composition or frozen piercing implement; or rate
of delivery of at least one agent.
[1185] In one embodiment 16420, the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 16430, the means for receiving one or more
signals includes means for receiving one or more signals associated
with selection of at least one parameter for making the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 16440, the at least one parameter for making the at
least one frozen particle composition or frozen piercing implement
includes one or more property including: constitution of the at
least one frozen particle composition or frozen piercing implement,
configuration of the at least one frozen particle composition or
frozen piercing implement, formulation of the at least one frozen
particle composition or frozen piercing implement, size of the at
least one frozen particle composition or frozen piercing implement,
density of the at least one frozen particle composition or frozen
piercing implement, shape of the at least one frozen particle
composition or frozen piercing implement, physical structure of the
at least one frozen particle composition or frozen piercing
implement, physical or chemical integrity of the at least one
frozen particle composition or frozen piercing implement.
[1186] In one embodiment 16510, the at least one substrate includes
one or more of a cell, tissue, organ, structure, device, or food
product. In one embodiment 16520, the at least one frozen particle
composition or frozen piercing implement includes one or more of
hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, methane, toluene,
chloroform, polyethylene glycol, acetic acid, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether.
[1187] In one embodiment 16530, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 16540,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 16550, the user includes at least one entity. In
one embodiment 16560, the entity includes at least one person, or
computer. In one embodiment 16570, the user readable display
includes a human readable display. In one embodiment 16580, the
user readable display includes one or more active displays. In one
embodiment 16590, the user readable display includes one or more
passive displays. In one embodiment 16595, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 16610, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 16620, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
[1188] As illustrated in FIGS. 167-174, a system 16700 comprises:
16710 means for accepting a first input associated with at least
one parameter for making at least one frozen piercing implement
device; 16720 means for accepting a second input associated with at
least one parameter for administering the at least one frozen
piercing implement device to at least one substrate; 16730 means
for processing the first input and the second input; and 16740
means for generating an output to a user readable display.
[1189] In one embodiment 16750, the at least one frozen piercing
implement device includes at least one of a frozen piercing
implement array device, frozen piercing implement fluidic device,
or frozen piercing implement injection device. In one embodiment
16760, the frozen piercing implement injection device includes a
frozen piercing implement auto-injection device.
[1190] In one embodiment 16770, the means for processing the first
input and the second input includes means for electronically
processing the first input and the second input. In one embodiment
16780, the means for processing the first input and the second
input includes means for electronically processing the first input
and the second input by utilizing one or more of Gaussian
smoothing, scaling, homomorphic filtering, parametric estimation
techniques, Boolean operations, Monte Carlo simulations, wavelet
based techniques, mirroring, smoothing, gradient weighted partial
differential equation smoothing, NURBS, polygonal modeling, splines
and patches modeling, algorithmic execution, logical
decision-making, result prediction, Finite Element Analysis, or
modification of a CAD design.
[1191] In one embodiment 16810, the frozen piercing implement
device includes at least one agent. In one embodiment 16820, the at
least one agent is located in at least one frozen piercing
implement of the device. In one embodiment 16830, the at least one
agent includes one or more of a therapeutic agent, adhesive agent,
abrasive, reinforcement agent, explosive material, or biological
remodeling agent. In one embodiment 16840, the at least one
substrate includes one or more of a cell, tissue, organ, structure,
device, or food product. In one embodiment 16850, the first input
includes one or more values related to the at least one parameter
for making the at least one frozen piercing implement device. In
one embodiment 16860, the at least one parameter for making the at
least one frozen piercing implement device includes one or more of:
constitution of the at least one frozen piercing implement of the
frozen piercing implement device, constitution of the at least one
frozen piercing implement device, configuration of the at least one
frozen piercing implement, configuration of the at least one frozen
piercing implement or frozen piercing implement device, formulation
of the at least one frozen piercing implement of the frozen
piercing implement device, formulation of the at least one frozen
piercing implement device, size of the at least one frozen piercing
implement of the frozen piercing implement device, size of the at
least one frozen piercing implement device, shape of the at least
one frozen piercing implement of the frozen piercing implement
device, shape of the at least one frozen piercing implement device,
physical structure of the at least one frozen piercing implement of
the frozen piercing implement device, physical structure of the at
least one frozen piercing implement device, physical or chemical
integrity of the at least one frozen piercing implement of the
frozen piercing implement device, or physical or chemical integrity
of the at least one frozen piercing implement device.
[1192] In one embodiment 16910, the at least one parameter for
administering at least one frozen piercing implement device to at
least one substrate includes one or more of substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
[1193] In one embodiment 16920, the at least one parameter for
administering at least one frozen piercing implement device
includes at least one parameter relating to at least partially
ablating or at least partially abrading one or more surfaces of the
at least one substrate with the at least one frozen piercing
implement device. In one embodiment 16930, the first input includes
one or more values derived from at least one property of at least
one frozen piercing implement device. In one embodiment 16940, the
at least one substrate is located in at least one of in situ, in
vitro, in vivo, in utero, in planta, in silico, or ex vivo. In one
embodiment 16950, the at least one substrate is at least partially
located in at least one subject.
[1194] In one embodiment 16960, the system further comprises means
for accepting a third input associated with at least one feature of
the at least one subject. In one embodiment 17010, the at least one
feature of the at least one subject includes one or more of age,
gender, genotype, phenotype, proteomic profile, lipidomic profile,
glycomic profile, system biology profile, lymph condition,
circulatory condition, respiratory condition, blood condition,
anatomic landscape, body contour, or health condition. In one
embodiment 17020, the means for processing the first input and the
second input includes means for determining at least one parameter
for administering at least one frozen piercing implement device
from one or more values derived from at least one image of at least
one frozen piercing implement of the device, or at least one image
of at least one frozen piercing implement device. In one embodiment
17030, the second input includes one or more values related to the
at least one parameter for administering at least one frozen
piercing implement device to the at least one substrate.
[1195] In one embodiment 17040, the one or more values related to
the at least one parameter for administering at least one frozen
piercing implement device includes one or more predictive values.
In one embodiment 17050, the means for processing the first input
and the second input includes means for comparing at least one
value related to the first input associated with the at least one
parameter for making the frozen piercing implement device with at
least one value related to at least one property of at least one
frozen piercing implement of the device, or at least one frozen
piercing implement device. In one embodiment 17060, the means for
processing the first input and the second input includes means for
determining one or more differences in at least one value related
to the first input and at least one value related to at least one
property of at least one frozen piercing implement device or at
least one frozen piercing implement of the device. In one
embodiment 17070, the means for processing the first input and the
second input includes means for determining one or more differences
in at least one value related to the second input associated with
the one or more parameters of administering at least one frozen
piercing implement device to the at least one substrate.
[1196] In one embodiment 17110, the means for processing the first
input and the second input includes means for generating one or
more protocols for administering the at least one frozen piercing
implement device. In one embodiment 17120, the output includes one
or more instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 17130,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing
implement.
[1197] In one embodiment 17140, the user includes at least one
entity. In one embodiment 17150, the entity includes at least one
person, or computer. In one embodiment 17160, the user readable
display includes a human readable display. In one embodiment 17170,
the user readable display includes one or more active displays. In
one embodiment 17180, the user readable display includes one or
more passive displays. In one embodiment 17185, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 17190, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement.
[1198] In one embodiment 17210, the user readable display includes
one or more of a display of one or more differences in the
comparison of at least one value related to the second input and at
least one value related to at least one parameter for
administration of the at least one frozen particle composition or
frozen piercing implement. In one embodiment 17220, the system
further comprises means for transmitting one or more signals that
include information related to the means for processing the first
input and the second input. In one embodiment 17230, the means for
transmitting one or more signals includes means for transmitting
one or more signals associated with selection of at least one
parameter for making the at least one frozen piercing implement
device. In one embodiment 17240, the means for transmitting one or
more signals includes means for transmitting one or more signals
associated with selection of one or more agents to be delivered by
the at least one frozen piercing implement device.
[1199] In one embodiment 17250, the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 17310, the means for transmitting one or
more signals includes means for transmitting one or more signals
associated with at least one parameter for making or administering
at least one frozen piercing implement device. In one embodiment
17320, means for transmitting one or more signals includes means
for transmitting one or more signals associated with means for
comparing the information related to the means for processing the
first input and the second input. In one embodiment 17330, the at
least one frozen piercing implement device includes one or more
frozen piercing implements that include at least one of hydrogen
oxide, nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, methane, toluene,
chloroform, polyethylene glycol, acetic acid, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether.
[1200] In one embodiment 17340, the system further comprises means
for making at least one frozen piercing implement device. In one
embodiment 17350, the system further comprises means for
administering at least one frozen piercing implement device to at
least one substrate. In one embodiment 17360, the system further
comprises means for evaluating the at least one substrate for one
or more indicators related to at least one parameter for
administering the at least one frozen piercing implement device. In
one embodiment 17370, the means for evaluating at least one
substrate for one or more indicators includes means for evaluating
at least one of an assay, image, or gross assessment of the at
least one substrate prior to, during, or subsequent to at least one
administration of the at least one frozen particle composition or
frozen piercing implement.
[1201] In one embodiment 17410, the assay includes at least one
technique including spectroscopy, microscopy, electrochemical
detection, polynucleotide detection, histological examination,
biopsy analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment 17420, the at least one image
includes one or more images acquired by at least one of laser,
holography, x-ray crystallography, optical coherence tomography,
computer-assisted tomography scan, computed tomography, magnetic
resonance imaging, positron-emission tomography scan, ultrasound,
x-ray, electrical-impedance monitoring, microscopy, spectrometry,
flow cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation.
[1202] In one embodiment 17430, the system further comprises means
for transmitting one or more signals that include information
relating to the accepting a first input or a second input and
information related to the evaluating the at least one substrate.
In one embodiment 17440, the means for transmitting one or more
signals includes means for transmitting one or more signals
associated with selection of at least one parameter for making the
at least one frozen particle composition or frozen piercing
implement. In one embodiment 17460, the means for transmitting one
or more signals includes means for transmitting one or more signals
associated with selection of at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement.
[1203] As illustrated in FIGS. 175-181, a system 17500, comprises:
17510 means for accepting a first input associated with at least
one parameter for making at least one frozen particle composition
or frozen piercing implement; 17520 means for accepting a second
input associated with at least one parameter for administering the
at least one frozen particle composition or frozen piercing
implement to at least one substrate; 17530 means for processing the
first input and the second input; and 17540 means for generating an
output to a user readable display. In one embodiment 17550, the at
least one parameter for administering at least one frozen particle
composition or frozen piercing implement includes at least one
parameter relating to at least partially ablating or at least
partially abrading one or more surfaces of the at least one
substrate with the at least one frozen particle composition or
frozen piercing implement. In one embodiment 17560, the means for
processing the first input and the second input includes means for
electronically processing the first input and the second input. In
one embodiment 17570, the means for processing the first input and
the second input includes means for electronically processing the
first input and the second input by utilizing one or more of
Gaussian smoothing, scaling, homomorphic filtering, parametric
estimation techniques, Boolean operations, Monte Carlo simulations,
wavelet based techniques, mirroring, smoothing, gradient weighted
partial differential equation smoothing, NURBS, polygonal modeling,
splines and patches modeling, algorithmic execution, logical
decision-making, result prediction, Finite Element Analysis, or
modification of a CAD design.
[1204] In one embodiment 17580, the first input includes one or
more values related to the at least one parameter for making the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 17610, the at least one parameter for making the
at least one frozen particle composition or frozen piercing
implement includes one or more property including: constitution of
the at least one frozen particle composition or frozen piercing
implement, configuration of the at least one frozen particle
composition or frozen piercing implement, formulation of the at
least one frozen particle composition or frozen piercing implement,
size of the at least one frozen particle composition or frozen
piercing implement, density of the at least one frozen particle
composition or frozen piercing implement, shape of the at least one
frozen particle composition or frozen piercing implement, physical
structure of the at least one frozen particle composition or frozen
piercing implement, physical or chemical integrity of the at least
one frozen particle composition or frozen piercing implement, or
presence or absence of a microparticle, nanoparticle, lens,
tunablelens, sensor, transducer, actuator, detector, heater, valve,
gate, channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit. In one embodiment
17620, the at least one parameter for administering at least one
frozen particle composition or frozen piercing implement to at
least one substrate includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of one or more sensors,
valves, gates, channels, transducers, circuits, nanoparticles,
microactuators, microdetectors, microheaters, or detection
materials; angle of administration of the at least one frozen
particle composition or frozen piercing implement; force of
administration of the at least one frozen particle composition or
frozen piercing implement velocity of administration of the at
least one frozen particle composition or frozen piercing implement;
quantity of frozen particle compositions or frozen piercing
implements administered; rate of administration of more than one
frozen particle compositions or frozen piercing implements; method
of administration of at least one frozen particle composition or
frozen piercing implement; timing of administration of at least one
frozen particle composition or frozen piercing implement; or rate
of delivery of at least one agent.
[1205] In one embodiment 17630, the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 17710, the at least one substrate includes
one or more of a cell, tissue, organ, structure, device, or food
product. In one embodiment 17720, the first input includes one or
more values derived from at least one property of the at least one
frozen particle composition or frozen piercing implement.
[1206] In one embodiment 17730, the at least one substrate is
located in at least one of in situ, in vitro, in vivo, in utero, in
planta, in silico, or ex vivo. In one embodiment 17740, the at
least one substrate is at least partially located in at least one
subject. In one embodiment 17750, the system further comprises
means for accepting a third input associated with at least one
feature of the at least one subject. In one embodiment 17760, the
at least one feature of the at least one subject includes one or
more of age, gender, genotype, phenotype, proteomic profile,
lipidomic profile, glycomic profile, system biology profile, lymph
condition, circulatory condition, respiratory condition, blood
condition, anatomic landscape, body contour, or health condition.
In one embodiment 17770, the means for processing the first input
and the second input includes means for determining at least one
parameter for administering at least one frozen particle
composition or frozen piercing implement from one or more values
derived from at least one parameter for administering the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 17780, the means for processing the first input and
the second input includes means for determining one or more
differences in at least one value related to the second input and
at least one value related to at least one parameter for
administering of at least one frozen particle composition or frozen
piercing implement to at least one substrate.
[1207] In one embodiment 17810, the second input includes one or
more values related to the at least one parameter for administering
at least one frozen particle composition or frozen piercing
implement to the at least one substrate. In one embodiment 17820,
the one or more values related to the at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement includes one or more predictive values. In one
embodiment 17830, the means for processing the first input and the
second input includes means for comparing at least one value
related to the first input associated with the at least one
parameter for making the at least one frozen particle composition
or frozen piercing implement with at least one value related to at
least one property of the frozen particle composition or frozen
piercing implement.
[1208] In one embodiment 17840, the means for processing the first
input and the second input includes means for determining one or
more differences in at least one value related to the first input
and at least one value related to at least one property of the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 19950, the means for processing the first input
and the second input includes means for generating one or more
protocols for administering the at least one frozen particle
composition or frozen piercing implement. In one embodiment 17860,
the output includes one or more instructions for making the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 17870, the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement. In one embodiment 17880, the user
includes at least one entity.
[1209] In one embodiment 17910, the entity includes at least one
person, or computer. In one embodiment 17920, the user readable
display includes a human readable display. In one embodiment 17930,
the user readable display includes one or more active displays.
[1210] In one embodiment 17940, the user readable display includes
one or more passive displays. In one embodiment 17950, the user
readable display includes one or more of a numeric format,
graphical format, or audio format. In one embodiment 17960, the
user readable display includes one or more of a display of one or
more differences in the comparison of at least one value related to
the first input and at least one value related to at least one
property of the at least one frozen particle composition or frozen
piercing implement. In one embodiment 17970, the user readable
display includes one or more of a display of one or more
differences in the comparison of at least one value related to the
second input and at least one value related to at least one
parameter for administration of the at least one frozen particle
composition or frozen piercing implement.
[1211] In one embodiment 17980, the system further comprises means
for transmitting one or more signals that include information
related to the processing of the first input and the second input.
In one embodiment 17990, the means for transmitting one or more
signals includes means for transmitting one or more signals
associated with selection of at least one parameter for making the
at least one frozen particle composition or frozen piercing
implement.
[1212] In one embodiment 18010, the means for transmitting one or
more signals includes means for transmitting one or more signals
associated with comparing the information related to the processing
of the first input and the second input. In one embodiment 18020,
the means for transmitting one or more signals includes means for
transmitting one or more signals associated with comparing the
information related to the processing of the first input and the
second input. In one embodiment 18030, the at least one frozen
particle composition or frozen piercing implement includes one or
more of hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon,
xenon, chlorine, bromine, carbon dioxide, acetone, ethyl acetate,
dimethyl sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, methane, toluene,
chloroform, polyethylene glycol, acetic acid, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether. In one embodiment 18040, the system
further comprises means for making at least one frozen particle
composition or frozen piercing implement. In one embodiment 18050,
the system further comprises means for administering at least one
frozen particle composition or frozen piercing implement to at
least one substrate. In one embodiment 18060, the system further
comprises means for evaluating the at least one substrate for one
or more indicators related to at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement. In one embodiment 18070, evaluating at
least one substrate for one or more indicators includes evaluating
at least one of an assay, image, or gross assessment of the at
least one substrate prior to, during, or subsequent to at least one
administration of the at least one frozen particle composition or
frozen piercing implement.
[1213] In one embodiment 18110, the assay includes at least one
technique including spectroscopy, microscopy, electrochemical
detection, polynucleotide detection, histological examination,
biopsy analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment 18120, the at least one image
includes one or more images acquired by at least one of laser,
holography, x-ray crystallography, optical coherence tomography,
computer-assisted tomography scan, computed tomography, magnetic
resonance imaging, positron-emission tomography scan, ultrasound,
x-ray, electrical-impedance monitoring, microscopy, spectrometry,
flow cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment 18130, the system further
comprises means for transmitting one or more signals that include
information relating to the accepting a first input or a second
input and information related to the evaluating the at least one
substrate. In one embodiment 18140, the means for transmitting one
or more signals includes means for transmitting one or more signals
associated with selection of at least one parameter for making the
at least one frozen particle composition or frozen piercing
implement. In one embodiment 18150, the means for transmitting one
or more signals includes means for transmitting one or more signals
associated with selection of at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement.
[1214] As illustrated in FIGS. 182-185, a system 18200 comprises:
18210 means for receiving one or more signals that include
information related to accepting input associated with at least one
parameter for making or administering at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate; wherein the at least
one frozen particle composition, frozen piercing implement, or
frozen piercing implement device includes at least one agent; 18220
means for receiving one or more signals that include information
related to evaluating the at least one substrate for one or more
indicators of administration of at least one frozen particle
composition, frozen piercing implement, frozen piercing implement
device, or agent; 18230 means for processing the information
related to the input associated with at least one parameter for
making or administering the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate and the information
related to the evaluating the at least one substrate; and 18240
means for generating an output to a user readable display. In one
embodiment 18250, the at least one frozen piercing implement device
includes at least one of a frozen piercing implement device, frozen
piercing implement fluidic device, or frozen piercing implement
injection device. In one embodiment 18260, the frozen piercing
implement injection device includes a frozen piercing implement
auto-injection device. In one embodiment 18270, evaluating at least
one substrate for one or more indicators includes means for
evaluating at least one of an assay, image, or gross assessment of
the at least one biological tissue prior to, during, or subsequent
to at least one administration of one or more frozen piercing
implement devices. In one embodiment 18280, the assay includes at
least one technique that includes spectroscopy, microscopy,
electrochemical detection, polynucleotide detection, histological
examination, biopsy analysis, fluorescence resonance energy
transfer, electron transfer, enzyme assay, electrical conductivity,
isoelectric focusing, chromatography, immunoprecipitation,
immunoseparation, aptamer binding, filtration, electrophoresis,
immunoassay, or radioactive assay.
[1215] In one embodiment 18310, the image includes at least one
image acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment 18320, the means for receiving
one or more signals includes means for receiving one or more
signals associated with selection of at least one parameter for
making or administering the at least one frozen piercing implement.
In one embodiment 18330, the at least one parameter for making the
at least one frozen piercing implement device includes one or more
of: constitution of the at least one frozen piercing implement of
the frozen piercing implement device, constitution of the at least
one frozen piercing implement device, formulation of the at least
one frozen piercing implement of the frozen piercing implement
device, formulation of the at least one frozen piercing implement
device, configuration of the at least one frozen piercing implement
of the device, configuration of the at least one frozen piercing
implement device, size of the at least one frozen piercing
implement of the frozen piercing implement device, size of the at
least one frozen piercing implement device, shape of the at least
one frozen piercing implement of the frozen piercing implement
device, shape of the at least one frozen piercing implement device,
physical structure of the at least one frozen piercing implement of
the frozen piercing implement device, physical structure of the at
least one frozen piercing implement device, physical or chemical
integrity of the at least one frozen piercing implement of the
frozen piercing implement device, or physical or chemical integrity
of the at least one frozen piercing implement device.
[1216] In one embodiment 18340, the at least one parameter for
administering at least one frozen piercing implement device to at
least one substrate includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
[1217] In one embodiment 18410, the at least one agent includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 18420, the at least one substrate includes
one or more of a cell, tissue, organ, structure, device, or food
product. In one embodiment 18430, the at least one frozen piercing
implement device includes one or more frozen piercing implements
that include at least one of hydrogen oxide, nitrogen, oxygen, air,
helium, neon, argon, xenon, chlorine, bromine, carbon dioxide,
acetone, ethyl acetate, dimethyl sulfoxide, dimethyl formamide,
dioxane, tetrahydrofuran, acetonitrile, acetic acid, n-butanol,
isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
[1218] In one embodiment 18440, the output includes one or more
instructions for making the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 18450, the output includes at
least one graphical description of the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 18460, the user includes at
least one entity. In on embodiment 18470, the entity includes at
least one person, or computer. In one embodiment 18480, the user
readable display includes a human readable display. In one
embodiment 18490, the user readable display includes one or more
active displays. In one embodiment 18495, the user readable display
includes one or more passive displays. In one embodiment 18510, the
user readable display includes one or more of a numeric format,
graphical format, or audio format. In one embodiment 18520, the
user readable display includes one or more of a display of one or
more differences in the comparison of at least one value related to
the first input and at least one value related to at least one
property of the at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device. In one
embodiment 18530, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition or frozen piercing
implement.
