U.S. patent application number 14/591824 was filed with the patent office on 2015-06-11 for autofluorescent imaging and target ablation.
The applicant listed for this patent is Searete LLC. Invention is credited to Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Eric C. Leuthardt, Nathan P. Myhrvold, Dennis J. Rivet, Thomas Allan Weaver, Lowell L. Wood, JR..
Application Number | 20150157877 14/591824 |
Document ID | / |
Family ID | 39152715 |
Filed Date | 2015-06-11 |
United States Patent
Application |
20150157877 |
Kind Code |
A1 |
Boyden; Edward S. ; et
al. |
June 11, 2015 |
AUTOFLUORESCENT IMAGING AND TARGET ABLATION
Abstract
Apparatus, devices, methods, systems, computer programs and
computing devices related to autofluorescent imaging and ablation
are disclosed.
Inventors: |
Boyden; Edward S.; (Chestnut
Hill, MA) ; Hyde; Roderick A.; (Redmond, WA) ;
Ishikawa; Muriel Y.; (Livermore, CA) ; Leuthardt;
Eric C.; (St. Louis, MO) ; Myhrvold; Nathan P.;
(Bellevue, WA) ; Rivet; Dennis J.; (Chesapeake,
VA) ; Wood, JR.; Lowell L.; (Bellevue, WA) ;
Weaver; Thomas Allan; (San Mateo, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Searete LLC |
Bellevue |
WA |
US |
|
|
Family ID: |
39152715 |
Appl. No.: |
14/591824 |
Filed: |
January 7, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11901299 |
Aug 24, 2007 |
8936629 |
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14591824 |
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|
11645357 |
Dec 21, 2006 |
7857767 |
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11901299 |
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|
11403230 |
Apr 12, 2006 |
9011329 |
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11645357 |
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Current U.S.
Class: |
607/92 |
Current CPC
Class: |
A61B 5/07 20130101; A61N
5/0603 20130101; A61B 5/0088 20130101; A61B 18/20 20130101; A61B
5/4547 20130101; A61B 5/0084 20130101; A61N 5/10 20130101; A61N
5/0624 20130101; A61B 5/0071 20130101; A61B 5/0086 20130101; A61N
2005/0663 20130101; A61B 5/0091 20130101; A61N 2005/0626 20130101;
A61N 5/01 20130101; A61B 5/412 20130101 |
International
Class: |
A61N 5/06 20060101
A61N005/06; A61N 5/01 20060101 A61N005/01 |
Claims
1. A device for treating or ameliorating H. pylori infection, the
device comprising: an untethered ingestible mass having, one or
more sensor coupled to control circuitry, the one or more sensors
configured to detect one or more environmental parameters; and one
or more optical energy source configured to emit variable
directional electromagnetic energy in a manner selected to induce
photodynamic cell death in H. pylori responsive to the one or more
sensor detecting the one or more environmental parameters.
2-5. (canceled)
6. The device of claim 1, wherein the untethered ingestible mass is
a rotationally symmetrical body with an axial dimension greater
than an equatorial dimension.
7. The device of claim 1, wherein the untethered ingestible mass is
spherical.
8-11. (canceled)
12. The device of claim 1, wherein the untethered ingestible mass
is designed to randomly wobble.
13. The device of claim 1, further comprising: a motor coupled to a
movable mass.
14. The device of claim 13, wherein the movable mass is configured
to vary the moment of inertia of the untethered ingestible
mass.
15. The device of claim 14, wherein the movable mass is configured
to undergo unbalanced rotation.
16. The device of claim 13, wherein the movable mass is configured
to undergo linear oscillatory motion.
17. The device of claim 13, wherein the movable mass is configured
to undergo eccentric motion.
18. The device of claim 13, further comprising: a power source
including one or more of a battery, a capacitor, or a wireless
power source.
19-30. (canceled)
31. The device of claim 18, wherein the control circuitry is
wirelessly coupled to the power source.
32. The device of claim 1, wherein the control circuitry is
remote-controlled.
33. The device of claim 1, wherein the control circuitry is
programmed.
34. The device of claim 1, wherein the control circuitry is
configured to be monitored by one or more external sources.
35. The device of claim 1, wherein the control circuitry is
configured to provide one or more outputs to one or more external
sources.
36-37. (canceled)
38. The device of claim 1, wherein the one or more environmental
parameters include one or more of pH or orientation of the
untethered ingestible mass.
39-44. (canceled)
45. The device of claim 1, wherein the electromagnetic energy has a
wavelength of approximately 408 nm.
46. (canceled)
47. The device of claim 1, wherein the one or more optical energy
source is configured to emit the electromagnetic energy in multiple
directions.
48-52. (canceled)
53. The device of claim 1, wherein the one or more optical energy
source is configured emit the electromagnetic energy in a
pH-dependent manner.
54-129. (canceled)
130. A untethered device for inducing photodynamic death in a
pathogen or a pathological tissue, the device comprising: an
untethered substantially spherical mass including, a first optical
energy source configured to emit a first electromagnetic energy
that is selected to induce an auto-fluorescent response in at least
some of the pathogen or the pathological tissue; a sensor
configured to detect the auto-fluorescent response; control
circuitry coupled to the sensor and configured to identify at least
one target of the at least some of the pathogen or the pathological
tissue by analyzing the auto-fluorescent response; and a second
energy source configured to emit a second electromagnetic energy
that is selected to induce photodynamic death in the at least one
target responsive to the control circuitry identifying the at least
one target.
131. The untethered device of claim 130 wherein the untethered
substantially spherical mass includes: one or more controllable
arms connected to and extending from an outer surface of the
untethered substantially spherical mass; and one or more paddles
connected to corresponding ones of the one or more arms.
132. The untethered device of claim 131 wherein the untethered
substantially spherical mass is configured to randomly rotate based
on motion of the one or more arms.
133. The untethered device of claim 131 wherein at least some of
the one or more paddles have different orientations from each
other.
134. The untethered device of claim 130 wherein the untethered
substantially spherical mass includes an outer surface that is
covered with multiple openings.
135. The untethered device of claim 134 wherein the first optical
energy source is configured to emit the first electromagnetic
energy in multiple directions through the multiple openings in the
outer surface of the untethered substantially spherical mass.
136. The untethered device of claim 134 wherein the induced
autoflorescence is detected through multiple openings in the outer
surface of the untethered substantially spherical mass.
137. The untethered device of claim 134 wherein the second optical
energy source is configured to emit the second electromagnetic
energy in multiple directions through the multiple openings in the
outer surface of the untethered substantially spherical mass.
138. The untethered device of claim 134 wherein the multiple
openings are spaced from one another and cover the substantially
entire outer surface of the untethered substantially spherical
mass.
139. The untethered device of claim 134, wherein the multiple
openings are positioned on the outer surface to emit the first
electromagnetic energy from the first optical energy source and the
second electromagnetic energy from the second energy source
radiating in all directions from the untethered substantially
spherical mass.
140. The untethered device of claim 139, wherein the multiple
openings are positioned on the outer surface to detect at the
sensors the auto-fluorescence received from all directions at the
untethered substantially spherical mass.
141. The untethered device of claim 130 wherein the pathogen
includes H. pylori.
142. The untethered device of claim 130 wherein the untethered
substantially spherical mass includes a central core configured to