[1219] In one embodiment 18540, the at least one parameter for
making the at least one frozen particle composition or frozen
piercing implement includes one or more of: constitution of the at
least one frozen particle composition or frozen piercing implement,
formulation of the at least one frozen particle composition or
frozen piercing implement, size of the at least one frozen particle
composition or frozen piercing implement, density of the at least
one frozen particle composition or frozen piercing implement, shape
of the at least one frozen particle composition or frozen piercing
implement, physical structure of the at least one frozen particle
composition or frozen piercing implement, or physical or chemical
integrity of the at least one frozen particle composition or frozen
piercing implement. In one embodiment 18550, at least one parameter
for administering the at least one frozen particle composition or
frozen piercing implement includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
[1220] As illustrated in FIGS. 186-189, in one embodiment, a system
18600 comprises: 18610 at least one computing device; 18620 one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to receive a first
input associated with a first possible dataset, 18630 the first
possible dataset including data representative of at least one
parameter for making or administering at least one frozen particle
composition or frozen piercing implement; and 18640 one or more
instructions that when executed generate an output to a user
readable display.
[1221] In one embodiment 18650, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to compare a value
associated with the first possible dataset with a second dataset
including values of at least one predictive parameter for making
the at least one frozen particle composition or frozen piercing
implement.
[1222] In one embodiment 18660, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the second possible dataset.
[1223] In one embodiment 18670, the at least one parameter for
making the at least one frozen particle composition or frozen
piercing implement includes one or more of: constitution of the at
least one frozen particle composition or frozen piercing implement,
formulation of the at least one frozen particle composition or
frozen piercing implement, size of the at least one frozen particle
composition or frozen piercing implement, density of the at least
one frozen particle composition or frozen piercing implement, shape
of the at least one frozen particle composition or frozen piercing
implement, physical structure of the at least one frozen particle
composition or frozen piercing implement, or physical or chemical
integrity of the at least one frozen particle composition or frozen
piercing implement. In one embodiment 18710, at least one parameter
for administering the at least one frozen particle composition or
frozen piercing implement includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
[1224] In one embodiment 18720, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to determine from
the comparison at least one parameter for making or administering
at least one frozen particle composition or frozen piercing
implement to at least one substrate. In one embodiment 18730, the
system further comprises one or more instructions that when
executed on the at least one computing device cause the at least
one computing device to generate at least one response support
structured on the determination.
[1225] In one embodiment 18740, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to access the first
possible dataset in response to the first input. In one embodiment
18750, the system further comprises one or more instructions that
when executed on the at least one computing device cause the at
least one computing device to generate the first possible dataset
in response to the first input. In one embodiment 18760, the system
further comprises one or more instructions that when executed on
the at least one computing device cause the at least one computing
device to determine a graphical illustration of the first possible
dataset.
[1226] In one embodiment 18810, the at least one computing device
includes one or more of a desktop computer, workstation computer,
or computing system. In one embodiment 18820, the at least one
computing system includes one or more of a cluster of processors, a
networked computer, a tablet personal computer, a laptop computer,
a mobile device, a mobile telephone, or a personal digital
assistant computer. In one embodiment 18830, the output includes
one or more instructions for making the at least one frozen
particle composition or frozen piercing implement. In one
embodiment 18840, the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement.
[1227] In one embodiment 18850, the user includes at least one
entity. In one embodiment 18860, the entity includes at least one
person, or computer. In one embodiment 18870, the user readable
display includes a human readable display. In one embodiment 18880,
the user readable display includes one or more active displays. In
one embodiment 18890, the user readable display includes one or
more passive displays.
[1228] In one embodiment 18895, the user readable display includes
one or more of a numeric format, graphical format, or audio format.
In one embodiment 18898, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the first input and at least one
value related to at least one property of the at least one frozen
particle composition or frozen piercing implement.
[1229] In one embodiment 18910, the user readable display includes
one or more of a display of one or more differences in the
comparison of at least one value related to the second input and at
least one value related to at least one parameter for
administration of the at least one frozen particle composition or
frozen piercing implement.
[1230] As illustrated in FIGS. 190-192, one embodiment includes a
system 19000 comprising: 19010 circuitry for accepting a first
input associated with one or more parameters for making at least
one frozen particle composition or frozen piercing implement; 19020
circuitry for accepting a second input associated with one or more
parameters for administering at least one frozen particle
composition or frozen piercing implement to at least one substrate;
19030 circuitry for processing the first input and the second
input; and 19040 circuitry for generating an output to a user
readable display.
[1231] In one embodiment 19050, the one or more parameters for
making at least one frozen particle composition or frozen piercing
implement include at least one value derived from an image. In one
embodiment 19060, the image includes a 2-dimensional or
3-dimensional image. In one embodiment 19070, the image includes at
least one image acquired by one or more of x-ray crystallography,
laser, holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation.
[1232] In one embodiment 19080, the image includes at least one CAD
drawing. In one embodiment 19090, the image includes at least one
characteristic of the at least one frozen particle composition or
frozen piercing implement. In one embodiment 19095, the at least
one characteristic includes one or more of inner diameter, outer
diameter, shape, at least one major dimension, or constitution.
[1233] In one embodiment 19110, the system further comprises
circuitry for displaying results of the processing. In one
embodiment 19120, the system further comprises circuitry for
transmitting one or more signals that include information related
to the processing the first input and the second input. In one
embodiment 19130, the system further comprises circuitry for
evaluating the at least one substrate for one or more indicators
relating to one or more of: quantitative delivery of at least one
agent; depth of piercing the at least one substrate; spatial
coordinates for administration of at least one frozen particle
composition; at least one frozen piercing implement or at least one
agent; temporal coordinates for administration of at least one
frozen particle composition, at least one frozen piercing
implement, or at least one agent; substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; any substrate response to
administration of at least one frozen piercing implement, at least
one frozen particle composition, or at least one agent.
[1234] In one embodiment 19140, the at least one agent includes at
least one therapeutic agent, reinforcement agent, abrasive,
explosive material, adhesive agent, or biological remodeling agent.
In one embodiment 19150, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 19160,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing
implement.
[1235] In one embodiment 19170, the user includes at least one
entity. In one embodiment 19180, the entity includes at least one
person, or computer. In one embodiment 19210, the user readable
display includes a human readable display. In one embodiment 19220,
the user readable display includes one or more active displays. In
one embodiment 19230, the user readable display includes one or
more passive displays.
[1236] In one embodiment 19240, the user readable display includes
one or more of a numeric format, graphical format, or audio format.
In one embodiment 19250, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the first input and at least one
value related to at least one property of the at least one frozen
particle composition or frozen piercing implement. In one
embodiment 19260, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition or frozen piercing
implement.
[1237] As illustrated in FIGS. 193-195, in one embodiment a
computer program product 19300 comprises: 19310 a recordable medium
bearing one or more instructions for accepting a first input
associated with at least one parameter for making at least one
frozen particle composition or frozen piercing implement to at
least one substrate; 19320 one or more instructions for accepting a
second input associated with at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement; 19330 one or more instructions for
processing the first input and the second input; and 19340 one or
more instructions for generating an output to a user readable
display. In one embodiment 19350, the recordable medium includes a
computer-readable medium. In one embodiment 19360, the recordable
medium includes a communications medium.
[1238] In one embodiment 19370, the computer program product
further comprises one or more instructions for displaying results
of the processing. In one embodiment 19380, the computer program
product further comprises one or more instructions for transmitting
one or more signals that include information related to the
processing the first input and the second input. In one embodiment
19390, the computer program product further comprises one or more
instructions for evaluating the at least one substrate for one or
more indicators relating to one or more of: quantitative delivery
of at least one agent, depth of piercing the at least one
substrate, spatial location of delivery of at least one agent, or
temporal location of delivery of at least one agent. In one
embodiment 19395, the at least one agent includes at least one
therapeutic agent, reinforcement agent, abrasive, explosive
material, adhesive agent, or biological remodeling agent.
[1239] In one embodiment 19410, the first input includes at least
one parameter for making the at least one frozen particle
composition or frozen piercing implement includes one or more of:
constitution of the at least one frozen particle composition or
frozen piercing implement, formulation of the at least one frozen
particle composition or frozen piercing implement, configuration of
the at least one frozen particle composition or frozen piercing
implement, size of the at least one frozen particle composition or
frozen piercing implement, density of the at least one frozen
particle composition or frozen piercing implement, shape of the at
least one frozen particle composition or frozen piercing implement,
physical structure of the at least one frozen particle composition
or frozen piercing implement, or physical or chemical integrity of
the at least one frozen particle composition or frozen piercing
implement.
[1240] In one embodiment 19420, the second input includes at least
one parameter for administering the at least one frozen particle
composition or frozen piercing implement includes one or more of:
substrate type; substrate function; substrate size; substrate
constitution; substrate architecture; substrate durability;
substrate temperature; temperature of administration conditions;
depth of administration of the at least one frozen particle
composition or frozen piercing implement; substrate source; one or
more temporal coordinates; one or more spatial coordinates;
presence or absence of at least one agent; presence or absence of
at least one microparticle, nanoparticle, lens, tunablelens,
sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen piercing implement
device; force of administration of the at least one frozen piercing
implement device; velocity of administration of the at least one
frozen piercing implement device; quantity of frozen piercing
implements of the device; quantity of frozen piercing implement
devices administered; rate of administration of more than one
frozen piercing implement devices; method of administration of at
least one frozen piercing implement device; timing of
administration of at least one frozen piercing implement; or rate
of delivery of at least one agent of the device.
[1241] In one embodiment 19430, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 19440,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing
implement.
[1242] In one embodiment 19510, the user includes at least one
entity. In one embodiment 19520, the entity includes at least one
person, or computer. In one embodiment 19530, the user readable
display includes a human readable display. In one embodiment 19540,
the user readable display includes one or more active displays. In
one embodiment 19550, the user readable display includes one or
more passive displays. In one embodiment 19560, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 19570, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 19580, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
[1243] As illustrated in FIGS. 196-198, in one embodiment a system
19600 comprises: 19610 a recordable medium bearing one or more
instructions for accepting a first input associated with at least
one parameter for making at least one frozen particle composition
or frozen piercing implement; 19620 one or more instructions for
accepting a second input associated with at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement; 19630 one or more instructions for processing
the first input and the second input; and 19640 one or more
instructions for generating an output to a user readable
display.
[1244] In one embodiment 19650 the recordable medium includes a
computer-readable medium. In one embodiment 19660, the recordable
medium includes a communications medium. In one embodiment 19670,
the system further comprises one or more instructions for
transmitting one or more signals that include information related
to the processing the first input and the second input.
[1245] In one embodiment 19680, the system further comprises one or
more instructions for evaluating the at least one substrate for one
or more indicators relating to one or more of: quantitative
delivery of at least one agent, depth of piercing the at least one
substrate, spatial location of delivery of at least one agent, or
temporal location of delivery of at least one agent. In one
embodiment 19690, the at least one agent includes at least one
therapeutic agent, reinforcement agent, abrasive, explosive
material, adhesive agent, or biological remodeling agent.
[1246] In one embodiment 19710 the first input includes at least
one parameter for making the at least one frozen particle
composition or frozen piercing implement includes one or more of:
constitution of the at least one frozen particle composition or
frozen piercing implement, configuration of the at least one frozen
particle composition or frozen piercing implement, formulation of
the at least one frozen particle composition or frozen piercing
implement, size of the at least one frozen particle composition or
frozen piercing implement, density of the at least one frozen
particle composition or frozen piercing implement, shape of the at
least one frozen particle composition or frozen piercing implement,
physical structure of the at least one frozen particle composition
or frozen piercing implement, or physical or chemical integrity of
the at least one frozen particle composition or frozen piercing
implement.
[1247] In one embodiment 19720, the second input includes at least
one parameter for administering the at least one frozen particle
composition or frozen piercing implement includes one or more of:
substrate type; substrate function; substrate size; substrate
constitution; substrate architecture; substrate durability;
substrate temperature; temperature of administration conditions;
depth of administration of the at least one frozen particle
composition or frozen piercing implement; substrate source; one or
more temporal coordinates; one or more spatial coordinates;
presence or absence of at least one agent; presence or absence of
at least one microparticle, nanoparticle, lens, tunablelens,
sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen piercing implement
device; force of administration of the at least one frozen piercing
implement device velocity of administration of the at least one
frozen piercing implement device; quantity of frozen piercing
implements of the device; quantity of frozen piercing implement
devices administered; rate of administration of more than one
frozen piercing implement devices; method of administration of at
least one frozen piercing implement device; timing of
administration of at least one frozen piercing implement; or rate
of delivery of at least one agent of the device. In one embodiment
19730, the output includes one or more instructions for making the
at least one frozen particle composition or frozen piercing
implement.
[1248] In one embodiment 19810, the output includes at least one
graphical description of the at least one frozen particle
composition or frozen piercing implement. In one embodiment 19820,
the user includes at least one entity. In one embodiment 19830, the
entity includes at least one person, or computer. In one embodiment
19840, the user readable display includes a human readable display.
In one embodiment 19850, the user readable display includes one or
more active displays. In one embodiment 19860, the user readable
display includes one or more passive displays. In one embodiment
19870, the user readable display includes one or more of a numeric
format, graphical format, or audio format.
[1249] In one embodiment 19880, the user readable display includes
one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 19890, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
[1250] As illustrated in FIGS. 199-200, in one embodiment a system
19900 comprises: 19910 at least one computer program, configured
with a computer-readable medium, for use with at least one computer
system and wherein the computer program includes a plurality of
instructions including but not limited to: one or more instructions
for accepting a first input associated with one or more parameters
for making one or more frozen particle compositions or frozen
piercing implements to at least one substrate; one or more
instructions for accepting a second input associated with one or
more parameters for administering one or more frozen particle
compositions or frozen piercing implements; one or more
instructions for processing the first input and the second input;
and one or more instructions for generating an output to a user
readable display.
[1251] In one embodiment 19920, the system further comprises one or
more instructions for transmitting one or more signals that include
information related to the processing the first input and the
second input. In one embodiment 19930, the system further comprises
one or more instructions for evaluating the at least one biological
tissue for one or more indicators relating to one or more of:
quantitative delivery of at least one agent, depth of piercing the
at least one substrate, spatial location of delivery of at least
one agent, or temporal location of delivery of at least one
agent.
[1252] In one embodiment 19940, the at least one agent includes at
least one therapeutic agent, reinforcement agent, abrasive,
explosive material, adhesive agent, or biological remodeling agent.
In one embodiment 19950, the system further comprises at least one
computing device. In one embodiment 19960, the at least one
computing device is configured to communicate with at least one
printing device, at least one imaging device, or at least one input
device.
[1253] In one embodiment 19970, the first input includes at least
one parameter for making the at least one frozen piercing implement
device includes one or more of: constitution of the at least one
frozen piercing implement of the frozen piercing implement device,
constitution of the at least one frozen piercing implement device,
configuration of the at least one frozen piercing implement or
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, or physical or chemical integrity of the at least
one frozen piercing implement device.
[1254] In one embodiment 20010, the first input includes at least
one parameter for making the at least one frozen particle
composition or frozen piercing implement includes one or more of:
constitution of the at least one frozen particle composition or
frozen piercing implement, configuration of the at least one frozen
particle composition or frozen piercing implement, formulation of
the at least one frozen particle composition or frozen piercing
implement, size of the at least one frozen particle composition or
frozen piercing implement, density of the at least one frozen
particle composition or frozen piercing implement, shape of the at
least one frozen particle composition or frozen piercing implement,
physical structure of the at least one frozen particle composition
or frozen piercing implement, or physical or chemical integrity of
the at least one frozen particle composition or frozen piercing
implement.
[1255] In one embodiment 20020, the second input includes at least
one parameter for administering the at least one frozen particle
composition or frozen piercing implement includes one or more of:
substrate type; substrate function; substrate size; substrate
constitution; substrate architecture; substrate durability;
substrate temperature; temperature of administration conditions;
depth of administration of the at least one frozen particle
composition or frozen piercing implement; substrate source; one or
more temporal coordinates; one or more spatial coordinates;
presence or absence of at least one agent; presence or absence of
at least one microparticle, nanoparticle, lens, tunablelens,
sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen piercing implement
device; force of administration of the at least one frozen piercing
implement device; velocity of administration of the at least one
frozen piercing implement device; quantity of frozen piercing
implements of the device; quantity of frozen piercing implement
devices administered; rate of administration of more than one
frozen piercing implement devices; method of administration of at
least one frozen piercing implement device; timing of
administration of at least one frozen piercing implement; or rate
of delivery of at least one agent of the device.
[1256] In one embodiment 20030, the second input includes at least
one parameter for administering at least one frozen piercing
implement device to at least one substrate includes one or more of:
substrate type; substrate function; substrate size; substrate
constitution; substrate architecture; substrate durability;
substrate temperature; temperature of administration conditions;
depth of administration of the at least one frozen particle
composition or frozen piercing implement; substrate source; one or
more temporal coordinates; one or more spatial coordinates;
presence or absence of at least one agent; presence or absence of
at least one microparticle, nanoparticle, lens, tunablelens,
sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen piercing implement
device; force of administration of the at least one frozen piercing
implement device; velocity of administration of the at least one
frozen piercing implement device; quantity of frozen piercing
implements of the device; quantity of frozen piercing implement
devices administered; rate of administration of more than one
frozen piercing implement devices; method of administration of at
least one frozen piercing implement device; timing of
administration of at least one frozen piercing implement; or rate
of delivery of at least one agent of the device.
[1257] As illustrated in FIGS. 201-204, a system 20100, comprises:
20110 at least one computing device; 20120 one or more instructions
that when executed on the at least one computing device cause the
at least one computing device to receive a first input associated
with a first possible dataset, 20130 the first possible dataset
including data representative of at least one parameter for making
or administering at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device to at least
one substrate; and 20140 one or more instructions for generating an
output to a user readable display.
[1258] In one embodiment 20150, the at least one frozen piercing
implement device includes at least one frozen piercing implement
array device, frozen piercing implement fluidic device, or frozen
piercing implement injection device. In one embodiment 20160, the
frozen piercing implement injection device includes a frozen
piercing implement auto-injection device.
[1259] In one embodiment 20170, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to compare a value
associated with the first possible dataset with a second dataset
including values of at least one predictive parameter for
administering at least one frozen particle compositions or frozen
piercing implements to at least one substrate. In one embodiment
20180, the first input includes at least one parameter for making
the at least one frozen piercing implement device includes one or
more of: constitution of the at least one frozen piercing implement
of the frozen piercing implement device, constitution of the at
least one frozen piercing implement device, configuration of the at
least one frozen piercing implement or frozen piercing implement
device, formulation of the at least one frozen piercing implement
of the frozen piercing implement device, formulation of the at
least one frozen piercing implement device, size of the at least
one frozen piercing implement of the frozen piercing implement
device, size of the at least one frozen piercing implement device,
shape of the at least one frozen piercing implement of the frozen
piercing implement device, shape of the at least one frozen
piercing implement device, physical structure of the at least one
frozen piercing implement of the frozen piercing implement device,
physical structure of the at least one frozen piercing implement
device, physical or chemical integrity of the at least one frozen
piercing implement of the frozen piercing implement device, or
physical or chemical integrity of the at least one frozen piercing
implement device.
[1260] In one embodiment 20210, the second input includes at least
one parameter for administering at least one frozen piercing
implement device to at least one substrate includes one or more of:
substrate type; substrate function; substrate size; substrate
constitution; substrate architecture; substrate durability;
substrate temperature; temperature of administration conditions;
depth of administration of the at least one frozen particle
composition or frozen piercing implement; substrate source; one or
more temporal coordinates; one or more spatial coordinates;
presence or absence of at least one agent; presence or absence of
at least one microparticle, nanoparticle, lens, tunablelens,
sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen piercing implement
device; force of administration of the at least one frozen piercing
implement device; velocity of administration of the at least one
frozen piercing implement device; quantity of frozen piercing
implements of the device; quantity of frozen piercing implement
devices administered; rate of administration of more than one
frozen piercing implement devices; method of administration of at
least one frozen piercing implement device; timing of
administration of at least one frozen piercing implement; or rate
of delivery of at least one agent of the device.
[1261] In one embodiment 20220, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the second possible dataset. In one
embodiment 20230, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine from
the comparison at least one parameter for administering at least
one frozen particle composition, frozen piercing implement, or
frozen piercing implement device to at least one substrate.
[1262] In one embodiment 20240, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to generate at least
one response support structured on the determination.
[1263] In one embodiment 20250, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to access the first
possible dataset in response to the first input.
[1264] In one embodiment 20310, the system further comprises one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to generate the
first possible dataset in response to the first input. In one
embodiment 20320, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the first possible dataset. In one
embodiment 20330, the at least one computing device includes one or
more of a desktop computer, workstation computer, or computing
system.
[1265] In one embodiment 20340, the at least one computing system
includes one or more of a cluster of processors, a networked
computer, a tablet personal computer, a laptop computer, a mobile
device, a mobile telephone, or a personal digital assistant
computer. In one embodiment 20350, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 20360,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing
implement.
[1266] In one embodiment 20370, the user includes at least one
entity. In one embodiment 20380, the entity includes at least one
person, or computer. In one embodiment 20390, the user readable
display includes a human readable display. In one embodiment 20410,
the user readable display includes one or more active displays. In
one embodiment 20420, the user readable display includes one or
more passive displays. In one embodiment 20430, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 20440, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 20450, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
[1267] As illustrated in FIGS. 205-208, a system 20500 comprises:
20510 circuitry for accepting a first input associated with at
least one parameter for making at least one frozen piercing
implement device; 20520 circuitry for accepting a second input
associated with at least one parameter for administering at least
one frozen piercing implement device to at least one substrate;
20530 circuitry for processing the first input and the second
input; and 20540 circuitry for generating an output to a user
readable display. In one embodiment 20550, the at least one frozen
piercing implement device includes at least one frozen piercing
implement array device, frozen piercing implement fluidic device,
or frozen piercing implement injection device. In one embodiment
20560, the frozen piercing implement injection device includes a
frozen piercing implement auto-injection device. In one embodiment
20570, the first input includes at least one value derived from at
least one image. In one embodiment 20580, the at least one image
includes at least one 2-dimensional or 3-dimensional image. In one
embodiment 20590, the image includes at least one image acquired by
one or more of x-ray crystallography, laser, holography, optical
coherence tomography, computer-assisted tomography scan, computed
tomography, magnetic resonance imaging, positron-emission
tomography scan, ultrasound, x-ray, electrical-impedance
monitoring, microscopy, spectrometry, flow cytommetry, radioisotope
imaging, thermal imaging, infrared visualization, multiphoton
calcium-imaging, photography, or in silico generation.
[1268] In one embodiment 20610, the at least one image includes at
least one CAD drawing. In one embodiment 20620, the at least one
image includes at least one characteristic of the at least one
frozen piercing implement of the device or the frozen piercing
implement device. In one embodiment 20630, the at least one
characteristic of the one or more frozen piercing implement device
includes one or more of number of frozen piercing implements,
number of total piercing implements, size of at least one frozen
piercing implement, constitution of at least one frozen piercing
implement, shape of at least one frozen piercing implement, shape
of the device, configuration of the device, spacing of at least two
components of the device, spacing of at least two frozen piercing
implements of the device, or presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit.
[1269] In one embodiment 20640, the first input includes at least
one parameter for making the at least one frozen piercing implement
device includes one or more of: constitution of the at least one
frozen piercing implement of the frozen piercing implement device,
constitution of the at least one frozen piercing implement device,
configuration of the at least one frozen piercing implement or
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, physical or chemical integrity of the at least
one frozen piercing implement device, or presence or absence of at
least one microparticle, nanoparticle, lens, tunablelens, sensor,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, power source, injector, controller,
receiver, transmitter, or circuit, in the at least one frozen
piercing implement or frozen piercing implement device.
[1270] In one embodiment 20710, the second input includes at least
one parameter for administering the at least one frozen piercing
implement device includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
piercing implement device; force of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
[1271] In one embodiment 20720, the system further comprises
circuitry for transmitting one or more signals that include
information related to the processing the first input and the
second input. In one embodiment 20730, the system further comprises
circuitry for evaluating the at least one substrate for one or more
indicators relating to one or more of: quantitative delivery of at
least one agent, depth of piercing the at least one substrate,
spatial location of delivery of at least one agent, or temporal
location of delivery of at least one agent. In one embodiment
20740, the at least one agent includes at least one therapeutic
agent, reinforcement agent, abrasive, explosive material, adhesive
agent, or biological remodeling agent. In one embodiment 20750, the
output includes one or more instructions for making the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 20760, the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement.
[1272] In one embodiment 20810, the user includes at least one
entity. In one embodiment 20820, the entity includes at least one
person, or computer. In one embodiment 20830, the user readable
display includes a human readable display. In one embodiment 20840,
the user readable display includes one or more active displays. In
one embodiment 20850, the user readable display includes one or
more passive displays. In one embodiment 20860, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 20870, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 20880, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
[1273] As illustrated in FIGS. 209-211, a computer program product
20900 comprises: 20910 a recordable medium bearing one or more
instructions for accepting a first input associated with at least
one parameter for making at least one frozen piercing implement
device; 20920 one or more instructions for accepting a second input
associated with at least one parameter for administering the at
least one frozen piercing implement device to at least one
substrate; 20930 one or more instructions for processing the first
input and the second input; and 20940 one or more instructions for
generating an output to a user readable display.
[1274] In one embodiment 20950 the recordable medium includes a
computer-readable medium. In one embodiment 20960 the recordable
medium includes a communications medium. In one embodiment 20970
the computer program product further comprises one or more
instructions for displaying results of the processing. In one
embodiment 20980 the computer program product further comprises one
or more instructions for transmitting one or more signals that
include information related to the processing the first input and
the second input. In one embodiment 20990 the first input includes
at least one parameter for making the at least one frozen piercing
implement device includes one or more of: constitution of the at
least one frozen piercing implement of the frozen piercing
implement device, constitution of the at least one frozen piercing
implement device, configuration of the at least one frozen piercing
implement or frozen piercing implement device, formulation of the
at least one frozen piercing implement of the frozen piercing
implement device, formulation of the at least one frozen piercing
implement device, size of the at least one frozen piercing
implement of the frozen piercing implement device, size of the at
least one frozen piercing implement device, shape of the at least
one frozen piercing implement of the frozen piercing implement
device, shape of the at least one frozen piercing implement device,
physical structure of the at least one frozen piercing implement of
the frozen piercing implement device, physical structure of the at
least one frozen piercing implement device, physical or chemical
integrity of the at least one frozen piercing implement of the
frozen piercing implement device, physical or chemical integrity of
the at least one frozen piercing implement device, or presence or
absence of at least one microparticle, nanoparticle, lens,
tunablelens, sensor, transducer, actuator, detector, heater, valve,
gate, channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit, in the at least one
frozen piercing implement or frozen piercing implement device.
[1275] In one embodiment 21010, the at least one parameter for
administering at least one frozen piercing implement device to at
least one substrate includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
[1276] In one embodiment 21020, the computer program product
further comprises one or more instructions for evaluating the at
least one substrate for one or more indicators relating to one or
more of: quantitative delivery of at least one agent, depth of
piercing the at least one substrate, spatial location of delivery
of at least one agent, or temporal location of delivery of at least
one agent. In one embodiment 21030, the at least one agent includes
at least one therapeutic agent, reinforcement agent, abrasive,
explosive material, adhesive agent, or biological remodeling agent.
In one embodiment 21040, the at least one frozen piercing implement
device includes at least one frozen piercing implement array
device, frozen piercing implement fluidic device, or frozen
piercing implement injection device. In one embodiment 21050, the
frozen piercing implement injection device includes a frozen
piercing implement auto-injection device. In one embodiment 21060,
the output includes one or more instructions for making the at
least one frozen particle composition or frozen piercing
implement.
[1277] In one embodiment 21110, the output includes at least one
graphical description of the at least one frozen particle
composition or frozen piercing implement. In one embodiment 21120,
the user includes at least one entity. In one embodiment 21130, the
entity includes at least one person, or computer. In one embodiment
21140, the user readable display includes a human readable display.
In one embodiment 21150, the user readable display includes one or
more active displays. In one embodiment 21160, the user readable
display includes one or more passive displays. In one embodiment
21170, the user readable display includes one or more of a numeric
format, graphical format, or audio format. In one embodiment 21180,
the user readable display includes one or more of a display of one
or more differences in the comparison of at least one value related
to the first input and at least one value related to at least one
property of the at least one frozen particle composition or frozen
piercing implement. In one embodiment 21190, the user readable
display includes one or more of a display of one or more
differences in the comparison of at least one value related to the
second input and at least one value related to at least one
parameter for administration of the at least one frozen particle
composition or frozen piercing implement.
[1278] As illustrated in FIGS. 212-214, a system 21200 comprises:
21210 a recordable medium bearing one or more instructions for
accepting a first input associated with at least one parameter for
making at least one frozen piercing implement device; 21220 one or
more instructions for accepting a second input associated with at
least one parameter for administering at least one frozen piercing
implement device; 21230 one or more instructions for processing the
first input and the second input; and 21240 one or more
instructions for generating an output to a user readable display.
In one embodiment 21250, the at least one frozen piercing implement
device includes at least one frozen piercing implement array
device, frozen piercing implement fluidic device, or frozen
piercing implement injection device. In one embodiment 21260, the
frozen piercing implement injection device includes a frozen
piercing implement auto-injection device.
[1279] In one embodiment 21270, the recordable medium includes a
computer-readable medium. In one embodiment 21280, the recordable
medium includes a communications medium. In one embodiment 21290,
the system further comprises one or more instructions for
transmitting one or more signals that include information related
to the processing the first input and the second input. In one
embodiment 21310, the first input includes at least one parameter
for making the at least one frozen piercing implement device
includes one or more of: constitution of the at least one frozen
piercing implement of the frozen piercing implement device,
constitution of the at least one frozen piercing implement device,
configuration of the at least one frozen piercing implement or
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, physical or chemical integrity of the at least
one frozen piercing implement device, or presence or absence of at
least one microparticle, nanoparticle, lens, tunablelens, sensor,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, power source, injector, controller,
receiver, transmitter, or circuit, in the at least one frozen
piercing implement or frozen piercing implement device.
[1280] In one embodiment 21320, the second input includes at least
one parameter for administering the at least one frozen piercing
implement device includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
piercing implement device; force of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
[1281] In one embodiment 21410, the system further comprises one or
more instructions for evaluating the at least one substrate for one
or more indicators relating to one or more of: quantitative
delivery of at least one agent, depth of piercing the at least one
substrate, spatial location of delivery of at least one agent, or
temporal location of delivery of at least one agent. In one
embodiment 21420, the at least one agent includes at least one
therapeutic agent, reinforcement agent, abrasive, explosive
material, adhesive agent, or biological remodeling agent. In one
embodiment 21430, the output includes one or more instructions for
making the at least one frozen particle composition or frozen
piercing implement. In one embodiment 21440, the output includes at
least one graphical description of the at least one frozen particle
composition or frozen piercing implement.
[1282] In one embodiment 21450, the user includes at least one
entity. In one embodiment 21460, the entity includes at least one
person, or computer. In one embodiment 21470, the user readable
display includes a human readable display. In one embodiment 21480,
the user readable display includes one or more active displays. In
one embodiment 21485, the user readable display includes one or
more passive displays.
[1283] In one embodiment 21490, the user readable display includes
one or more of a numeric format, graphical format, or audio format.
In one embodiment 21495, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the first input and at least one
value related to at least one property of the at least one frozen
particle composition or frozen piercing implement. In one
embodiment 21498, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition or frozen piercing
implement.
[1284] As illustrated in FIGS. 215-218, a system 21500 comprises:
21510 at least one computer program, configured with a
computer-readable medium, for use with at least one computer system
and wherein the computer program includes a plurality of
instructions including but not limited to: one or more instructions
for accepting a first input associated with at least one parameter
for making at least one frozen piercing implement device; one or
more instructions for accepting a second input associated with at
least one parameter for administering at least one frozen piercing
implement device; one or more instructions for processing the first
input and the second input; and one or more instructions for
generating an output to a user readable display. In one embodiment
21520, the system further comprises one or more instructions for
transmitting one or more signals that include information related
to the processing the first input and the second input. In one
embodiment 21530, the system further comprises one or more
instructions for evaluating the at least one biological tissue for
one or more indicators relating to one or more of: quantitative
delivery of at least one agent, depth of piercing the at least one
substrate, spatial location of delivery of at least one agent, or
temporal location of delivery of at least one agent.
[1285] In one embodiment 21540, the at least one agent includes at
least one therapeutic agent, reinforcement agent, abrasive,
explosive material, adhesive agent, or biological remodeling agent.
In one embodiment 21650, the system further comprises at least one
computing device. In one embodiment 21660, the at least one
computing device is configured to communicate with at least one
printing device, at least one imaging device, or at least one input
device. In one embodiment 21670, the at least one frozen piercing
implement device includes at least one frozen piercing implement
array device, frozen piercing implement fluidic device, or frozen
piercing implement injection device. In one embodiment 21680, the
frozen piercing implement injection device includes a frozen
piercing implement auto-injection device.
[1286] In one embodiment 21710, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 21720,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 21730, the user includes at least one entity. In
one embodiment 21740, the entity includes at least one person, or
computer. In one embodiment 21750, the user readable display
includes a human readable display. In one embodiment 21760, the
user readable display includes one or more active displays. In one
embodiment 21770, the user readable display includes one or more
passive displays. In one embodiment 21780, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 21790, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 21795, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
[1287] In one embodiment 21810, the first input includes at least
one parameter for making the at least one frozen piercing implement
device includes one or more of: constitution of the at least one
frozen piercing implement of the frozen piercing implement device,
constitution of the at least one frozen piercing implement device,
configuration of the at least one frozen piercing implement or
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, physical or chemical integrity of the at least
one frozen piercing implement device, or presence or absence of at
least one microparticle, nanoparticle, lens, tunablelens, sensor,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, power source, injector, controller,
receiver, transmitter, or circuit, in the at least one frozen
piercing implement or frozen piercing implement device.
[1288] In one embodiment 21820, the second input includes at least
one parameter for administering the at least one frozen piercing
implement device includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
piercing implement device; force of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
[1289] The foregoing detailed description has set forth various
embodiments of the devices and/or processes via the use of block
diagrams, flowcharts, and/or examples. Insofar as such block
diagrams, flowcharts, and/or examples contain one or more functions
and/or operations, it will be understood by those within the art
that each function and/or operation within such block diagrams,
flowcharts, or examples can be implemented, individually and/or
collectively, by a wide range of hardware, software, firmware, or
virtually any combination thereof. In one embodiment, several
portions of the subject matter described herein can be implemented
via Application Specific Integrated Circuits (ASICs), Field
Programmable Gate Arrays (FPGAs), digital signal processors (DSPs),
or other integrated formats. However, those skilled in the art will
recognize that some aspects of the embodiments disclosed herein, in
whole or in part, can be equivalently implemented in integrated
circuits, as one or more computer programs running on one or more
computers (e.g., as one or more programs running on one or more
computer systems), as one or more programs running on one or more
processors (e.g., as one or more programs running on one or more
microprocessors), as firmware, or as virtually any combination
thereof, and that designing the circuitry and/or writing the code
for the software and or firmware would be well within the skill of
one of skill in the art in light of this disclosure. In addition,
those skilled in the art will appreciate that the mechanisms of the
subject matter described herein are capable of being distributed as
a program product in a variety of forms, and that an illustrative
embodiment of the subject matter described herein applies
regardless of the particular type of signal bearing medium used to
actually carry out the distribution. Examples of a signal bearing
medium include, but are not limited to, the following: a recordable
type medium such as a floppy disk, a hard disk drive, a Compact
Disc (CD), a Digital Video Disk (DVD), a digital tape, a computer
memory, etc.; and a transmission type medium such as a digital
and/or an analog communication medium (e.g., a fiber optic cable, a
waveguide, a wired communications link, a wireless communication
link (e.g., transmitter, receiver, transmission logic, reception
logic, etc.), etc.).
[1290] For any of the various aspects and embodiments disclosed
herein, one or more kits can be developed with the components
described herein. In one embodiment, a kit includes one or more
frozen particle compositions as described herein. In one
embodiment, a kit includes one or more frozen particle compositions
and at least one therapeutic agent as disclosed herein. In one
embodiment, a kit includes one or more frozen particle compositions
and one or more reinforcement agents. In one embodiment, a kit
includes one or more frozen particle compositions and one or more
explosive materials.
PROPHETIC EXAMPLES
Example 1
Compositions and Methods of Making Frozen Particles
[1291] Frozen particle compositions suitable for various
embodiments described herein can be produced by controlling the
pressure and temperature of hydrogen oxide that is introduced as a
liquid, gas or solid. Frozen particle compositions, including
frozen hydrogen oxide ice Ic, are produced by cooling small
hydrogen oxide droplets (.about.6 .mu.m diameter) below
approximately -38.degree. C. (See e.g., Murray, et al., Phys. Chem.
Chem. Phys. vol. 8, pp. 186-192 (2006), which is incorporated
herein by reference). Emulsions of 30-40% by weight of distilled
and de-ionized hydrogen oxide in paraffin oil (Fisher Scientific)
are agitated to produce hydrogen oxide droplets of mean diameters
ranging from 5 to 35 .mu.m as determined by optical microscopy. The
droplets are cooled to approximately -100.degree. C. at a rate of
approximately 10.degree. C./min by using a cryostat cooled with
liquid nitrogen and containing a heater and temperature controller.
Freezing liquid droplets with a median diameter of approximately
5.6 .mu.m or smaller can provide approximately 80% frozen ice Ic
and approximately 20% frozen ice 1h. Following the procedures of
Murray et al, selective production of ice Ic in pellet form
produces quantities suitable for use in various embodiments
described herein.
[1292] Frozen particles generated in this manner are utilized for
abrasion of at least one biological tissue, including but not
limited to skin. The frozen particle composition is administered to
at least one biological tissue by, for example, accelerating,
ejecting, or propelling the frozen particles by way of a carrier
gas under pressure (e.g., air, carbon dioxide, nitrogen, neon,
argon, etc.) through a tube, or other device directed toward at
least one biological tissue, such as skin. Microdermabrasion,
microscissuining, or other surface abrasion techniques are carried
out in a similar fashion.
Example 2
Compositions and Methods of Making Frozen Particles
[1293] Frozen particles, including frozen hydrogen oxide ice Ic,
are produced by depositing hydrogen oxide vapor onto a copper plate
held at low temperatures in vacuo. Purified (deionized) hydrogen
oxide is added to a vessel at approximately 25.degree. C. and the
hydrogen oxide vapor is condensed onto a metal plate held at
approximately -196.degree. C. in vacuo. The deposited amorphous ice
is heated (at 10.degree. C./min) to approximately -93.degree. C.
and is converted to crystalline cubic ice (ice Ic). Ice Ic is
stable when stored under liquid nitrogen (See e.g., Johari, et al.,
J. Phys. Chem., vol. 94, pp. 1212-1214 (1990), which is
incorporated herein by reference). An example of an apparatus that
is used to produce frozen hydrogen oxide ice Ic is described in
Hallbrucker et al (J. Phys. Chem., vol. 93, pp. 4986-4990 (1989),
which is incorporated herein by reference).
Example 3
Compositions and Methods of Making Frozen Particles
[1294] Frozen hydrogen oxide ice Ic particles are produced from
small hydrogen oxide droplets in an example of a "pelletizer"
apparatus similar to those described by, for example, U.S. Pat. No.
4,617,064; or U.S. Pat. No. 6,306,119, each of which is
incorporated herein by reference. Frozen hydrogen oxide ice Ic
particles are formed by spraying hydrogen oxide droplets of the
desired size into a compartment filled with a cold inert gas
maintained at the desired temperature, for example, nitrogen gas
maintained at approximately -100.degree. C. to promote formation of
ice Ic. Spray droplet size is maintained by variation of
nozzle/aperture size and hydrogen oxide pressure to yield droplet
diameters ranging from nanometers to centimeters. Frozen hydrogen
oxide ice Ic, ice Ih, amorphous low density ice, amorphous high
density ice, and other forms are produced by controlling the
temperature and pressure of the compartment. Cubic hydrogen oxide
ice Ic particles are formed in a step-wise process, by maintaining
the chamber at a very low temperature (approximately -196.degree.
C.) with increased pressure, which first promotes formation of
amorphous hydrogen oxide ice. Next, the chamber is heated to
approximately -93.degree. C., which results in transformation to
cubic hydrogen oxide ice (ice Ic) particles.
[1295] The hydrogen oxide ice particles are propelled into a
delivery system (such as tubing and nozzle) by nitrogen gas under
pressure. The delivery system is maintained at the appropriate
temperature for preservation of the hydrogen oxide particle
structure, (e.g., approximately -93.degree. C. for ice Ic
structure).
Example 4
Compositions and Methods of Making Frozen Carbon Dioxide
Particles
[1296] Carbon dioxide frozen particles are produced from small
carbon dioxide droplets in a "pelletizer" similar to those
described by, for example, U.S. Pat. No. 4,617,064; and U.S. Pat.
No. 6,306,119; each of which is incorporated herein by reference.
Carbon dioxide frozen particles are formed by spraying liquid
carbon dioxide droplets into a compartment maintained at low
temperatures (e.g., approximately -100.degree. C.). Droplet size is
regulated by varying nozzle or aperture size, and pressure. Carbon
dioxide droplet diameters range, for example, from nanometers to
centimeters. The frozen carbon dioxide particles are propelled into
a delivery system (e.g., tubing and nozzle) by carrier gas, (e.g.,
air or nitrogen) under pressure. The carbon dioxide particles are
maintained while in the delivery system at the appropriate
temperature, (e.g., approximately -100.degree. C.). Frozen carbon
dioxide particles sublimate, or transition to a gas phase, at
approximately -78.5.degree. C. and 1 atm pressure.
Example 5
Compositions and Methods of Making Frozen DMSO Particles
[1297] Dimethyl sulfoxide (DMSO) frozen particles are produced from
DMSO droplets. for example, in a "pelletizer" apparatus similar to
those described by, for example. U.S. Pat. No. 4,617,064; U.S. Pat.
No. 6,306,119, each of which is incorporated herein by reference.
DMSO frozen particles are formed from spraying liquid DMSO droplets
of the desired size into a compartment that is maintained at low
temperature, for example, less than approximately 18.5.degree. C.
Droplet size is regulated by varying nozzle or aperture size, and
DMSO pressure, with compressed air as a carrier gas. DMSO droplet
diameters range, for example, from nanometers to centimeters. The
DMSO frozen particles are propelled by a carrier gas (e.g., air or
nitrogen) under pressure to enter a delivery system (e.g., tubing
and nozzle). In order to preserve DMSO particle structure, the
delivery system is maintained at low temperature (e.g., less than
approximately 18.5.degree. C.).
Example 6
Methods of Assessment or Selection of Frozen Particles
[1298] According to various embodiments described herein, at least
one frozen particle is made by lowering the temperature of liquid
droplets of a selected material. Droplet and particle sizes are
measured by imaging a spray or particle stream upon a background
screen. The background screen is illuminated with a short pulse of
light, for example, from an infrared laser beam (at approximately
805 nm), which is capable of pulsing at frequencies of
approximately 1000 Hz.
[1299] A digital camera captures high resolution images of the
droplets or particles. High-speed, real-time particle sizing
software analyses the images to assess the diameter distribution
for the particles and to determine the shape. The diameter of each
droplet is determined automatically by referencing the number of
dark pixels in the droplet image to the pixel area of a calibration
circle. Droplet diameters between approximately 100 .mu.m
(.+-.3.2%) and approximately 2000 .mu.m (.+-.0.03%) were measured
with 95% confidence (See e.g., Ireland et al., 6th ASME-JSME
Thermal Engineering Joint Conference (2003), which is incorporated
herein by reference). Instruments, computer programs and protocols
for measuring particle and droplet size are available, for example,
from Oxford Lasers, Shirley, Mass. (e.g., world wide web at
oxfordlasers.com, which is incorporated herein by reference).
Example 7
Methods of Assessment or Selection of Frozen Particles
[1300] According to various embodiments described herein, at least
one frozen particle is made by lowering the temperature of liquid
droplets of a selected material. Droplet and particle sizes are
measured by laser diffraction. Laser diffraction based particle
size analysis relies on particles passing through a laser beam and
scattering light at an angle that is directly related to their
size. As particle size decreases, the observed scattering angle
increases logarithmically. Scattering intensity is also dependent
on particle size, and decreases with decreasing particle volume.
Thus, large particles scatter light at narrow angles with high
intensity whereas small particles scatter at wider angles but with
low intensity. Laser diffraction is used for the non-destructive
analysis of wet or dry samples, to measure particles in the size
range 0.02 to 2000 micrometers (e.g., world wide web at
chemie.de/articles/e/61205/, which is incorporated herein by
reference). A laser diffraction instrument, protocols and analysis
software are available, for example, from Malvern Instruments Ltd.
(Malvern, Worcestershire, WR14 1XZ United Kingdom).
Example 8
Compositions and Methods of Making Frozen Particles Including a
Reinforcement Agent
[1301] One or more reinforcement agents are added to the frozen
particles during the formation process. Among other things,
reinforcement agents can increase the strength of frozen particles
(e.g., increase the modulus of rupture of ice) and decrease the
deformation of frozen particles (e.g., decrease the beam deflection
of ice). As indicated in Table A below, glass fibers present at 9%
(wt./vol.), for example, increase the modulus of rupture of ice by
approximately 7-fold relative to ice derived from unreinforced
hydrogen oxide ice (See e.g., Kingery, Science, vol. 134, pp.
164-168 (1960), which is incorporated herein by reference).
TABLE-US-00005 TABLE A Strength of fresh ice with sawdust and
Fiberglass, respectively, added. Modulus of rupture (kg/cm.sup.2)
Addition (%) Sawdust (-17.degree. C.) Fiberglass (-20.degree. C.) 0
22.5 24.1 0.8 22.7 24.0 2.5 35 65.4 9.0 60 161 14.0 66.7 N/A
Additions were % wt./vol. (Kingery, Ibid).
[1302] As indicated in FIG. 5, the beam deflection is less than
0.005 inches for hydrogen oxide ice that is reinforced with
approximately 9.0% glass fibers and increases over time for
hydrogen oxide ice that is reinforced with approximately 0.8% glass
fibers (Kingery, Ibid). Furthermore, hydrogen oxide ice with
approximately 9% (w/v) of glass fibers is not deformed over 23
hours under an applied force of approximately 24.5 in.lbs. As
described in Kingery, et al, and as indicated in FIG. 5, beam
deflection of hydrogen oxide ice with approximately 0.8% glass
fibers is approximately 0.16 inches after 23 hours under 25.3
inlbs. of force. Likewise, as indicated in FIG. 5, and according to
Kingery et al, hydrogen oxide ice without reinforcement agents is
deformed approximately 0.05 inches after 4 hours under
approximately 26.6 inlbs. of force. Additionally, aluminum and
silica carbonate particles can be mixed at various volume fractions
and co-milled under an argon atmosphere to produce nanocrystalline
composites as reinforcement agents for frozen particle
compositions. (See e.g., Kamrani, et al., Powder Met. vol. 50, pp.
276-282(7) (2007), which is incorporated herein by reference).
Example 9
Compositions and Methods of Making Frozen Particles
[1303] Frozen particles (e.g., carbon dioxide, DMSO, gelatin) are
reinforced by incorporating one or more reinforcement agents,
including but not limited to silica beads, fiberglass, polyethylene
glycol, kaolin, or wood fibers.
[1304] Silica beads approximately 1 micrometer in diameter are
mixed with hydrogen oxide at approximately 0.degree. C. to make
volume fractions including the approximate ranges, but not limited
to, 0, 0.004, 0.04, 0.15, 0.29, 0.49 and 0.63 volume fraction. The
volume fractions, or one or more particular volume fraction, are
frozen in, for example, a cylindrical mold, at low temperatures
(e.g., approximately -10.degree. C.). Unconfined coaxial
compression tests are used to determine the maximum stress (also
known as the failure point) of the one or more frozen particles at
defined temperatures and strain rates (See e.g., Yasui et al,
Geophys. Res. Lett., vol. 35, L12206, (2008), which is incorporated
herein by reference).
[1305] As indicated in FIG. 6, maximum stress. values (MPa)
increase for mixtures with an increased volume fraction of silica
beads relative to the maximum stress for unreinforced hydrogen
oxide ice. (See e.g., Yasui et al, Ibid.) .phi.=silica volume
fraction
[1306] The strength of specific frozen particles is altered by
varying the composition of frozen particle mixtures containing one
or more reinforcement agents. For example, Table B indicates the
frozen particle strength of frozen particles including hydrogen
oxide, DMSO, carbon dioxide, and gelatin, which contain at least
one reinforcement agent. As indicated, the reinforced frozen
particles exhibited increased strength compared to their
unreinforced counterparts. As indicated in Table B, frozen
particles containing at least one reinforcement agent at the volume
fractions shown in the table displayed maximal strength in
compression tests. (See also, FIGS. 5 and 6, as well as Table A
herein for hydrogen oxide frozen particle strength).
TABLE-US-00006 TABLE B Frozen particles and reinforcement agents
leading to increased particle strength Particle Base Fiber Glass
Saw Dust Silica Beads PEG Kaolin Ice 0.15* 0.14 0.63 ND 0.15 DMSO
0.15 0.14 0.63 ND 0.15 carbon 0.15 0.14 0.63 ND 0.15 dioxide
Gelatin 0.15 0.14 0.63 ND 0.15 Volume fraction for reinforcement
agents in frozen particle base materials is given. ND = Not
Determined. (Yasui, et al.)
Example 10
Vaccine Compositions and Methods of Making Frozen Particles
[1307] As described herein, immunization of a subject with a
vaccine is accomplished by way of introduction of the vaccine
through, for example, subcutaneous, transcutaneous or intramuscular
administration. (See e.g., Berzofsky et al, Nat. Rev. Immunol. vol.
1, pp. 209-219, (2001), which is incorporated herein by reference).
Non-limiting examples of frozen particle vaccines are described
herein, and include one or more immunogens. The immunogen
therapeutic compositions are made, for example, in solution or as a
solid in suspension or as a colloid created from, for example,
buffered solutions (e.g., phosphate, citrate, lactate, pyruvate or
an organic acid buffer) that optimize the stability and
immunogenicity of the vaccine.
[1308] Storage stability of vaccines depends upon many factors,
including vaccine formulation and storage temperature. For example,
an influenza subunit vaccine formulated with trehalose, and Hepes
buffered saline, is stable at room temperature for approximately 26
weeks (See e.g., Amorij et al, Pharm. Res. vol. 25, pp. 1256-1273
(2008), which is incorporated herein by reference).
[1309] Vaccines with adjuvants such as: N-acetyl
muramyl-1-alanyl-d-isoglutamine, also called muramyl dipeptide
(MDP) or monophosphoryl lipid A (MPL) elicit enhanced cellular and
humoral immunity (See e.g., Aguilar et al Vaccine vol. 25, pp.
3752-62 (2007), which is incorporated herein by reference).
[1310] Furthermore, stable genetic transformation and vaccination
of intact plant cells has been achievable by particle bombardment
processes (See e.g., Klein et al PNAS vol. 85, pp. 8502-8505
(1988), and Klein et al BioTech vol. 24, pp. 384-386 (1992); each
of which is incorporated herein by reference).
[1311] One or more hydrogen oxide frozen particle vaccine
compositions, including, for example, one or more buffers, one or
more immunogens (e.g., viral protein subunits) and one or more
adjuvants, as a solution or suspension, are made by spraying the
compositions through an aperture or nozzle. Each vaccine
composition is propelled by a pressurized gas (e.g., compressed
air) into a compartment maintained at, for example, approximately
-40.degree. C.
[1312] The vaccine composition is delivered to at least one
biological tissue of a subject, for example, by propelling the
particles via a carrier gas under pressure (e.g., air, carbon
dioxide, nitrogen) through a tube directed toward at least one
biological tissue (including but not limited to plant callus, plant
leaves, plant roots, plant stems, vasculature, lymphatic, lymph
node, epidermis, subcutaneous, intramuscular, oral, nasal,
pulmonary, intraperitoneal or rectal tissue).
[1313] Alternatively, the vaccine composition is delivered to at
least one biological tissue of a subject, for example, by first
forming the frozen particle vaccine compositions through spraying
composition droplets into a cryogen bath (e.g., liquid nitrogen).
The frozen particle compositions are subsequently delivered to at
least one biological tissue by flash boiling liquid nitrogen, and
propelling the frozen particle compositions through a tube or
barrel, for example, to at least one biological tissue of a
subject.
[1314] Frozen particle vaccine compositions containing one or more
reinforcement agents (e.g., silica beads) and of the appropriate
size and shape (e.g., bullet, spheroid, high aspect ratio shape)
penetrate the at least one biological tissue when propelled to high
velocity by a carrier gas. In one non-limiting example, a vaccine
composition approximately 20-70 .mu.m in size penetrates the
epidermis when the composition is accelerated to high speed with a
powder jet injector (PowerJect, PowerJect Pharmaceuticals) (Amorij
et al, Ibid.).
[1315] Similarly, one group found that using the Bio-Rad HELIOS
Gene Gun.RTM. and microparticle-delivery of pCMV-S DNA vaccination
in mice resulted in greater numbers of animals achieving immunity
than those receiving intramuscular injection. (See, e.g., Conn et
al, Bio-Rad Tech Note 2726, available on the worldwide web at
bio-rad.com/LifeScience/pdf/Bulletin.sub.--2726.pdf, accessed Feb.
12, 2009, the content of which is incorporated herein by
reference.)
[1316] For plant leaves, a high rate of infection with a
Potyviridae virus was obtained by another group using the Bio-Rad
HELIOS Gene Gun.RTM. and microparticle-delivery of the virus. (See,
e.g., Kekarainen and Valkonen, Bio-Rad Tech Note 2531, available on
the worldwide web at
bio-rad.com/LifeScience/pdf/Bulletin.sub.--2531.pdf, accessed Feb.
12, 2009, the content of which is incorporated herein by
reference.) The authors found optimal infection rates in plant
leaves under a helium pressure of 150 psi or 200 psi, at a distance
of 0 cm from the delivery device to the tissue. (Id. at page
2).
Example 11
Vaccine Compositions and Methods of Making Frozen Particles
[1317] Frozen particle vaccine compositions containing multiple
immunogens, for example, toxoids (chemically modified toxins) from
bacteria such as Clostridium tetani, Cornybacterium diphtheriae or
Bordetella pertussis, stimulate immunity to multiple bacteria or
toxins in a single vaccine composition.
[1318] Alternatively, multiple distinct immunogens, proteins, or
peptides that are derived from a single pathogen are combined in a
single frozen particle vaccine composition that immunizes a subject
against a pathogenic virus or bacteria that mutates frequently. For
example, multiple hemagglutinin or neuraminidase proteins, (e.g.,
H1N1, H3N2) from different viral strains (e.g., A/New
Calcdonia/H1N1, or A/Wellington/H3N2) or viral species of influenza
(e.g., influenza A or influenza B) are combined in a single frozen
particle vaccine composition and provides immunity to multiple
strains or species. (See e.g., Kamps et al, Influenza Report, pp.
127-149 (2006); world wide web at influenzareport.com/ir/vaccines;
each of which is incorporated herein by reference).
[1319] Alternatively, frozen particle vaccine compositions
including one or more immunogens, antigens or proteins (e.g.,
influenza A/New Calcdonia/(H1N1)) are combined with one or more
frozen particle vaccine compositions containing one or more
different antigens (e.g., influenza B/Shanghai or influenza
A/Wellington/(H3N2)). Such a frozen particle vaccine composition
combination provides immunity against seasonal variants of viral
pathogens.
[1320] In one non-limiting example, combinations of frozen particle
vaccine compositions including specific antigens from selected
influenza variants or strains target a seasonal flu epidemic.
(Kamps et al, Ibid.) Combination of frozen particle compositions
are made containing one or more different antigens or epitopes,
wherein the one or more different antigens or epitopes are derived
from mutant or variant HW proteins that evolve during HIV infection
(See e.g., Berzofsky et al, J. Clin. Inv. vol. 114, pp. 450-462
(2004)). Such combination compositions immunize a subject against
existing HIV mutants and anticipate the emergence of new HIV
mutants or variants.
[1321] Alternatively, one or more frozen particle vaccine
compositions are delivered to one or more mucosal tissues (e.g.,
nasal, oral, rectal, pulmonary) via propulsion using a "pellet
gun," via inhalation, or ingestion by a subject. For example, an
influenza vaccine lyophilized and delivered nasally as spherical
particles, approximately 26.9 .mu.m (mean diameter), induces
mucosal (e.g., nasal IgA response) and systemic immunity (e.g.,
serum antibody response) to influenza virus (See e.g., Garmise et
al, AAPS PharmSciTech. vol. 8:E81 (2007); Huang et al, Vaccine.
vol. 23(6), pp. 794-801 (2004); each of which is incorporated
herein by reference).
[1322] Alternatively, the one or more frozen particle vaccine
compositions are delivered to one or more pulmonary surfaces of the
subject via propulsion by way of a "pellet gun," by using flash
boiled liquid nitrogen as a propellant, or by inhalation. Frozen
particle influenza vaccine compositions administered to one or more
pulmonary surfaces of a subject elicit mucosal and systemic
humoral, as well as cell-mediated immune responses to influenza
(See e.g., Amorij et al Vaccine. vol. 25, pp. 8707-8717 (2007),
which is incorporated herein by reference).
Example 12
Compositions and Methods of Making Frozen Particles
[1323] Frozen particle compositions of the appropriate size and
shape, including botulinum toxin, an optimal buffer (e.g., Hepes
buffer), one or more stabilizing agents, and one or more
reinforcement agents are administered through the skin of a subject
to neuromuscular junctions. Botulinum toxin inhibits acetylcholine
release, which blocks synapse formation, and temporarily paralyzes
the corresponding musculature.
[1324] Frozen particle compositions containing a recommended dose
of botulinum toxin (See e.g., Borodic, U.S. Pat. No. 5,183,462,
which is incorporated herein by reference), and at least one
reinforcement agent (e.g., polymer) are administered to skeletal
muscles using a delivery system derived from inkjet printer
technology that sprays picoliter quantities of the frozen particle
compositions at high velocity (e.g., 50 msec) toward the skin of
the subject. Botulinum toxin is typically administered by
subcutaneous injection (generally with a 26 gauge hypodermic
needle). Botulinum toxin is approved by the FDA for therapy of
strabismus (crossed-eyes), blepharospasm (uncontrolled blinking),
and other facial nerve disorders including hemifacial spasm. It is
also approved for treatment of cervical dystonia and glabellar
(frown) lines (See e.g., Jankovic, J. Neurol. Neurosurg. Psychiatry
vol. 75, pp. 951-957 (2004), which is incorporated herein by
reference).
[1325] In addition, botulinum toxin is included in the treatment of
focal or segmental dystonia (e.g., oromandibular-facial-lingual
dystonia, laryngeal dystonia, limb dystonia). Dystonias are
neurological disorders with repetitive and patterned contractions
of muscles that cause abnormal movements and postures. For example,
cervical dystonia subjects are injected with, for example,
approximately 100 I.U of botulinum toxin, distributed over 3-5
injection sites, spaced 5-15 mm apart, across the length of the
sternomastoid muscle. (Borodic, Ibid.)
[1326] Frozen particle compositions containing botulinum toxin are
administered to facial muscles that underlie frown lines, wrinkles,
and "crow's feet." For example, botulinum toxin is targeted to: 1)
the corrugator and procerus muscles to treat vertical glabellar
eyebrow furrows; 2) to multiple sites in the frontalis muscle to
eliminate horizontal lines in the forehead; or 3) to the lateral
orbicularis oculi to treat crow's feet.
[1327] Frozen particle compositions containing an optimal dose of
botulinum toxin (e.g., 0.2-0.4 I.U./kg) are administered over the
length of a specific facial muscle (e.g., orbicularis oculi) by use
of a delivery system with an inkjet nozzle. As described herein,
picoliter volumes of one or more frozen particle compositions are
sprayed at a velocity that achieves a desired or predetermined
depth (for example, 5-8 mm; Borodic, Ibid.). The velocity is also
altered according to the size, shape, and constituents of the
frozen particle composition.
Example 13
Methods of Administering Frozen Particle Therapeutic
Compositions
[1328] Frozen hydrogen oxide particles of ice Ic form and at least
one therapeutic agent or at least one diagnostic agent are
formulated for treatment of hematological cancers (e.g., leukemia
or lymphoma) or solid tumors (e.g., carcinoma, sarcoma). For
example, at least one of neo-adjuvant therapy, adjuvant therapy,
chemotherapy, antibody therapy, or immunotherapy are employed.
[1329] In one non-limiting embodiment, frozen particle compositions
are used for adjuvant therapy of cancers treated with surgery such
as colon cancer, lung cancer, and breast cancer. At least one
frozen particle hydrogen oxide therapeutic composition containing
one or more reinforcement agents (e.g., silica beads, Kevlar.RTM.),
one or more buffers, one or more stabilizing agents (e.g., one or
more saccharides), and one or more cancer therapeutic agents (such
as one or more chemotherapy drugs, antibodies, biological agents
(e.g., antibodies, cytokines or peptides), or one or more
chemotherapeutic agents) are administered to an area proximal to a
region of at least one biological tissue where a tumor is present
or believed to be present. Optionally, resection of at least a part
of a tumor can be performed, with or without additional
administration of the at least one frozen particle therapeutic
composition.
[1330] The at least one frozen particle therapeutic composition is
administered in such a manner as described herein, that allows for
desired depth of penetration of the at least one biological tissue.
In one embodiment, the at least one frozen particle therapeutic
composition is administered to a depth that allows for at least one
of intracellular or intercellular delivery. For example, the at
least one frozen particle therapeutic composition is administered
to a depth that allows for delivery to at least one of epithelium,
endothelium, vasculature, lymphatic vessels, lymph nodes or
mucosa.
[1331] Specifically, if metastasis is present or believed to be
present in the subject, administration of the at least one frozen
particle therapeutic composition is delivered to such region of
metastases or micro-metastases are believed to be present.
[1332] Frozen particle hydrogen oxide therapeutic compositions
provided as an adjuvant therapy are administered by spraying at
least one composition under pressure with a carrier gas through a
nozzle designed to uniformly distribute particles over at least one
biological tissue at sufficient velocity to penetrate the tissue
exposed during tumor resection.
[1333] Advanced colon cancer (e.g., stage II, III) is treated
surgically by removal of sections of colon containing tumor with
margins of "normal" colon tissue and often includes removal of
associated lymph nodes and mesentery (colectomy). Standard adjuvant
therapy following surgery is systemic administration of a
combination of chemotherapy drugs (e.g., 5-fluorouracil, leucovorin
or oxaliplatin (FOLFOX)), (See e.g., Wolpin et al, CA Cancer J.
Clin. vol. 57, pp. 168-185 (2007)). Systemic FOLFOX adjuvant
therapy is associated with significant toxicities including
gastrointestinal toxicity, neutropenia and neurotoxicity (Wolpin et
al, Ibid.). Localized in situ delivery of FOLFOX by administration
of frozen particle therapeutic compositions permits delivery of a
lower dose.
[1334] Administration of at least one frozen particle hydrogen
oxide therapeutic composition containing at least one therapeutic
antibody includes, for example, bevacizumab (an anti-vascular
endothelial growth factor) or cetuximab (an anti-epidermal growth
factor receptor). Bevacizumab and cetuximab both target the
tumor-associated vasculature and tumor cells in the remaining colon
sections and the surrounding tissues, mesentery and lymph nodes.
Localized administration of therapeutic antibodies provides
sustained protection from recurrence of colon tumors at the site of
tumor resection and in the surrounding tissues. (Wolpin et al,
Ibid.). Following surgery and adjuvant therapy with one or more
frozen particle hydrogen oxide therapeutic compositions, including
at least one of one or more chemotherapy drugs, or one or more
antibodies, the remaining colon sections are spliced together (i.e.
anastomosis) or an artificial orifice (i.e. stoma) is inserted to
restore a functional colon.
Example 14
Methods of Administering Frozen Particle Therapeutic
Compositions
[1335] Frozen particle hydrogen oxide therapeutic compositions
including one or more cancer therapeutics or one or more cancer
diagnostics are used to treat cancers in distal locations from the
primary tumor or initial tumor site treated with surgery or
radiation. For example, colon cancer cells often metastasize to the
liver ((Wolpin et al, Ibid.). At the time of surgical resection of
colon cancer tumors, one or more frozen particle hydrogen oxide
therapeutic compositions including at least one cancer therapeutic,
such as one or more cytotoxic drugs (e.g., fluouracil), antibodies
(e.g., cetuximab), radioisotopes conjugated to antibodies (e.g.,
.sup.131I-cetuximab), or one or more mixtures of at least one
cytotoxic drug and at least one biological-based therapeutic agent
are administered to the liver and surrounding tissues.
[1336] Administration of the at least one frozen particle hydrogen
oxide therapeutic composition is accomplished by traditional
surgery or laparoscopic surgery that allows access to the liver (or
other organs to be treated). Administration of at least one frozen
particle hydrogen oxide therapeutic composition directly to the
liver and the surrounding vasculature allows for intracellular or
intercellular penetration and release of at least one anti-cancer
therapeutic for treatment of any existing or suspected colon cancer
mestastases or micro-metastases.
[1337] As described herein, the at least one frozen particle
hydrogen oxide therapeutic composition including one or more cancer
therapeutics are administered by way of a spraying device. Such a
spraying device includes an insulated tube and nozzle, as well as a
valve that controls the flow of particles. In the case of
traditional surgery for tumor or tissue resection, the at least one
frozen particle hydrogen oxide therapeutic composition is sprayed
directly onto the target tissue or tissues. Whereas in the case of
laparoscopic surgery for tumor or tissue resection, the at least
one frozen particle hydrogen oxide therapeutic composition is
sprayed through a trocar (a hollow tube approximately 10
millimeters in diameter).
[1338] In certain spraying devices, the at least one frozen
particle hydrogen oxide therapeutic composition is administered by
way of a carrier gas. The depth of penetration by the at least one
therapeutic composition is controlled by regulating the carrier gas
pressure as well as the consequent particle velocity. The at least
one therapeutic composition optionally includes one or more tracer
agents or is delivered simultaneously with one or more tracer
agents. Some non-limiting examples of tracer agents include dyes,
stains or fluorescent compounds that mark the tissue area sprayed.
The one or more tracer agents can optionally monitor or provide
feedback as to the quantity or quality (in the case of multiple
therapeutic compositions administered simultaneously or over time)
of the at least one therapeutic composition administered to a
specific site.
[1339] In one embodiment, the at least one frozen particle hydrogen
oxide therapeutic composition including at least one cancer
therapeutic further includes hematoxylin and eosin stains mixed at
a known ratio (e.g., 1:10). Alternatively, a batch of the at least
one frozen particle hydrogen oxide therapeutic composition is
administered in a mixture or in separate applications frozen
particles including hematoxylin and eosin stains. Staining of
tissues is visualized by inspection with a low power microscope
(e.g., dissection microscope) or with a laparoscope, which allows
for assessment of the relative quantity or quality of the at least
one therapeutic composition administered to the tissue. Staining of
the tissues further provides a guide as to the region that received
the at least one therapeutic composition.
Example 15
Methods of Administering Frozen Particle Therapeutic
Compositions
[1340] Frozen particle hydrogen oxide therapeutic compositions
including carbon dioxide and at least one cancer therapeutic are
administered to at least one tumor or tissue suspected of being
cancerous. Upon administration, the frozen particle hydrogen oxide
therapeutic compositions penetrate one or more tumor cells, warm to
ambient temperature, and undergo rapid sublimation and gaseous
expansion of the carbon dioxide. This rapid reaction produces a
small explosion that destroys at least one tumor cell as well as
one or more adjacent cells. In addition, administration of the
frozen particle therapeutic compositions at low temperatures (e.g.,
lower than approximately -78.5.degree. C., which is the approximate
sublimation temperature for carbon dioxide at 1 atm pressure),
freezes cells and tissues, causing tumor cell death (See e.g.,
Vergnon et al, Eur. Respir. J. vol. 28 pp. 200-218 (2006);
incorporated herein by reference).
[1341] Alternatively, carbon dioxide gas is entrapped in frozen
particles by placing the liquid phase (e.g., hydrogen oxide) under
high pressure in the presence of carbon dioxide gas. (See e.g.,
U.S. Pat. Nos. 4,289,794; 4,289,790; 4,262,029; 5,439,698, each of
which is incorporated herein by reference). Administration of the
at least one therapeutic composition is conducted as described
herein. In one embodiment, the use of a tube and nozzle is used
that sprays the frozen particle therapeutic compositions under
pressure in a carrier gas (e.g., carbon dioxide, nitrogen).
Administration of the at least one therapeutic composition is
carried out as an adjuvant therapy in conjunction with tumor
resection, or as an alternative when tumor resection is not
favored. For example lung cancer tumors are generally inoperable
when such tumors are adjacent to airways, or infiltrate central
airways including the trachea, main stem bronchi or multiple lung
lobes. Additionally, subjects with compromised respiration (e.g.,
those with lung disease, heart disease or advanced age) are
generally not candidates for surgery (See e.g., Spiro et al, Amer.
J. Respir. Crit. Care Med., vol. 172, pp. 523-529 (2005); which is
incorporated herein by reference).
[1342] Carbon dioxide frozen particle therapeutic compositions
including one or more chemotherapeutic drugs (e.g., cisplatin,
docetaxel, vinorelbine), targeted drugs (e.g., gefitnib, erlotnib),
or biological-based agents (e.g., cetuximab, panitumumab,
bevacizumab) are administered directly onto lung cancer tumors.
Administration is conducted via endoluminal bronchoscopy or by
video-assisted thoracoscopy by means of an insulated tube and
nozzle integral to the endoscopic device. Frozen particle
composition velocities and spray rate are controlled by a valve
between the spray head and the compartment of the "pelletizer."
(See e.g., U.S. Pat. No. 6,306,119, or 6,764,493, each of which is
incorporated herein by reference). Precise localization and
administration of the frozen particle therapeutic compositions are
accomplished by bronchoscopy and endoscopy with fluoroscopy used to
mark the field(s) of interest.
[1343] Methods for endoscopic targeting of tumors are described,
for example, in Huber et al (Chest vol. 107, pp. 463-470 (1995);
which is incorporated herein by reference). Moreover, computed
tomography, magnetic resonance imaging, positron emission
tomography or other techniques are used to locate lung cancer
tumors.
[1344] Frozen particle therapeutic composition administration by
using endoscopic procedures or as an adjuvant therapy in
conjunction with traditional surgery is used for various regions of
existing or potential carcinogenesis, including mediastinal lymph
nodes, vasculature, chest wall and other thoracic sites.
[1345] Alternatively, frozen particle therapeutic compositions are
delivered during traditional surgery for lung cancer and used to
treat inoperable tumors remaining following lobectomy, wedge
resection, and pneumonectomy, as well as to treat margins of lobe,
wedge or lung excisions to reduce recurrence of lung cancer (See
e.g., the worldwideweb at
en.wikipedia.org/wiki/Lung_cancer#Surgery; which is incorporated
herein by reference). Without wishing to be bound by any particular
theory, frozen particle carbon dioxide therapeutic compositions
maintained at approximately -80.degree. C. while administered to
tumors rapidly freeze the tumor cells leading to formation of ice
crystals in tumor cells that destroy cell organelles (e.g.,
mitochondria) leading to death of the tumor cells. (Vergnon et al,
Ibid.)
[1346] Similarly, frozen particle therapeutic compositions
containing at least one radioactive element deliver radiation to
lung cancer tumor cells. One non-limiting example utilizes frozen
particle therapeutic compositions including .sup.192Iridium for
irradiating lung tumors that obstruct major airways. Administration
of the frozen particle therapeutic compositions is conducted using
an endoscope and a wire to place the radioactive compositions in at
least one lung tumor. Without wishing to be bound to any theory,
tumor cell irradiation results in single-stranded DNA breaks that
induce apoptosis and reduce rates of cell division (Vergnon et,
Ibid.).
Example 16
Compartmentalized Frozen Particle Therapeutic Compositions
[1347] Frozen particles formed in a bullet-shaped mold with hollow
cores or cavities that can be filled with therapeutics are useful
for delivering at least one therapeutic agent to a variety of
specific tissues, cells and organ or body locations. Hollow
bullet-shaped frozen particles can be filled with a therapeutic
agent such as one or more of an antibody, cytokine, DNA, small
interfering RNA, microRNA, aptamer, cytotoxic agent (e.g. a
xenobiotic, synthetic, or radioactive agent) that are in aqueous
solution (e.g. sodium phosphate buffer) or form a suspension.
Alternatively, hollow frozen bullets can be filled with one or more
liquid or solid polymers or nanoparticles that contain at least one
therapeutic agent (e.g. at least one prodrug) that requires
activation.
[1348] In one particular embodiment, at least one therapeutic agent
is frozen in carbon dioxide. The frozen carbon dioxide/therapeutic
agent mixture or solution is used to fill pre-formed hollow
bullet-shaped frozen particles. In certain embodiments, the hollow
bullet-shaped frozen particles are formed and filled
simultaneously. The temperature and pressure of the frozen
particles are adjusted according to the particular constituents and
specific parameters of the desired frozen particle.
[1349] Administration of at least one compartmentalized therapeutic
frozen particle composition with a spraying device allows for
localized delivery of at least one therapeutic agent to specific
cells or tissues, such as one or more tumors. In certain
embodiments, administration of at least one compartmentalized
therapeutic frozen particle composition is directed to one or more
adjacent, metastatic, or affected tissues including lymph nodes,
lymphatic vessels, blood vessels, and organs (e.g. liver, lung, and
kidney).
[1350] The size, shape or delivery velocity of the at least one
compartmentalized frozen particle composition can be controlled in
order to deliver the at least one particle composition to a desired
location or penetration depth. In certain embodiments, the
compartmentalized frozen particle composition includes at least one
therapeutic agent (e.g. a cytotoxic agent) that is delivered
intracellularly, intercellularly, or into the lumen of vasculature,
lymphatics, alveoli, bladder, intestine, lungs or into a specific
tissue (e.g. endoderm, smooth muscle, skeletal muscle,
prostate).
[1351] In one example, hollow bullet-shaped frozen particle
compositions containing a prodrug, such as capecitabine, can be
delivered intracellularly to tumor cells (e.g. colon carcinoma)
where capecitabine is metabolized to 5-fluorouracil, an active
cytotoxic agent. Administration of at least one frozen particle
composition including capecitabine specifically to tumor cells and
optionally to proximal tissues allows for the potential to increase
the therapeutic dose to tumor cells, while reducing systemic
exposure (which can lead to toxicity and side effects, including
angina and myocardial infarction, diarrhea, nausea, neutropenia,
anemia and thrombocytopenia).
[1352] Alternatively, in one embodiment, intracellular delivery of
at least one frozen particle composition including capecitabine
that is encapsulated in biodegradable polymeric nanoparticles,
releases capecitabine in a pH-dependent manner. (See for example,
Shenoy et al, Pharm. Res. vol. 22, pp. 2107-2114 (2005), which is
incorporated herein by reference). Since tumor cells generally have
a lower pH than non-tumor cells, the capecitabine is released in
higher amounts in the tumor environment.
[1353] Alternatively, in one embodiment, at least one frozen
particle includes capecitabine and one or more polymeric
nanoparticles composed of at least poly(.epsilon.-caplactone)
(PCL), a non-pH sensitive polymer that is able to release
capecitabine as the frozen particle melts or sublimates. (See, for
example, Shenoy et al, Ibid.).
Example 17
Compartmentalized Frozen Particle Therapeutic Compositions
Including Reinforcement Agents for Transdermal Administration
[1354] Frozen particle compositions that include at least one
therapeutic agent in one or more distinct regions of the particles
are useful for transdermal administration of at least one
therapeutic to various layers of the skin or to underlying tissues,
organs and structures. For example, treatment of certain skin
disorders, such as psoriasis, is currently limited to topical
administration of a therapeutic agent (e.g. coal tar,
corticosteroids, vitamin D.sub.3 analogs, or retinoids), systemic
treatments (e.g. methotrexate, cyclosporin and retinoids), or UV
irradiation (e.g. phototherapy) (See, for example,
en.wikipedia/wiki/psoriasis2008, which is incorporated herein by
reference). None of these current treatments are fully
effective.
[1355] In one embodiment, at least one frozen particle composition
including one or more psoriasis therapeutic agents located in one
or more gradation layers of concentration, or as a coating on the
particle is administered to the epidermis, dermis or hypodermis
layer by controlling specific parameters, such as particle
hardness, size, shape, reinforcement agent, or velocity. For
example, frozen particle compositions including reinforced hydrogen
oxide are propelled toward at least one biological tissue by
"flash-boiling" liquid nitrogen to create nitrogen gas and propel
the particle compositions by explosive force. The frozen particle
compositions are reinforced with plant matter (such as silk fibers,
or collagen fibers), or spun metallic fibers (such as tungsten,
iron, manganese, carbon, titanium, or steel). The one or more
frozen particle compositions are directed with a hose and nozzle
device onto psoriatic skin. In addition, the frozen therapeutic
particle compositions can be delivered to the dermis to further
impact any pathogenic T cells or cytokines associated with the
condition.
[1356] In one embodiment, hollow bullet-shaped frozen particle
compositions containing one or more biological agent, for example
etanercept (as an anti-TNF-.alpha. therapy), are administered to
the dermal layer underlying areas of psoriatic skin. One or more
other therapeutic agents can be combined with the one or more
biological agent on the same frozen particle, or on different
frozen particles for administration. For example, cytotoxic or
cytostatic agents are administered to cells associated with
psoriasis, including T1 cells, T.sub.H17 cells, dendritic cells,
neutrophils or keratinocytes. (See, for example, Sabat et al, Exp.
Derm. vol. 16, pp. 779-798 (2007), which is incorporated herein by
reference). For example, therapeutic agents such as anti-CD3,
anti-IL-23, anti-IL-17 or cyclosporin are included in one or more
frozen particles to further treat psoriasis in the dermis or
epidermis.
Example 18
Compartmentalized Frozen Particle Therapeutic Compositions
Including Explosive Materials
[1357] Hollow frozen particle compositions including one or more
reinforcement agents and hydrogen oxide are filled with solid
carbon dioxide. The hollow frozen particle compositions are useful
for destroying, debriding, ablating, or eliminating unwanted cells
or tissues such as fat, bone or tumor cells. In one embodiment, the
hollow frozen particle compositions containing a solid carbon
dioxide core produces an explosive force as the particle sublimates
or melts during administration of the frozen particle compositions.
The explosive force fragments, abrades, or destroys cells or
tissues.
[1358] At least one sub-group of the frozen particle composition
treatment course includes one or more of an antibiotic or other
anti-microbial agent; one or more anti-inflammatory drugs; one or
more anesthetics or analgesics; or one or more vasoconstrictors.
Targeted delivery of hollow frozen particle compositions to
unwanted cells or tissues is regulated by controlling, for example,
frozen particle hardness, size, shape, reinforcement agents or
explosive agents, and velocity. One or more frozen particle
compositions are administered to at least one biological tissue by
external (e.g. transdermal) methods, or internal (e.g.
laparoscopic) methods. In one embodiment, a device (e.g. tube and
spray nozzle) is integrated for administration of the one or more
frozen particle compositions.
[1359] Compartmentalizd frozen particle compositions are useful for
destroying adipocytes or fatty tissue. Present treatments include
liposuction, which is performed with a cannula attached to an
aspirator that is inserted through small incisions proximal to
unwanted fat and the cannula are drawn over the fat to dislodge it
and aspirate it (See, for example,
en.wikipedia.org/wiki/Liposuction2008, which is incorporated herein
by reference).
[1360] In one embodiment, a tube and spray nozzle is integrated
with the cannula for administration of frozen particles containing
a solid carbon dioxide core and optionally, one or more therapeutic
agents. For example, the operator sprays frozen particle
compositions containing carbon dioxide toward the adipocytes or
fatty tissue in order to remove or destroy the tissue. Next, the
treated tissue is aspirated with the cannula.
[1361] In one embodiment, a laparoscope can be used with the
delivery device to allow visualization of the fatty tissue as well
as precise delivery of the one or more frozen particle
compositions. In certain embodiments, the frozen particle
compositions also include lidocaine or ibuprofen in order to
minimize pain and inflammation often associated with liposuction.
In certain embodiments, at least one vasoconstrictor, such as
epinephrine, is included in the one or more frozen particles in
order to minimize bleeding. In certain embodiments, antibiotics,
such as penicillin or sulfonamide, are included to reduce
infection.
[1362] Alternatively, frozen particle compositions including a
solid carbon dioxide core, one or more antibiotics, analgesics,
anti-inflammatory drugs or vasoconstrictors are delivered
transdermally to adipose tissue by spraying the particle
compositions as described herein, at the appropriate velocity to
penetrate the epidermis, dermis or hypodermis. Following treatment
of adipocytes or fatty tissue with the one or more frozen
particles, liposuction is performed to remove the treated cells or
tissues. In one embodiment, adipocytes are selectively treated with
minimal effect on the underlying muscle cells, which reduces
bruising or bleeding.
Example 19
Compositions and Methods of Administering Frozen Particles
Including One or More Adhesive Agents and One or More Biological
Remodeling Agents
[1363] Frozen particles including hydrogen oxide, carbon dioxide,
dimethylsulfoxide or a buffer (e.g. HEPES, Ringer's solution,
sodium citrate, sodium phosphate, etc.) are formulated with at
least one adhesive agent such as cyanoacrylate, polyethylene glycol
polymers or albumin plus glutaraldehyde.
[1364] Frozen particle compositions including at least one adhesive
agent are utilized in conjunction with standard methods to achieve
hemostasis in patients undergoing surgery, for example, to repair
large blood vessels such as the aorta, femoral or carotid arteries.
Frozen particle compositions including bovine albumin and
glutaraldehyde (BIOGLUE.RTM., CryoLife, Inc., Kennesaw, Ga.) are
utilized, for example, in repair of an aortic dissection or other
blood vessel repair.
[1365] Frozen particle compositions including hydrogen oxide,
glutaraldehyde, and bovine albumin are produced as described herein
at other sections. In an embodiment, various different subsets of
frozen particle compositions are produced, for example, one subset
includes frozen hydrogen oxide particles including glutaraldehyde,
while another subset is produced that includes frozen hydrogen
oxide particles including bovine albumin.
[1366] In an embodiment, a single set of frozen particle
compositions are produced, for example, including frozen hydrogen
oxide particles including both glutaraldehyde and bovine
albumin.
[1367] In an embodiment, a set of frozen particle compositions are
produced, for example, that includes compartmentalized particles
wherein both glutaraldehyde and bovine albumin are present on a
particular particle, but each is partially or wholly sequestered in
a separate compartment of the particular particle. Some examples of
compartmentalized frozen particles are described herein at other
sections.
[1368] In an embodiment, frozen particles include bovine albumin in
a mass ratio of weight per volume of approximately 5%,
approximately 10%, approximately 15%, approximately 20%,
approximately 25%, approximately 30%, approximately 35%,
approximately 40%, approximately 45%, approximately 50%,
approximately 55%, approximately 60%, approximately 65%,
approximately 70%, approximately 75%, or any value
therebetween.
[1369] In an embodiment, frozen particles include glutaraldehyde in
a mass ratio of weight per volume of approximately 1%,
approximately 2%, approximately 3%, approximately 4%, approximately
5%, approximately 6%, approximately 7%, approximately 8%,
approximately 9%, approximately 10%, approximately 11%,
approximately 12%, approximately 15%, approximately 16%,
approximately 17%, approximately 18%, approximately 19%,
approximately 20%, or any value therebetween.
[1370] One or more sets of frozen particle compositions including
hydrogen oxide, glutaraldehyde, and/or bovine albumin, as described
herein, are administered to the false lumen of the dissected aorta
or other blood vessel in need of repair, at the distal and proximal
anastomotic sites.
[1371] In an embodiment, a set of frozen particle compositions
including bovine albumin and glutaraldehyde is administered alone
or in conjunction with (sequentially or simultaneously with) other
frozen particle compositions that optionally include, for example,
one or more of at least one therapeutic agent, at least one
reinforcement agent, at least one explosive material.
[1372] In an embodiment, multiple sets of frozen particle
compositions, including bovine albumin and glutaraldehyde on
separate particles are administered simultaneously or sequentially
to the biological tissue. These multiple sets of frozen particle
compositions are optionally administered simultaneously or
sequentially with other frozen particle compositions that include,
for example, one or more of at least one therapeutic agent, at
least one reinforcement agent, or at least one explosive
material.
[1373] Depending on the thickness of the blood vessel to be
repaired, as well as other factors, an adhesive layer is
administered with a thickness of approximately 0.1 mm,
approximately 0.2 mm, approximately 0.3 mm, approximately 0.4 mm,
approximately 0.5 mm, approximately 0.6 mm, approximately 0.7 mm,
approximately 0.8 mm, approximately 0.9 mm, approximately 1.0 mm,
approximately 1.5 mm, approximately 2.0 mm, approximately 2.5 mm,
approximately 3.0 mm, approximately 3.5 mm, approximately 4.0 mm,
approximately 4.5 mm, approximately 5.0 mm, approximately 6.0
mm.
[1374] Optionally, subsequent to repair of the distal and proximal
ends of the blood vessel, one or more support structural materials
are inserted to replace damaged blood vessel sections. Some
examples of structural material that can be utilized are described
herein at other sections. For example, some non-limiting examples
of structural material include one or more of tubing (such as
plastic or rubber tubing, e.g. polyethylene terephthalate or
polytetrafluoroethylene), a stent (optionally including one or more
therapeutic agents), a matrix (such as extracellular matrix
components, or an artificial or synthetic matrix), a rod or other
physical support.
[1375] Following insertion of the optional support structure, one
or more sets of frozen particle compositions are administered to
the repaired blood vessel to secure the structure or assist in
modulating hemostasis. One or more sets of frozen particle
compositions are also optionally administered to the junctions
between the support structure and the vasculature.
Example 20
Compositions and Methods of Administering Frozen Particles
Including One or More Adhesive Agents and One or More Biological
Remodeling Agents
[1376] Surgical incisions, burns, and other traumatic injuries
result in damage to the dermis or hypodermis skin layers. Frozen
particles including at least one adhesive agent, and optionally one
or more of a growth factor, an anesthetic, or an antibiotic are
administered to the biological tissue to secure would closure,
including securing skin grafts. The frozen particles are
administered alone or in conjunction with surgical staples or
sutures.
[1377] In an embodiment, one or more frozen particles including
thrombin (e.g., activated thrombin) or fibrinogen are administered.
As described in other sections herein, thrombin and fibrinogen can
be included as part of a single frozen particle (including, for
example, provided in compartments of a single frozen particle), a
single set of frozen particles, or separately as part of different
frozen particles or different sets of frozen particles. As
described herein, if multiple sets of frozen particles are
administered, the sets can be administered simultaneously or
sequentially.
[1378] In an embodiment, one or more frozen particles including at
least one adhesive agent include a biodegradable polymer that
encapsulates at least one therapeutic agent (such as a growth
factor, antibiotic, anesthetic or other agent). For example,
poly(6-caprolactone) (PCL) allows for controlled or sustained
release of a therapeutic agent for a specific location (See, for
example, Shenoy et al, Ibid., which is incorporated herein by
reference).
[1379] In an embodiment, one or more frozen particles include
activated thrombin at a concentration of approximately 0.5 IU/mL,
approximately 1.0 IU/mL, approximately 1.5 IU/mL, approximately 2.0
IU/mL, approximately 2.5 IU/mL, approximately 3.0 IU/mL,
approximately 3.5 IU/mL, approximately 4.0 IU/mL, approximately 4.5
IU/mL, approximately 5.0 IU/mL, approximately 5.5 IU/mL,
approximately 6.0 IU/mL, approximately 6.5 IU/mL, approximately 7.0
IU/mL, approximately 7.5 IU/mL, approximately 8.0 IU/mL,
approximately 8.5 IU/mL, approximately 9.0 IU/mL, or any value
therebetween.
[1380] In an embodiment, one or more frozen particles include
fibrinogen at a concentration of approximately 20 mg/mL, 30 mg/mL,
40 mg/mL, 50 mg/mL, 60 mg/mL, 70 mg/mL, 80 mg/mL, 90 mg/mL, 100
mg/mL, 110 mg/mL, 115 mg/mL, 120 mg/mL, 130 mg/mL, 140 mg/mL, 150
mg/mL, or any value therebetween.
[1381] Since activated thrombin reacts with fibrinogen by way of
proteolysis to form a fibrin adhesive, the concentration of either
fibrinogen or thrombin can be increased or decreased, depending on
the desired goal of wound closure. (See, e.g., Spotnitz et al.
Transfusion, vol. 48, pp. 1502-1516 (2008); Evans et al., Braz. J.
Urol. vol. 32, pp. 131-141 (2006), each of which is incorporated
herein by reference.) For example, if a skin graft is involved in
the wound repair and a slow rate of adherence is desired in order
to accurately place the graft on the wound, the concentration of
either thrombin or fibrinogen can be reduced. Alternatively,
separate sets of one or more frozen particles can be administered,
wherein the concentration of at least one adhesive agent varies
within a set or between the separate sets of frozen particles.
Optionally, one or more frozen particles can include at least one
proteolytic inhibitor, such as aprotinin, in order to prolong the
fibrin adhesive effect. (See, e.g., Spotnitz et al, Ibid., which is
herein incorporated by reference).
[1382] Optionally, one or more of the frozen particles includes at
least one detection material (e.g., a non-reactive, biodegradable
dye or non-toxic contrast agent) that allows for visual detection
of application of the one or more frozen particles. In an
embodiment, the one or more frozen particles including at least one
detection material also include at least one other agent (e.g., at
least one adhesive agent, or at least one therapeutic agent). (See,
e.g., worldwide web at
kolorjectchemicals.com/natural-food-color.html, visited on Nov. 25,
2008, which is incorporated herein by reference.)
[1383] Optionally, frozen particles are administered that include
one or more growth factor (e.g., keratinocyte growth factor,
vascular endothelial growth factor A, epidermal growth factor,
fibroblast growth factor, or hepatocyte growth factor) to promote
engraftment. (See, for example, Nolte et al, Cells Tissue Organs,
vol. 187, pp. 165-176 (2008); Boateng et al., J. Pharm. Sci. vol.
97, pp. 2892-2923 (2008), each of which is incorporated herein by
reference). In addition or instead of these growth factors, one or
more frozen particles include one or more of collagen, hyaluronic
acid, glycosaminoglycans, or other extracellular matrix components,
at least one of which is encapsulated in a PCL polymer. (See, for
example, Boateng et al., Ibid, which is incorporated herein by
reference.)
[1384] In an embodiment, compartmentalized frozen particles
including one or more of activated thrombin, fibrinogen, antibiotic
(e.g., minocycline, gentamycin, oxoflacin, or tetracycline), or
PCL-encapsulated extracellular matrix or growth factor are
administered to a wound.
[1385] In an embodiment, one or more frozen particles include one
or more cells (e.g., pluripotent stem cells, mesenchymal stem
cells, fibroblasts, keratinocytes, dermal progenitor cells) to
assist in wound repair, including skin engraftment. For example,
dermal fibroblasts suspended in cryogenic media (e.g., containing
10% dimethylsulfoxide) are included in one or more frozen
particles. In the same or different frozen particle, one or more of
at least one growth factor, at least one extracellular matrix
component, or at least one adhesive agent are included. Optionally,
one or more of the agents included in the frozen particles are
encapsulated by PCL or another polymer. The frozen particles can be
administered simultaneously or sequentially.
[1386] In an embodiment, several different sets of frozen particles
are administered in order to establish layers of, for example,
extracellular matrix, fibroblasts, fibrin sealant, and
keratinocytes can be administered in multiple layers with or
without an additional skin graft. In an embodiment, the skin graft
itself has been derived artificially or synthetically, at least in
part, by administration of frozen particles including various skin
components to at least one biological tissue or a synthetic matrix
(e.g., biodegradable sponge or polymer matrix).
[1387] Optionally, as in the case of burns or other wounds in which
necrotic tissue is present, frozen particles are administered to
debride tissue prior to would closure or skin engraftment. Frozen
particles including one or more of at least one antibiotic (e.g.,
neomycin, polymixin B, or gramicidin), or at least one anesthetic
(e.g., lidocaine). As described herein at other sections,
debridement of cells or tissue is regulated by several factors,
including characteristics of the one or more frozen particles
(e.g., size, shape, or constitution of any particular frozen
particle), as well as characteristics of administration of the one
or more frozen particles (e.g., velocity of delivery, angle of
delivery, quantity of particles delivered, or rate of
delivery).
[1388] In an embodiment in which tissue is debrided, a device is
utilized to administer the one or more frozen particles, as
described herein at other sections. In an embodiment, a tube and
nozzle is utilized to administer the one or more frozen particles,
with an optional aspirator tube to remove liquid and tissue as
debridement occurs.
Example 21
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Remodeling Agents, One or More
Therapeutic Agents, One or More Adhesive Agents, and One or More
Reinforcement Agents for Tissue Reconstruction
[1389] Frozen particle compositions including one or more of a
reinforcement agent, antibiotic, therapeutic agent, polymer,
adhesive, stem cell, or progenitor cell are utilized for debriding
damaged or necrotic tissue, such as bone and cartilage.
Subsequently, one or more frozen particle compositions as described
are utilized for reconstructing the tissue, in addition to or
instead of one or more frozen particle compositions including one
or more of a growth factor, progenitor cell or stem cell.
[1390] For example, joint restructuring or replacement is a common
surgical procedure for joints such as knee or hip joints. Knee
replacement surgery is performed as a partial or total knee joint
replacement. Standard knee replacement generally includes replacing
or supplementing diseased or damaged joint surfaces with bone
grafts (e.g., autologous or cadaveric bone grafts) or synthetic
materials (e.g., metal, plastic, or rubber substrates).
[1391] Optionally, computer systems are used to model the bone
defect, based on imaging studies (e.g., x-ray, computed tomography
(CT), or other imaging). Among other things, imaging the bone or
other tissue (e.g., cartilage), allows for assessment of the
defect, or analysis of the present joint structure, allows for
assistance in designing repair or replacement of the joint, and
provides guidance for delivery of the frozen particle compositions.
In certain instances, the frozen particle compositions are
delivered by way of a piezoelectric or inkjet printer device that
is directly or indirectly under the control of a computer
system.
[1392] In an embodiment, a CT scan is used to develop a
three-dimensional image of the joint to be reconstructed. For a
knee joint, for example, regions from the distal femur and proximal
tibia, including synovial and cartilage, can be imaged for
assessment. Computer systems and methods for designing and
repairing the joint(s) can also be used for comparing the present
state of the subject's joint with that of a healthy individual.
Thus, the repair may include reconstructing or restructuring the
joint according to healthy or undamaged joints.
[1393] Optionally, a computer system also controls a robotic arm or
other automated instrument containing a piezoelectric or inkjet
printer device, or sprayer for administration of one or more frozen
particle compositions in the reconstruction of the joint. In
certain instances, the subject's damaged or diseased joint is
ablated or debrided with one or more frozen particle compositions
in addition to or instead of reconstructing the joint. In certain
instances, one or more frozen particles are delivered to a
substrate (e.g., natural, artificial, or synthetic materials) used
in reconstructing the subject's knee joint. In certain instances,
the substrate includes an artificial knee joint or a cadaveric knee
joint.
[1394] In the case where the subject's joint is ablated or
debrided, one or more frozen particle compositions are administered
to the subject's joint (optionally with assistance of a computer
system). The ablation or debridement may be performed before,
during, or subsequent to the administration of one or more frozen
particle compositions related to stabilizing the joint or
reconstructing the joint. For example, frozen particle compositions
including reinforcement agents (e.g., silica beads, fiberglass,
polyethylene glycol) are propelled toward the subject's knee joint
at or to a predetermined velocity that allows for delivery of the
compositions into the various layers of the joint (i.e., skin,
subcutaneous layers, synovial membrane, etc.).
[1395] In an embodiment, an arthroscopic device is utilized for
delivery of one or more frozen particle compositions to the knee
joint. A computer system can assist a surgeon in ablating or
debriding the cartilage and/or bone to the proper depth by
delivering the frozen particle compositions at a predetermined or
preselected set of parameters. The predetermined or preselected
parameters include, but are not limited to, size of frozen particle
compositions, shape of frozen particle compositions, constitution
of frozen particle compositions, velocity at which frozen particle
compositions are delivered, angle at which frozen particle
compositions are delivered, timing for delivery of specific frozen
particle compositions, or programs for cycling any one or more
parameters. In an embodiment, ablation is performed on a knee joint
with guidance provided by a computer system or imaging apparatus.
During or subsequent to ablation, frozen particle compositions
containing therapeutic agents (such as at least one antibiotic or
anti-inflammatory agent) are administered to the joint.
[1396] In an embodiment, the joint is reconstructed by utilizing a
computer system for imagine or modeling the joint. Optionally, the
computer system is directly or indirectly linked to a sprayer or
piezoelectric or inkjet printer device capable of administering one
or more frozen particle compositions. In certain instances, the
frozen particle compositions administered to reconstruct the joint
include scaffolding materials of natural, artificial, or synthetic
origin (examples of specific agents include, but are not limited
to, antibodies; growth factors; e.g., bone morphogenic protein;
polymers; e.g., polylactic acid, polylactic acid-co-glycolic acid;
or adhesives; e.g., polyethylmethacrylate/tetrahydrofurfuryl
methacrylate, hydroxyapatite, etc.), or an amphiphilic polymer. In
one embodiment, the delivery of one or more adhesive agents or at
least one biological remodeling agents, includes at least one
temporally-regulated method. (See, e.g., Davies, et al. Advanced
Drug Delivery Reviews, vol. 60, pp. 373-387 (2008); or Kanczler et
al. Biomaterials, vol. 29, pp. 1892-1900 (2008), each of which is
incorporated herein by reference.)
[1397] In an embodiment, scaffolding materials solidify in situ at
physiological temperature and pH, and may include, but not be
limited to, calcium phosphate cement with a biocompatible gelling
agent and scaffold materials for cartilage regeneration (e.g.,
oligopoly-ethylene glycol fumarate,
polyN-isopropylacrylamideco-acrylic acid,
polyN-isopropylacrylamide-grafted gelatin, polyethylene oxide,
alginate, fibrin, PLGA-g-PEG, pluronics, calcium
phosphate/hyaluronic acid composites, hyaluronic acid gel and
chitosan. See, e.g., Hou et al., J. Mat. Chem. vol. 14, pp.
1915-1923 (2004), which is incorporated by reference herein.
[1398] Optionally, one or more frozen particle compositions
including scaffolding materials that promote adhesion of cell types
that produce bone or cartilage are administered to assist in
reconstructing the subject's joint. For example, integrin peptides
with the arginine-glycine-aspartic acid (RGD) sequence can be
covalently coupled with other scaffolding materials administered to
the joint. Integrins are capable of promoting adhesion of cells,
including osteoblasts, via their integrin receptors. See, e.g.,
Hou, et al., Ibid.
[1399] Optionally, one or more frozen particle compositions
including antibodies or antibody fragments are chemically coupled
with scaffold polymers that among other things, promote binding and
retention of specific cell types within the scaffold, are
administered to the subject's knee or a substrate used in
reconstructing the knee. For example, anti-integrin
.alpha..sub.V.beta..sub.3 antibodies recognize endothelial cells,
and anti-integrin .alpha..sub.5 antibodies recognize chondrocytes,
both of which cell types can assist in reconstructing the joint.
See, e.g., Hou et al, Ibid.
[1400] Optionally, one or more frozen particle compositions
including one or more growth factors that are capable, for example,
of promoting cell growth and/or cell differentiation are
administered in reconstructing the knee joint. For example, bone
morphogenic proteins, fibroblast growth factors, vascular
endothelial growth factors, or other factors are encapsulated in
polymer particles (e.g., vesicles) that form at least part of a
scaffold to support reconstruction of the joint. See, e.g., Davies
et al., Ibid. In an embodiment, one or more growth factors support
the infiltration or growth of osteocytes, chondrocytes, or vascular
cells.
[1401] In an embodiment, one or more frozen particle compositions
including one or more of a progenitor cell, stem cell, osteoblast,
chondrocyte, or endothelial cell are administered. In an
embodiment, one or more subsets of frozen particle compositions
include, but are not limited to compositions containing one or more
of a scaffolding material, adhesive agent, or growth factor. In an
embodiment, one or more subsets of frozen particle compositions are
administered to the subject's joint simultaneously, sequentially,
or cyclically.
[1402] In an embodiment, reconstruction of the joint is conducted
by administering one or more subsets of frozen particle
compositions through interaction or consultation with a computer
system. In an embodiment, administration of one or more frozen
particle compositions or one or more subsets of frozen particle
compositions occurs in a stepwise fashion according to one or more
parameters including, but not limited to, size of frozen particle
compositions, shape of frozen particle compositions, constitution
of frozen particle compositions, velocity at which frozen particle
compositions are delivered, angle at which frozen particle
compositions are delivered, timing for delivery of specific frozen
particle compositions, or programs for cycling any one or more
parameters.
[1403] In an embodiment, the joint is debrided, and the surface is
prepared for reconstruction. Additionally, one or more frozen
particle compositions or one or more subsets of frozen particle
compositions are administered containing one or more of a
scaffolding material, an adhesive agent, a therapeutic agent, a
reinforcement agent, or an explosive agent. For example, calcium
phosphate cement with a biocompatible gelling agent are included
with one or more frozen particle compositions. In the same or
different frozen particle compositions, growth factors (such as
vascular endothelial growth factors or bone morphogenic factors)
are included. In addition, in the same or different frozen particle
compositions, osteoblast cells or osteoblast precursor cells are
administered to the subject's joint or a substrate used for
reconstructing the joint. In the same or different frozen particle
compositions, at least one scaffold material, such as a polymer, is
administered to the joint or a substrate used for reconstructing
the joint. For example, oligopoly-ethylene glycol fumarate
optionally with a chondrocyte growth factor (e.g., fibroblast
growth factor) are included in one or more frozen particle
compositions. In the same or different frozen particle
compositions, frozen particle compositions including chondrocytes
or condrocyte progenitor cells (e.g., mesenchymal stem cells) are
administered to the joint.
[1404] In an embodiment, one or more steps of assessing the joint,
preparing the joint, debriding or abrading the joint, or
reconstructing the joint are aided by use of a computer system,
including but not limited to CT imaging, computer-aided design
(CAD), or computer-aided surgery (CAS). See, e.g., Bradley et al.,
Arch. Otolaryngol. Head Neck Surg. Vol. 34, pp. 1080-1084 (2008),
which is incorporated by reference herein.
Example 22
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents and One or More
Biological Remodeling Agents
[1405] Frozen particles containing one or more biological adhesive
agents (for example, bispecific antibodies or bispecific proteins),
are used to bind cells or tissues specifically to therapeutic
targets, such as endothelial cells, leukocytes, epithelial cells,
cancer cells, extracellular matrices, vasculature, lymphatics,
tumors, and other tissues. For example, one or more frozen
particles containing at least one bispecific receptor, antibody,
ligand, or fusion proteins of one or more of receptors, antibodies,
or ligands are used to selectively bind or adhere leukocytes, such
as macrophages, monocytes, T cells, natural killer cells (NK
cells), granulocytes, or other cells to target tissues,
extracellular matrices, or other cell types (e.g., cancer cells,
endothelial cells, or epithelial cells).
[1406] Moreover, one or more frozen particles optionally contain at
least one biological adhesive agent and at least one leukocyte in
separate sectors. In one embodiment, the sector includes a
compartment.
[1407] In one embodiment, one or more biological adhesive agent is
bound to a leukocyte (or other cell) in vitro prior to
incorporation of the cell plus biological adhesive into the one or
more frozen particle compositions. Optionally, one or more frozen
particle compositions including at least one biological adhesive or
at least one cell are delivered sequentially to a target tissue,
matrix, or cell type.
[1408] Examples of one or more biological adhesive agents are
disclosed herein at other sections, and include but are not limited
to mammalian cell surface proteins, and glycoproteins. For example,
adhesion molecules include CD44, immunoglobulin (Ig) superfamily
members, integrins, cadherins, and selectins. These or other
factors that are included in the disclosure specifically bind to
protein or macromolecule ligands (e.g., intercellular adhesion
molecule (ICAM), vascular cell adhesion molecule (VCAM),
fibronectin, and hyaluronate), MADCAM, LFA-1, and others. Other
cell surface receptors are included as biological adhesive agents,
including but not limited to immunoglobulin Fc receptors (FcR),
complement receptors (CR), and surface immunoglobulin (sIg).
Example 23
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents for Administration
to Tumor Tissue
[1409] Frozen particles containing one or more biological-based
adhesive agents are used to deliver and bind immune effector cells
to primary or metastatic tumor cells, as well as tumor-associated
stroma or extracellular matrices. Macrophages or monocytes that
have the potential to kill tumor cells, and present
tumor-associated antigens are recognized by antibodies that bind
integrin receptors, such as VLA-4, .beta.-1, .beta.-2, Fc.gamma.
receptor I (CD64) or by cell adhesion peptides (e.g., YRGDS,
YEILDV). (See, for example, Martin-Manso et al., Cancer Res., vol.
68, pp. 7090-7099 (2008); Wagner et al., Biomat., vol. 25, pp.
2247-2263 (2006); each of which is incorporated herein by
reference). In addition, lymphocytes (such as T cells or B cells),
as well as natural killer cells are capable of directed killing of
tumor cells, and are included in specific embodiments disclosed
herein.
[1410] Biological adhesive agents, including a bispecific antibody,
such as anti-CD64 binding domain (e.g., single chain Fv (SCFv)) is
fused to a second binding domain that recognizes a tumor-associated
antigen (e.g., CA-125 (mucin 16), or melanoma-associated antigen
(MAGE)). Mucin 16 binds macrophages to ovarian cancer cells, while
MAGE binds macrophages to melanoma cancer cells. Generation,
including design, construction, and production, of bispecific
antibodies is generally known in the art. (See, for example, USPTO
Application Publication No. 20080305105; Kufer et al., Trends in
Biotech., vol. 22, pp. 238-244 (2004); each of which is
incorporated herein by reference.)
[1411] Macrophage or monocyte cells are obtained from the
peripheral blood of cancer patients or subjects. Monocytes are
purified from peripheral blood leukocytes (standard reagents and
protocols are available from, for example, StemCell Tech., Inc.,
Vancouver, B.C., Canada). Monocytes are activated by treatment in
vitro with cytokines, such as interferon-.gamma.. (See, for
example, Kufer et al., Ibid.) Production of macrophage cells that
are cytotoxic for tumor cells is described, for example, in
Martin-Manso et al., Ibid. Cytotoxic macrophage cells are bound in
vitro to a bispecific antibody (e.g., antibody that recognizes CD64
or MAGE), prior to incorporation into one or more frozen particle
compositions for administration to a melanoma tumor.
[1412] Briefly, bispecific antibodies at 10-100 micrograms/mL in
RPMI 1640 media, pH 7.4 (Invitrogen Corp., Carlsbad, Calif.), are
incubated with monocyte cells for 1-4 hours at 5.degree.-37.degree.
C. Monocyte cells with bound bispecific antibodies are washed by
centrifugation and incorporated into one or more frozen particle
compositions containing dimethylsulfoxide (10% vol/vol), RPMI 1640
media, and human serum (20% vol/vol).
[1413] One or more frozen particle compositions containing one or
more monocyte cells, one or more biological adhesive agents, and
media are delivered directly to tumor tissue by a device (for
example, a spray device). Depending on various factors, including
but not limited to, size of tumor, presence of metastatic tumor
tissue, extent of any metastatic tissue, type of tissue of origin
for the tumor, location of tumor, condition of the subject, or
other factors, the depth of frozen particle penetration can be
predicted or determined through design or alteration of frozen
particle composition velocity, size, shape, and constituency of the
one or more frozen particles.
Example 24
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents for Administration
to Tumor Tissue
[1414] Immune effector cells (including monocytes, macrophages,
natural killer cells, or lymphocytes) plus bound bispecific
antibodies are delivered to tumor tissue, for example, at a site or
organ (e.g. lung, liver) using a device (such as an endoscope,
incluindg a laparascope or thoracoscope). In one embodiment, a
particle spraying device is introduced through a trocar and guided
by way of an endoscope, delivers the frozen particle compositions
including at least one immune effector cell with at least one
biological adhesive to the target site. In one embodiment, the
target site includes tumor tissue. In at least on embodiment, the
target site includes tissue surrounding a tumor. In one embodiment,
the target site includes tissue suspected of being cancerous. In
one embodiment, the target site includes primary tumor tissue. In
one embodiment, the target site includes metastatic cancer
tissue.
[1415] In one embodiment, frozen particle compositions including at
least one biological adhesive and at least one immune effector cell
are administered as an adjunct therapy following surgery to resect
diseased tissue, chemotherapy, radiation treatment, or other
therapy. For example, frozen particle compositions including at
least one biological adhesive that recognizes monocytes (e.g.,
anti-CD64) and MAGE are administered to tissue surrounding the
surgical site, including lymph nodes or sites of suspected or
anticipated metastasis.
Example 25
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents to Melanoma Cells
and Tumor-Associated Endothelial Cells
[1416] At least one biological adhesive recognizing one or more
integrin present on melanoma cells or tumor endothelial cells is
used to bind immune effector cells to melanoma cells or
tumor-associated endothelial cells. For example, one or more
antibodies specific for the integrin .alpha..sub.v.beta..sub.3 and
CD3 (a signaling part of the T cell antigen receptor) can be used
in conjunction with cytotoxic T cells derived from melanoma
subjects. See, for example, Berger et al., J. Clin. Invest. vol.
118, pp. 294-305 (2008), which is incorporated herein by
reference.
[1417] One or more frozen particle compositions containing
anti-.alpha..sub.v.beta..sub.3, anti-CD3, or cytotoxic T cells bind
to melanoma cells directly or indirectly following binding to tumor
neovasculature endothelium and extravasation. See, for example,
Mahabeleshwar et al., Ibid. In one embodiment, the one or more
frozen particle compositions are administered in multiple
dimensions (e.g., x, y, z coordinates) to melanoma cells,
neovasculature, and adjacent tissues (which may or may not be
malignant). In one embodiment, primary tumor cells, metastatic
tumor cells, neovasculature, and adjacent lymphatic ducts and lymph
nodes are targeted. One or more frozen particle compositions
delivered to the epidermis, dermis, and subcutaneous layers of a
subject target melanoma cells in radial, vertical, and metastatic
modes of growth. See, for example, Mahabeleshwar et al, Ibid.
[1418] In one embodiment, administration of the one or more frozen
particle compositions in three dimensions is conducted with a
computer-guided spraying device. The computer-guided device uses
one or more computer systems, or one or more computer programs to
derive or obtain data to predict or generate one or more frozen
particle compositions based on specific characteristics. For
example, the one or more frozen particle compositions are predicted
or generated based on particle hardness, shape, size, constituency,
or other factors. The one or more frozen particle composition
administration is predicted or generated based on number of frozen
particle compositions administered for any particular round of
delivery, the velocity of delivery, the angle of delivery, the
number of rounds of delivery of the same or different frozen
particle compositions, the type of tissue receiving the frozen
particle compositions, the condition of the tissue receiving the
frozen particle compositions, and other factors. In this manner,
the one or more frozen particle compositions are administered to a
particular target tissue, and to a particular desired depth or
breadth.
Example 26
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents to Melanoma
Cells
[1419] One or more frozen particle compositions including one or
more biological adhesive agents capable of specifically binding
melanoma tumor cell surface receptors, including at least one
receptor capable of signaling or initiating apoptosis are
administered to melanoma cell's. For example, at least one
biological adhesive agent including at least one bispecific protein
that recognizes melanoma tumor cell antigens (e.g., MAGE), as well
as a pro-apoptotic cell surface receptor (e.g., death receptor 5
(DR5)) is delivered to melanoma cells for induction of
apoptosis.
[1420] In one embodiment, binding of DR5 by an agonistic monoclonal
antibody or apoptosis ligand 2/TNF-related apoptosis-inducing
ligand (e.g., Apo2L/TRAIL) initiates signaling that leads to
apoptotic death of the tumor cell. See, for example, Ashkenazi,
Nat. Rev. Drug Discov., vol. 7, pp. 1001-1012 (2008). Some examples
of agonistic antibodies that are capable of inducing apoptosis on
tumor cells include, but are not limited to, mapatumumab and
lexatumumab (Human Genome Sciences, Inc., Rockville, Md.; HGS),
Apomab (Genentech Inc., South San Francisco, Calif.), AMG655
(Amgen, Inc., Thousand Oaks, Calif.), CS-1008 (Daiichi Sankyo Co.,
Ltd., Tokyo), and LBY-135 (Novartis Int'l AG, Basel).
[1421] In one embodiment, a bispecific protein including anti-MAGE
binding domains (e.g., single chain Fv (SCFv)) and at least one
agonistic anti-DR5 binding domain (e.g., SCFv from Apomab;
Ashkenazi, Ibid) is administered in one or more frozen particle
compositions directly to melanoma cells, or delivered to
subcutaneous layers surround the melanoma cells.
[1422] In one embodiment, in addition to targeting primary tumor
cells, tissue known to be metastatic, or suspected to be metastatic
due to the epidemiology of the disease, are targeted. For example,
melanoma is known to metastasize to the brain. In one embodiment,
the brain receives one or more frozen particles alone or in
combination with surgery (e.g., craniotomy), based on imaging
studies done with computer-assisted tomography or magnetic
resonance imaging. Frozen particle compositions including
pro-apoptotic agonists or anti-MAGE binding proteins are used as
adjuvant therapy following surgery (e.g., open surgery,
stereotactic surgery, or stereotactic radiosurgery to remove or
destroy melanoma metastatic cells.
[1423] In one embodiment, minimally invasive computer assisted
surgery is used to remove tumor cells and tumor tissue, followed by
administration of one or more frozen particle compositions as
adjuvant therapy. For example, computer-aided surgery (CAS) is used
with stereotactic surgery systems to target tumor cells that have
infiltrated essential and/or highly vascularized brain tissues that
are considered inaccessible or inoperable by standard methods.
Example 27
Frozen Piercing Implements Utilized for Transdermal Delivery
[1424] In one embodiment, frozen hydrogen oxide piercing
implements, including microneedles, are utilized for transdermal
delivery of at least one agent.
[1425] In one embodiment, frozen microneedles with dimensions
ranging from approximately nanometers (nm) to approximately
millimeters (mm) can be made from hydrogen oxide ice Ic, and
optionally include one or more reinforcement agents. Frozen
microneedles can contain at least one therapeutic agent, including
but not limited to at least one antigen, vaccine, antibiotic,
analgesic, or other agent. The use of microneedles has been
reported to induce minor skin irritation. See, for example,
Wermeling, et al., Ibid. Such minor irritation may be desirable in
certain instances (i.e. for vaccination).
[1426] In one embodiment, microneedles made of frozen hydrogen
oxide, and optionally reinforced with at least one of polylactic
acid (L-PLA from BPI at Birmingham, Ala.) or polyvinyl pyrrolidone
(PVP), are cast in a first micromold fabricated using standard
photolithography and molding processes. For example, a frozen
microneedle mastermold is created in SU-8 photoresist (SU-8 2025,
Microchem, Newton, Mass.) by UV exposure to mold, for example,
pyramidal (square cross-section) piercing implements tapering from
a base measuring approximately 4 .mu.m to approximately 300 .mu.m
in width to a tip of approximately 0.33 .mu.m to approximately 25
.mu.m in width over a length of approximately 10 .mu.m to
approximately 2.0 mm. Next a frozen piercing implement second mold
is made, for example, from polydimethylsiloxane (PDMS, Sylgard 184,
Dow Corning, Midland, Mich.) by using the first micromold. Multiple
replicate molds can be produced by layering PDMS on the second
mold. (See Lee et al, Biomaterials, vol. 29, pp. 2113-2124 (2008)
which is incorporated herein by reference.) Finally, frozen
piercing implements are made, for example, by contacting liquid
hydrogen oxide optionally containing L-PLA and at least one
therapeutic or other agent in the molds, and freezing at
-20.degree. C. to -250.degree. C. to form frozen hydrogen oxide
piercing implements, such as microneedles.
[1427] In one embodiment, the frozen hydrogen oxide piercing
implements, such as microneedles, are in one or more phases
including at least one of: amorphous solid water, low density
amorphous ice, high density amorphous ice, very high density
amorphous ice, clathrate ice, hyperquenched glassy water, ice Ic,
ice II, ice III, ice IV, ice V, ice VI, ice VII, ice VIII, ice IX,
ice X, ice XI, ice XII, ice XIII, ice XIV, or ice XV.
[1428] In one embodiment, multiple micromolds contain one or more
arrays of multiple piercing implements, including one or more
microneedles. For example, in one embodiment, an array containing
120 microneedles in rows is made in a 9.times.9 mm configuration.
See, for example, Park et al, J. Control. Rel., vol. 104, pp. 51-66
(2005) which is incorporated herein by reference.
[1429] In one embodiment, frozen piercing implement arrays,
including microneedle arrays, are made by contacting, for example,
hydrogen oxide, one or more polymers, and at least one therapeutic
agent. For example, frozen piercing implement arrays, including
microneedle arrays, are made by utilizing at least one support
structure fabricated by patterning SU-8 epoxy photoresist onto
glass substrates and defining piercing implement shapes by
lithography. In one embodiment, at least one frozen piercing
implement includes at least one side-opening hollow implement. In
one embodiment, piercing implement tips are sharpened by reactive
ion etching. See, for example, Martanto et al, "Side-Opening Hollow
Microneedles for Transdermal Drug Delivery," 32nd Annual Meeting of
the Controlled Release Society, Florida, June, 2005 on the
worldwide web at:
mems.mirc.gatech.edu/msmawebsite.sub.--2006/publications/publication_list-
.html#c05, the content of which is incorporated herein by
reference.
[1430] In one embodiment, hydrogen oxide frozen piercing
implements, such as microneedles, include an optional reinforcement
agent, such as L-PLA, as well as at least one therapeutic or other
agent (including but not limited to bovine serum albumin (BSA) or
lysozyme). For example, reinforced hydrogen oxide solutions with
approximately 20% (weight %) bovine serum albumin (Sigma, St.
Louis, Mo.) are frozen at approximately 0.degree. C. to
approximately -250.degree. C. or lower in the micromolds to form at
least one array of frozen piercing implements, such as
microneedles.
[1431] In one embodiment, an array with 100 piercing implements,
including microneedles, delivers about 2000 .mu.g of BSA
transdermally. See, for example, Lee et al, Ibid. In one
embodiment, at least one piercing implement of the array includes a
frozen piercing implement. In one embodiment, all of the piercing
implements of the array include frozen piercing implements.
[1432] In one embodiment, frozen piercing implement arrays, such as
microneedle arrays, including BSA are inserted by hand into the
skin, then taped in place and left for time sufficient to deliver
at least part of the at least one agent (e.g., BSA). In one
embodiment, the array is allowed to stay in contact with the
substrate for at least approximately 1 second, approximately 5
seconds, approximately 10 seconds, approximately 20 seconds,
approximately 30 seconds, approximately 45 seconds, approximately 1
minute, approximately 2 minutes, approximately 5 minutes,
approximately 10 minutes, approximately 30 minutes, approximately 1
hour, approximately 2 hours, approximately 5 hours, approximately
24 hours, or any value therebetween or greater.
[1433] In one embodiment, frozen piercing implements, such as
microneedles, are inserted and ejected or released into the skin by
at least one mechanism including, but not limited to, breaking,
applying shear force, for example with a blade, or applying axial
force, for example, with plungers or pressure through the base of
the array.
[1434] In one embodiment, frozen piercing implements, including
microneedles, in an array define at last one cavity including at
least one therapeutic or other agent (e.g. a protein, nucleic acid,
cell, viral vector, or pharmaceutical). In one embodiment, both the
support structure and at least one frozen piercing implement, such
as a microneedle, define at least one cavity including at least one
therapeutic or other agent. In one embodiment, the support
structure includes at least one reservoir in fluid communication
with at least one frozen piercing implement, or other piercing
implement of the array that includes at least one frozen piercing
implement. In one embodiment, at least one frozen piercing
implement is hollow and is in fluid communication with at least one
external reservoir.
[1435] Cavitized or hollow frozen microneedles can be created by
laser drilling holes extending the length of the microneedles
projecting away from the support structure. See, for example,
Martanto et al, Ibid.
[1436] In one embodiment, the one or more frozen piercing
implements are utilized for delivery of at least one therapeutic
agent or other agent, diagnostic or detection materials or devices,
or sensing, or collecting one or more materials from the substrate
(e.g. blood, interstitial fluid, one or more cells or biological
materials). In one embodiment, at least one pump, syringe, or other
material transfer device is included in the frozen piercing
implement array. In one embodiment, a frozen piercing implement
array, such as a microneedle array, includes a manifold for
connection to a pump. See, for example, Martanto et al, Ibid.
[1437] In one embodiment, hollow frozen piercing implements, such
as microneedles, are utilized to deliver at least one therapeutic
or other agent in vivo. For example, McAllister et al, Proc. Natl.
Acad. Sci. USA, vol. 100, pp. 13755-13760 (2003), which is
incorporated herein by reference. As reported, hollow microneedles
interfaced with a pump providing 10-14 pounds/square inch of
pressure to deliver 32 .mu.l of insulin solution (100 units/ml
Humulin-R, Eli Lilly Co., Indianapolis, Ind.) to diabetic rats. As
reported, microneedle delivery of insulin is effective, as
indicated by the reduction in blood glucose levels in diabetic rats
following treatment. Id. As reported, microneedle injection
delivery of insulin is comparable in efficacy to subcutaneous
injection of insulin with a conventional hypodermic syringe
(McAllister et al, Ibid.).
[1438] Further, as reported, solid microneedles with tapered and
beveled tips and feature sizes from 1 to 1,000 .mu.m provide
increased skin permeability by orders of magnitude for
macromolecules and particles up to 50 nm in radius. Id.
[1439] In one embodiment, frozen hydrogen oxide microneedles are
coated with at least one therapeutic or other agent configured for
rapid release subsequent to piercing a substrate, such as skin. For
example, frozen piercing implements, such as microneedles, and the
corresponding arrays, are dip-coated by immersing them in stable
aqueous solutions of at least one therapeutic, adhesive, biological
remodeling, or other agent. For example, an agent such as
sulforhodamine (Invitrogen-Molecular Probes, Eugene, Oreg.),
FITC-labeled BSA ((Invitrogen-Molecular Probes, Eugene, Oreg.),
YOYO-3-labeled plasmid DNA (Invitrogen-Molecular Probes, Eugene,
Oreg.), sodium fluorescein (Sigma-Aldrich, St. Louis, Mo.), or
pilocarpine hydrochloride (Sigma-Aldrich, St. Louis, Mo.) are
dip-coated onto microneedles or other piercing implements. See, for
example, Jiang et al, Invest. Opthal. Vis. Sci., vol. 48, pp.
4038-4043 (2007), which is incorporated herein by reference.
[1440] In one embodiment, aqueous coating solutions containing
approximately 10% (wt/vol) polyvinylpyrrolidone (Sigma-Aldrich, St.
Louis, Mo.) and one or more therapeutic agents at concentrations
ranging from approximately 0.05% (wt/vol) to approximately 10%
(wt/vol) are coated on one or more frozen piercing implements, such
as microneedles. Id. As reported, microneedles coated with
approximately 280 ng of fluorescein or approximately 1.1 .mu.g of
pilocarpine, with dimensions of approximately 500 .mu.m in length,
approximately 100 .mu.m in width, and approximately 50 .mu.m in
thickness, are effective at delivering at least some of each agent
to the eye. Id.
[1441] In one embodiment, the strength of one or more frozen
piercing implements, such as microneedles, is measured by
subjecting the one or more frozen piercing implements to an axial
force (i.e. force parallel to the long dimension of the microneedle
(e.g., approximately 600 .mu.m) by using a displacement force test
station (Model 921 A, Tricor Systems, Elgin, IL). For example, a
stress versus strain curve is generated by measuring displacement
while the test station presses an array of microneedles or other
piercing implements against a rigid metal surface at a rate of
approximately 1.1 mm/sec.
[1442] As shown in FIG. 122, strength of microneedle or other
piercing implements is indicated by a sudden drop in force at the
point of failure. See, for example, Park et al., Ibid. The maximum
force just prior to the sudden drop defines the force of the
piercing implement failure. Piercing implements, including
microneedles, with failure forces greater than the force required
for penetration of the stratus corneum are suitable for transdermal
delivery. According to published studies, microneedles containing
polylactic acid with a height of approximately 800 .mu.m and a base
diameter of approximately 200 .mu.m display a failure force of
approximately 0.50 Newtons/needle, which is approximately three
times greater than the force needed for insertion into skin. See,
for example, Park et al, J. Contr. Rel., vol. 104, pp. 51-66
(2005), which is incorporated herein by reference.
[1443] In one embodiment, experimental data and theoretical models
are utilized to predict the failure force, or fracture force, of
piercing implements, including microneedles, which depends in part
on the implement geometry. See, for example, Davis et al, J.
Biomech., vol. 37, pp. 1155-1163 (2004) which is incorporated
herein by reference. For example, experiments to measure
microneedle fracture force can be done using an axial load test
station (Scope Test 1, EnduraTEC, Minnetonka, Minn.) to drive
microneedles against a flat block of aluminum at a rate of
approximately 0.01 mm/sec until a preset displacement of
approximately 500 .mu.m is reached. Id. Based on this test, force
and displacement data are used to determine the fracture force.
Id.
[1444] For example, microneedles or other piercing implements
approximately 500 .mu.m in length with: 1) variable tip radii and
constant wall thickness of approximately 12 .mu.m, and wall angle
of 78.5.degree.; or 2) variable wall thickness and constant tip
radius of approximately 43 .mu.m and wall angle of 78.5.degree.; or
3) variable wall angle and constant tip radius of approximately 30
.mu.m and wall thickness of approximately 10 .mu.m can be used to
measure fracture force variation with piercing implement geometry.
Id. As reported, the fracture force does not necessarily depend on
microneedle tip radius, but tends to increase with increasing wall
thickness and wall angle. Id. The geometry of any particular
piercing implement can be imaged by scanning electron microscopy,
for example, in order to determine at least the base radius, tip
radius, and wall thickness. Id. The interfacial area (i.e. the
effective area of contact between the needle and the skin) can be
calculated in at least two ways: (i) annular surface area, Aa, of
the piercing implement tip can be represented as
Aa=.pi.(r.sub.tt-t.sup.2/4) where r.sub.t=outer tip radius, and
t=wall thickness, or (ii) the full cross-sectional area, Af, at the
needle tip Af=.pi.r.sup.2.sub.t, while needle wall angle .alpha.,
can be calculated as .alpha.=tan.sup.-1[(r.sub.b-r.sub.t)/h], where
r.sub.t=outer tip radius, r.sub.b=outer radius at the needle base,
t is the wall thickness, and h is the height. Id.
[1445] Moreover, analytical models or finite element models can be
developed using standard techniques, and are capable of predicting
the fracture force of a microneedle, or other piercing implement,
with a given geometry. Id. As reported, both systems predict an
increase in fracture force with increase in wall thickness or wall
angle. Id. Accordingly, analytic or finite element models can be
developed for a particular frozen piercing implement, including a
microneedle, in such a way that the fracture force exceeds the
force required for administration to at least one substrate.
[1446] In one embodiment, the penetration of dermal layers or the
location of delivery of at least one agent is visualized by using
fluorescent molecules as tracers, followed by fluorescence
microscopy and bright field microscopy. For example, according to
published studies, delivery of sulforhodamine B (Molecular Probes,
Eugene, Oreg.) with microneedle arrays into pig cadaver skin is
assessed qualitatively by histological analysis, which includes
fluorescence microscopy, to establish the distribution of
sulforhodamine in the epidermis and dermis. See, for example, Lee
et al., Ibid.
[1447] In one embodiment, epidermis from cadaver skin sections are
placed in a diffusion chamber (Permegear, Hellertown, Pa.) and the
amount of sulforhodamine passing through the epidermis following
delivery with microneedle arrays is measured by spectrofluorimetry
(Lee et al, Ibid.). For example, in vivo delivery of agents, such
as therapeutic agents, adhesive agents, biological remodeling
agents, reinforcement agents, or other agents, by microneedle
arrays can be measured by evaluating local concentrations of the
agent, or plasma concentrations of the agent, i.e. pharmacokinetic
analysis.
[1448] In one embodiment, at least one agent is administered as a
component of the frozen piercing implement (or array). In one
embodiment, at least one agent is administered in conjunction with
the frozen piercing implement (or array), including sequentially,
serially, continuously, or other mode.
[1449] For example, delivery of naltrexone by a frozen piercing
implement array, such as a microneedle array, can be monitored by
analyzing plasma samples obtained at various time points following
administration. In one embodiment, plasma naltrexone concentrations
are determined by an assay, for example, employing high pressure
liquid chromatography and mass spectrometry.
[1450] For example, pharmacokinetic parameters for naltrexone (NTX)
(and its primary metabolite naltrexol (NTXOL)), following
permeation with a microneedle array and NTX delivery with a
transdermal patch are shown in Table C, adapted from Wermeling et
al, Proc. Natl. Acad. Sci. USA, vol. 105, pp. 2058-2063 (2008),
which is incorporated herein by reference. For example,
pharmacokinetic analysis includes calculation of partuclar values,
such as the steady state concentration (Css), the area under the
curve (AUC), and the time to reach steady state concentration
(Tlag), some of which can be done with computer programs. See, for
example, WinNonlin Professional, version 4.0; Pharsight, the
subject matter of which is incorporated herein by reference.
[1451] Additionally, the pharmacokinetic parameters obtained
following microneedle-enhanced transdermal delivery of NTX are
comparable to the pharmacokinetics obtained following oral
administration of NTX. See, for example, Wermeling et al, Ibid.
TABLE-US-00007 TABLE C NTX and NTXOL exposure after microneedle-
enhanced transdermal delivery Parameters NTX NTXOL Css, ng/ml 2.5
(1.0) 0.6 (0.5) Tlag, h 1.8 (1.1) 1.4 (1.4) Cmax, ng/ml 4.5 (2.4)
1.9 (1.3) Tmax, h 8.8 (7.6) 37.5 (31.3) AUC, ng h/ml 142.9 (43.9)
39.7 (25.9) Clast, ng/ml 1.8 (1.0) 0.4 (0.6) Results are expressed
as means .+-. SD (in parentheses) for six MN-treated subjects.
C.sub.ss = concentration at steady-state condition; T.sub.lag =
time to reach steady-state condition; C.sub.max = maximum
concentration achieved; T.sub.max = time to achieve maximum
concentration; AUC.sub.0-t = area under the concentration-time
curve from time 0 to 72 h; C.sub.last = concentration at time of
patch removal after 72 h of application.
[1452] As reported, pretreatment with microneedle arrays, removal
of the microneedles, and application of transdermal patches
containing NTX results in efficient delivery of NTX and achievement
of pharmacologically active blood concentrations of NTX (2.5 ng/ml)
within two hours after applying the patch. Id. The Css is
maintained for 48 hours. Id. Without microneedle pretreatment NTX
is not detected in the plasma following application of transdermal
patches. Id. Furthermore pretreatment of cadaver epidermis samples
with microneedle arrays followed by application of test drugs such
as calcein (Sigma Chemical Co., St. Louis, Mo.), or fluorescent BSA
(Texas Red conjugated-BSA, Molecular Probes, Eugene, Oreg.)
increases the skin permeability by more than 100-fold relative to
untreated epidermis. See, for example, Park et al, Ibid.
[1453] In one embodiment, frozen piercing implement arrays, or
microneedle arrays, are fabricated to include a support structure
that acts as a reservoir for sustained agent release. For example,
sustained release of at least one agent can occur even after
removal, sublimation, or melting of the frozen piercing implements,
and be delivered via microchannels created by the piercing
implement administration. For example, as published in Lee et al,
Ibid., an array of microneedles has a support structure that
contains a test drug, such as sulforhodamine. In one embodiment,
the frozen piercing implements, such as microneedles, include
sulforhodamine and an optional reinforcement agent, such as PLA. In
one embodiment, the base of the piercing implement contains frozen
sulforhodamine, buffers and water. Accordingly, frozen piercing
implements can be made that include channels, cavities, layers or
other areas.
[1454] In one embodiment, the tip of the frozen piercing implement
includes at least one constituent in common with the base of the
implement. In one embodiment, the tip of the frozen piercing
implement is different than the base of the implement. In one
embodiment, the support structure of the microarray is also frozen.
In one embodiment, the frozen piercing implement includes at least
one component that is not frozen. In one embodiment, the frozen
piercing implement array includes at least one implement that is
not frozen. In one embodiment, the frozen piercing implement array
includes at least one implement that is frozen.
[1455] In one embodiment, a large surface area is utilized for the
base of the piercing implement. For example, a piercing implement
with a base of approximately 81 mm.sup.2 and approximately 300
.mu.m thick, can accommodate milligram quantities of drug. See, for
example, Lee et al., Ibid. A relatively small piercing implement
array, such as a microneedle array, (for example, 7.times.7
implements) with a base composed of approximately 30% (wt %)
solution of sulforhodamine contains approximately 3 mg of
sulforhodamine. Administration of a piercing implement array with
amylopectin needles and base, and containing sulforhodamine,
results in sustained delivery of sulforhodamine across the
epidermis for about 12 hours. See, for example, Lee et al,
Ibid.
Example 28
Frozen Piercing Implements Utilized for Transdermal Delivery
[1456] In one embodiment, frozen piercing implements, such as
microneedles, include at least one non-aqueous constituent,
including but not limited to dimethyl sulfoxide, ethanol,
isopropanol, dimethyl formamide, or formaldehyde, as well as at
least one therapeutic agent. For example, using the methods
described in Lee et al, Ibid. micromolds can be constructed to
allow casting arrays of piercing implements derived from solutions
or suspensions of at least one agent in a non-aqueous solvent. For
example, in one embodiment, a therapeutic agent, such as a small
molecule (e.g. sulforhodamine (Molecular Probes, Eugene, Oreg.)), a
protein (e.g. bovine serum albumin (BSA) conjugated to Texas Red
(Molecular Probes, Eugene, Oreg.)), a nucleic acid (e.g.
gWiz.TM.luciferase plasmid DNA (6732 base pairs, Aldevron, Fargo,
ND, USA)), a viral particle (e.g. modified vaccinia virus--Ankara
(Emory University Vaccine Center, Atlanta, Ga., USA)) is suspended
or dissolved in dimethyl sulfoxide (DMSO) (freezing temperature is
approximately 18.5.degree. C. See, for example, Gill et al, J.
Control. Release, vol. 117, pp. 227-237 (2007), which is
incorporated herein by reference herein. In one embodiment, the
suspension or solution is cast in a piercing implement array mold
by using centrifugation. See, for example, Lee et al, Ibid. In one
embodiment, the piercing implements are frozen prior to, during, or
subsequent to centrifugation. Optionally, multiple layers can be
fabricated in the frozen piercing implements by repeating the
process of centrifuging/freezing and layering, then
centrifuging/freezing again.
[1457] In one embodiment, frozen piercing implement arrays, such as
microneedle arrays, with at least one frozen piercing implement
including, for example, DMSO and at least one agent, optionally
includes at least one reinforcement agent (e.g., a polymer, ceramic
particle (e.g. silica, alumina, hydroxyapatite), metal or fiber) to
increase the fracture strength of the frozen piercing
implements.
[1458] One example of a freezing method for a composite piercing
implement with increased fracture strength is described in Deville
et al, Science, vol. 311, pp. 515-518 (2006), which is incorporated
herein by reference. In one embodiment, frozen piercing implements,
including frozen microneedles, wherein at least one frozen piercing
implement includes DMSO, at least one reinforcement agent, such as
PLA, and at least one therapeutic agent, such as BSA. In one
embodiment, DMSO assists to disrupt the lipid bilayer of the
stratum corneum. Id. In one embodiment, other solvents or chemical
enhancers of skin permeability are utilized to increase efficiency
of administration of the at least one agent. See, for example,
Prausnitz et al, Nature Biotech., vol. 26, pp. 1261-1268 (2008),
which is incorporated herein by reference.
[1459] In one embodiment, frozen piercing implements, such as
frozen microneedles, include at least one frozen piercing implement
including DMSO, are utilized for delivery of viable mammalian
cells, with DMSO providing a cryoprotectant. For example, other
cryopreservatives for mammalian cells are available from
Sigma-Aldrich, St. Louis, Mo.
[1460] In one embodiment, frozen piercing implement arrays, or
frozen microneedle arrays, including at least one frozen piercing
implement that includes DMSO, is used for localized subcutaneous or
intradermal delivery of cytotoxic T cells to skin tumors for
treatment of metastatic melanoma or other skin disorders. See, for
example, Morgan et al, Science vol. 314, pp. 126-130 (2006), which
is incorporated herein by reference.
[1461] In one embodiment, frozen piercing implements, including
frozen microneedles, optionally include at least one abrasive or
explosive material. In one embodiment, the at least one abrasive or
explosive material provides additional capability for debriding
bone or other tissue, or abrading or ablating skin or other tissue.
In one embodiment, the at least one abrasive or explosive material
promotes transdermal delivery of at least one agent. For example,
frozen piercing implement arrays, such as frozen microneedle
arrays, include at least one frozen piercing implement including
carbon dioxide (CO.sub.2). In one embodiment, liquid CO.sub.2 can
be cast in microneedle molds maintained at approximately
-100.degree. C., the freezing temperature of CO.sub.2.
[1462] Some non-limiting examples of methods for measuring the
insertion force of microneedle arrays into human skin are described
by Davis et al, Ibid. In one embodiment, frozen piercing implements
including CO.sub.2 sublimate upon administration to the at least
one substrate. In one embodiment, the at least one substrate
includes skin.
[1463] In one embodiment, transdermal patches, including at least
one agent, is administered in conjunction with the frozen piercing
implement array, including the frozen microneedle array. In one
embodiment, pores or microchannels are created by frozen piercing
implements, which is amplified, for example, if the frozen piercing
implement includes at least one explosive material, such as carbon
dioxide. For example, the rapid sublimation of carbon dioxide
during administration of the frozen piercing implement array
results in a small "explosion" near the at least one substrate to
which the frozen piercing implement array is administered, which
can assist in delivery of at least one agent. For example, as
reported, transdermal delivery of naltrexone (a skin-impermeant
hydrophilic molecule) by transdermal patch remains undetected,
unless administered following administration of microneedles, when
pharmacologically active steady state levels of naltrexone are
detected. See, for example, Wermeling et al, Ibid.
Example 29
Frozen Piercing Implements, including Surgical Blades, Blade
Handles, and Scalpels
[1464] In one embodiment, at least one of a macroneedle (e.g.,
hypodermic needle), surgical blade, blade handle, scalpel, scalpel
blade, or other frozen cutting instrument (including detachable
blade and/or detachable blade handle) is fashioned by utilizing at
least one frozen composition (e.g., sterile hydrogen oxide, a
frozen solution including at least one fluid and at least one
agent, at least one frozen gas, or other frozen composition). In
one embodiment, the at least one fluid composition is frozen
according to methods described herein. In one embodiment, at least
one cutting instrument changes shape as it is used with at least
one substrate. In one embodiment, at least one cutting instrument
deposits at least one agent (such as a therapeutic agent,
biological remoding agent, adhesive agent, abrasive, explosive
material, or reinforcement agent) as it is used with at least one
substrate.
[1465] In one embodiment, the frozen composition includes sterile
hydrogen oxide including at least one agent, and is frozen at
approximately -196.degree. C., then raised to a temperature of
approximately -93.degree. C. to favor formation of ice Ic. See, for
example, Halbrucker et al, Ibid. In one embodiment, macroneedles,
surgical blades, or scalpels made from at least one frozen
composition, includes at least one reinforcement agents to increase
hardness and fracture strength. For example, glass fibers, silica
beads, alumina, calcium phosphate and calcium carbonate can be
added to hydrogen oxide to increase the hardness, modulus of
rupture and fracture force of frozen hydrogen oxide. See, for
example, Kingery et al, Ibid.; Kamrani et al, Ibid.; and Delville
et al, Science vol. 311, pp. 515-518 (2006), each of which is
incorporated herein by reference. In one embodiment, frozen cutting
instruments are coated with or include at least one therapeutic
agent. In one embodiment, the at least one therapeutic agent is
released into the substrate during use of the frozen cutting
instrument. In one embodiment, the substrate includes a surgical
site.
[1466] For example, in one embodiment, the frozen cutting
instrument is utilized in a procedure to transplant skin on burn
patients. In one embodiment, frozen surgical blades, or other
frozen cutting instruments, are coated with or otherwise include at
least one antibiotic. Some non-limiting examples include neomycin,
polymixin B, or gramicidin. In one embodiment, at least one other
agent, such as an adhesive agent or biological remodeling agent, is
included in the frozen cutting instrument. In one embodiment, the
at least one other agent includes at least one biological
remodeling agent, such as a growth factor, (e.g. keratinocyte
growth factor, vascular endothelial growth factor A, epidermal
growth factor, fibroblast growth factors and hepatocyte growth
factor) to promote the growth, vascularization or engraftment of
skin grafts, or avoid scarring or contraction of the graft(s). See,
for example, Nolte et al, Cells Tissue Organs, vol. 187, pp.
165-176 (2008); and Colwell et al, Plast. Reconstr. Surg., vol.
115, pp. 204-212 (2005), each of which is incorporated herein by
reference. Non-limiting examples of methods for coating frozen
cutting instruments are reported in Jiang et al, Ibid.
[1467] In one embodiment, frozen surgical blades are made in
lengths ranging from approximately 1-10 mm to approximately 10-50
mm. In one embodiment, the frozen surgical blades have at least one
surgical knife handle that includes at least one frozen
composition, such as hydrogen oxide, and an optional reinforcement
agent, such as metal filings or polymer fibers approximately 5 cm
to 13 cm long. Methods for casting handles of surgical knives using
two part molds are described in U.S. Pat. No. 4,846,250, which is
incorporated herein by reference.
[1468] In one embodiment, frozen surgical blades, or other frozen
cutting instruments, are made such that they terminate in at least
one of a point, rounded tip, jagged edge, serated edge, or other
configuration. In one embodiment, at least part of the length of
the entire cutting instrument includes a jagged or serated edge. In
one embodiment, at least one configuration includes one or more of
a single sharp edge, multiple sharp edges, or a continuous sharp
edge. In one embodiment, the frozen cutting instrument, such as a
frozen blade, includes at least one of a beveled edge, symmetric or
asymmetric double beveled edges, or curvilinear cutting edges. In
one embodiment, a smaller cutting edge radius is utilized, and
forms a sharper instrument.
[1469] In one embodiment, at least one abrasive or explosive
material is utilized in forming at least one surface of the cutting
instrument, in order to fabricate a rough surface.
[1470] In one embodiment, a surgical blade is made with cutting
edge radii that are approximately 5 nm to approximately 1000 nm.
See, for example, U.S. Pat. No. 6,386,952, which is incorporated
herein by reference. In one embodiment, the edges of a frozen
cutting instrument is sharpened by, for example, grinding,
mechanical abrasion, or lapping. Id. For example, various blade or
other cutting instrument profiles can be made, including but not
limited to single edge chisel, three edge chisel, slit, two edges
sharp, four edges sharp, stab, one edge sharp, keratome, one edge
sharp or crescent, curvilinear sharp edge, as well as others. See,
for example, U.S. Pat. No. 7,396,484, which is incorporated herein
by reference.
[1471] In one embodiment, frozen surgical blades or other cutting
instruments are made for specific purposes, such as opthalmic
surgery, arthroscopic, endoscopic, laparoscopic, diagnostic,
orthopedic, or plastic surgeries. See, for example, U.S. Pat. No.
6,547,802, which is incorporated herein by reference.
[1472] In one embodiment, frozen cutting instruments, such as
frozen surgical blades, are manufactured using methods that include
at least one of: machining trenches (or V-grooves) in wafers or
slabs of frozen compositions, or etching the trenches to produce
sharp cutting edges. For example, a frozen composition slab or
section can be secured on a mounting assembly and one or more
trenches (e.g. V-groove) can be machined with a router to create a
groove with any desired angle.
[1473] In one embodiment, trenches are made, for example, with a
dicing saw blade, laser system, ultrasonic machining tool, or a hot
forging process. See, for example, U.S. Pat. No. 7,396,484, Ibid.
In one embodiment, the machined frozen slab is etched with a laser
etching system to sublimate away layers of molecules from the
V-groove and to create a sharp cutting edge of uniform radius.
[1474] In one embodiment, etching is done with a laser etching
system that includes at least one of: a laser for producing a laser
beam (e.g. CO.sub.2 laser and an Er:YAG laser); a laser aiming
system adapted to aim and direct a laser beam onto the frozen slabs
(optionally including a lens to focus the laser beam and mirrors
coupled to drive devices such as servo-galvanometers); and has an
optional controller operatively coupled to the laser and laser
aiming system. See, for example, U.S. Patent Appl. Publ. No.
20080290065, which is incorporated herein by reference. In one
embodiment, the system includes a user interface such as a USB
port, a wireless network device, a CD-ROM drive or any combination
thereof, which is optionally coupled to the controller and allows
input of programmed designs or lines for etching the frozen
composition slabs. Id.
[1475] In one embodiment, one or more fluids are allowed to flow
over a cooled (including super cooled) surface (such as a metal
plate), where the fluid freezes. Prior to, during, or subsequent to
such freezing, the frozen composition can be etched, for example,
with a laser. As an optional next step, at least one agent or other
composition is allowed to flow over the frozen etched composition
(which may be in the form of frozen piercing implements, for
example), and optionally, the frozen composition is etched
again.
[1476] In one embodiment, one or more frozen surgical blades are
made by casting hydrogen oxide, or another fluid composition,
optionally with one or more reinforcements or one or more
therapeutic agents in a mold. As discussed herein at other
sections, molds for casting surgical blades are made by standard
techniques, such as for example, photolithography or molding
processes. For example, a first surgical blade mastermold is
created in SU-8 photoresist (SU-8 2025, Microchem, Newton, Mass.)
by UV exposure to create a surgical blade with a sharp point and
single cutting edge. In one embodiment, sharp point surgical blades
are formed with approximately 10 mm to approximately 50 mm in
length and approximately 4.65 mm to approximately 7.65 mm in width.
See, for example, U.S. Pat. No. 7,396,484, Ibid. and the worldwide
web at ribbil.com/fitting-dimensions.html, the content of each of
which is incorporated herein by reference.
[1477] In one embodiment, a second surgical blade master-structure
is made, for example, of polydimethylsiloxane (PDMS, Sylgard 184,
Dow Corning, Midland, Mich.) by using the first mastermold.
Additionally, multiple replicate molds are produced, for example,
by layering PDMS on the second master-structure. See, for example,
Lee et al, Biomaterials, vol. 29, pp. 2113-2124 (2008) which is
incorporated herein by reference. Finally, in one embodiment, fluid
hydrogen oxide, or another fluid composition, including at least
one reinforcement agent, such as silica, and including at least one
therapeutic agent, such as neomycin, is added to the molds and
frozen to create frozen piercing implements, such as frozen
surgical blades. In one embodiment, the cutting edge of the frozen
surgical blade can be sharpened by etching or by grinding to form
small edge radii, including approximately 5 nm to approximately
1000 nm. See, for example, U.S. Patent Appl. Publ. No. 20080290065,
Ibid.; U.S. Pat. No. 6,386,952, Ibid.; and U.S. Pat. No. 7,396,484,
Ibid., each of which is incorporated herein by reference.
[1478] In one embodiment, frozen surgical blades are die-cut,
coined or imprinted from slabs or sections of frozen hydrogen
oxide, or other frozen composition. For example, in one embodiment,
surgical blades are stamped from frozen hydrogen oxide, or other
frozen composition, by utilizing dies or stamping devices
configured to apply sufficient pressure to impress a negative image
of the die into the frozen composition. Some non-limiting examples
of imprinting methods are described, for example, in U.S. Pat. No.
7,105,103, which is incorporated herein by reference. Frozen
surgical blades manufactured by die-cutting or imprinting can be
sharpened using grinding, lapping, or etching. See, for example,
U.S. Patent Appl. Pub. No. 20080290065, Ibid.; U.S. Pat. No.
6,386,952, Ibid.; and U.S. Pat. No. 7,396,484, Ibid., each of which
is incorporated herein by reference.
[1479] In one embodiment, the frozen cutting instrument (such as a
blade) is sharpened, for example, by using cylindrical abrasive
wheels interlocked to form a nip. In one embodiment, the cutting
instrument is sharpened, for example, by utilizing grinding
assemblies mounted for rotation about parallel axes. See, for
example, U.S. Pat. No. 6,386,952, Ibid.
Example 30A
Method of Making Frozen Particle Compositions or Frozen Piercing
Implements
[1480] Frozen particle compositions, including at least one frozen
or deposited fluid, are produced from small droplets in a nonlinear
channel including at least one super hydrophobic surface. For
example, at least one fluid is sprayed as droplets, a mist, etc.
into a nonlinear channel maintained at low temperature (e.g.,
approximately -100.degree. C.), or high pressure (e.g.,
approximately 2000 bar). For example, at 2100 bar, hydrogen oxide
is 1500 times more viscous than at atmospheric pressure, which
reduces the nucleation and crystal growth rate. See, for example,
product guide for HPM 010 High Pressure Freezing Machine, available
at the worldwide web at: rmcproducts.com, the subject matter of
which is incorporated herein by reference. Droplet size is
regulated by varying nozzle or aperture size, and pressure. Fluid
droplet diameters range, for example, from nanometers to
centimeters. In one embodiment, the fluid droplets freeze or
deposit along the nonlinear channel, forming frozen particle
compositions.
[1481] In one embodiment, the frozen fluid particle compositions
are translocated to at least one compartment that contains at least
one cooling fluid with a triple point lower than the triple point
of the frozen fluid particle compositions, such that the frozen
fluid compositions are retained in solid form. In one embodiment,
the fluid droplets are translocated along the nonlinear channel,
where at least one other fluid or at least one agent is added by
way of at least one inlet. In one embodiment, the fluid
compositions are translocated to at least one compartment, wherein
they combine to form frozen particle compositions.
[1482] In one embodiment, the fluid compositions are cycled through
multiple stages of freezing or deposition, in order to layer
multiple fluids or agents, or in order to attain a particular state
(e.g., crystalline state). In one embodiment, fluid compositions
are subjected to conditions in the nonlinear channel that favor
crystalline states, thereby forming at least one frozen piercing
implement.
[1483] In one embodiment, the cooling fluid includes at least one
refrigerant or cryogenic fluid. In one embodiment, the cooling
fluid includes at least one fluid included in the frozen particle
composition or frozen piercing implement.
Example 30B
Method of Propelling or Administering Frozen Particle Compositions
or Frozen Piercing Implements
[1484] At least one frozen particle composition or frozen piercing
implement is received or retained in at least one compartment
containing one or more cooling fluids. In one embodiment, the at
least one frozen particle composition or frozen piercing implement
is formed prior to being received in the at least one compartment.
In one embodiment, the at least one frozen particle composition or
frozen piercing implement is formed by way of extrudation,
embossing, cutting, splintering, etching, molding, electrospinning,
electrospraying, gel-casting, spin-casting, or other method, and
subsequently translocated to at least one compartment.
[1485] In one embodiment, the at least one frozen particle
composition or frozen piercing implement is formed while residing
in the at least one compartment.
[1486] In one embodiment, the cooling fluid includes at least one
refrigerant or cryogenic fluid. In one embodiment, the cooling
fluid includes at least one fluid included in the frozen particle
composition or frozen piercing implement.
[1487] In one embodiment, the cooling fluid includes at least one
cooling liquid. In one embodiment, the frozen particle compositions
or frozen piercing implements are propelled out of the compartment
(e.g., by way of at least one outlet) by inducing at least one
explosion in the cooling fluid. In one embodiment, the explosion
includes flash-boiling the at least one cooling liquid. In one
embodiment, the explosion includes a boiling liquid expanding vapor
explosion (BLEVE) of the at least one cooling liquid.
[1488] The BLEVE of the cooling liquid can be calculated according
to standard techniques. For example, in FIG. 119, a diagram of the
relationship between the pressure for a substance in various phases
of liquid and gas, and the volume occupied by that substance. See,
for example, the worldwide web at: criticalprocesses.com/BLEVE.htm,
the subject matter of which is incorporated herein by reference.
The line from point A to B indicates the substance is in liquid
form and as the volume the substance occupies expands, the pressure
falls until it reaches the vapor pressure of the liquid (B) for a
particular temperature. Id. The liquid then evaporates to become a
liquid-gas mixture, and the pressure stays constant at the vapor
pressure. Eventually the substance reaches point C, where the
liquid has been converted to gas phase, and the pressure drops with
further expansion. Id. If the pressure falls suddenly, the
substance can become unstable liquid along the line from point B to
point S. Id. S is known as a spinodal point, and the slope of the
line at this point is zero (i.e. (.alpha.p/.alpha.V)=0). Id. The
dotted line connects spinodal points at different temperatures,
forming the spinodal curve, and ending at the critical point. Id.
During a BLEVE, density variations develop spontaneously and
homogenously into liquid and gas regions. Id. The rise in pressure
on the vapor pressure line from point B to C occurs rapidly, and a
BLEVE results. Id. As illustrated in FIG. 120, for carbon dioxide,
conditions for inducing a BLEVE can be calculated for a particular
substance since the entropy of the system remains constant. Id.
Thus, conditions that induce a BLEVE for any particular substance
are found along the spinodal curve for that substance, between 1
bar and the critical point where the curve ends. Id.
[1489] In one embodiment, the cooling fluid is flash boiled. In one
embodiment, the cooling fluid is a liquid. As with all liquids,
vapor pressure increases with temperature approximately
exponentially. For example, the boiling point of nitrogen at 1 bar
is approximately 77 K (-196.degree. C.), whereas the boiling point
of nitrogen at 10 bar is approximately 103.8 K (-169.2.degree. C.).
Accordingly, pressure can be used to control reaction temperature,
and controlling pressure above a cryogenic bath, for example, via
regulators and pumps can maintain accurate temperature control.
See, for example, Downie, Industrial Gases, pp. 445-446, Blackie
Academic and Prof. (1996).
[1490] In one embodiment, the size of the outlet assists in
dispersion by altering spray cone angles, altering particle size,
altering depressurization rates, and altering mass flow rates. See,
for example, Nutter, J. Energy Res. Technol. vol. 119, no. 3
(1997), which is incorporated herein by reference.
[1491] In one embodiment, the frozen particle compositions or
frozen piercing implements are directionally propelled for
administration to at least one substrate. For example, a handheld
device, or a hose and nozzle system can be used, with or without a
carrier gas, (e.g., air or nitrogen) under pressure, to administer
the frozen particle compositions or frozen piercing implements to
at least one substrate.
[1492] In one embodiment, the substrate includes at least one cell,
tissue, organ, structure, or device. In one embodiment, the
substrate includes at least one food product (e.g., fruit juice,
cereals, grains, sugar, soda, meat, vegetables, canned goods, baked
goods, fruits, etc.). In one embodiment, the substrate includes at
least part of a subject.
[1493] While particular aspects of the present subject matter
described herein have been shown and described, it will be apparent
to those skilled in the art that, based upon the teachings herein,
changes and modifications can be made without departing from the
subject matter described herein and its broader aspects and,
therefore, the appended claims are to encompass within their scope
all such changes and modifications as are within the true spirit
and scope of the subject matter described herein. It will be
understood by those within the art that, in general, terms used
herein, and especially in the appended claims (e.g., bodies of the
appended claims) are generally intended as "open" terms (e.g., the
term "including" should be interpreted as "including but not
limited to," the term "having" should be interpreted as "having at
least," the term "includes" should be interpreted as "includes but
is not limited to," etc.). It will be further understood by those
within the art that if a specific number of an introduced claim
recitation is intended, such an intent will be explicitly recited
in the claim, and in the absence of such recitation no such intent
is present. For example, as an aid to understanding, the following
appended claims may contain usage of the introductory phrases "at
least one" and "one or more" to introduce claim recitations.
However, the use of such phrases should not be construed to imply
that the introduction of a claim recitation by the indefinite
articles "a" or "an" limits any particular claim containing such
introduced claim recitation to claims containing only one such
recitation, even when the same claim includes the introductory
phrases "one or more" or "at least one" and indefinite articles
such as "a" or "an" (e.g., "a" and/or "an" should typically be
interpreted to mean "at least one" or "one or more"); the same
holds true for the use of definite articles used to introduce claim
recitations. In addition, even if a specific number of an
introduced claim recitation is explicitly recited, those skilled in
the art will recognize that such recitation should typically be
interpreted to mean at least the recited number (e.g., the bare
recitation of "two recitations," without other modifiers, typically
means at least two recitations, or two or more recitations).
Furthermore, in those instances where a convention analogous to "at
least one of A, B, and C, etc." is used, in general such a
construction is intended in the sense one having skill in the art
would understand the convention (e.g., "a system having at least
one of A, B, and C" would include but not be limited to systems
that have A alone, B alone, C alone, A and B together, A and C
together, B and C together, and/or A, B, and C together, etc.). In
those instances where a convention analogous to "at least one of A,
B, or C, etc." is used, in general such a construction is intended
in the sense one having skill in the art would understand the
convention (e.g., "a system having at least one of A, B, or C"
would include but not be limited to systems that have A alone, B
alone, C alone, A and B together, A and C together, B and C
together, and/or A, B, and C together, etc.). It will be further
understood by those within the art that typically a disjunctive
word and/or phrase presenting two or more alternative terms,
whether in the description, claims, or drawings, should be
understood to contemplate the possibilities of including one of the
terms, either of the terms, or both terms unless context dictates
otherwise. For example, the phrase "A or B" will be typically
understood to include the possibilities of "A" or "B" or "A and
B."
[1494] With respect to the appended claims, those skilled in the
art will appreciate that recited operations therein may generally
be performed in any order. Also, although various operational flows
are presented in a sequence(s), it should be understood that the
various operations can be performed in other orders than those
which are illustrated, or can be performed concurrently. Examples
of such alternate orderings may include overlapping, interleaved,
interrupted, reordered, incremental, preparatory, supplemental,
simultaneous, reverse, or other variant orderings, unless context
dictates otherwise. Furthermore, terms like "responsive to,"
"related to," or other past-tense adjectives are generally not
intended to exclude such variants, unless context dictates
otherwise.
[1495] All publications and patent applications cited in this
specification are incorporated herein by reference to the extent
not inconsistent with the description herein and for all purposes
as if each individual publication or patent application were
specifically and individually indicated to be incorporated by
reference for all purposes.
* * * * *
References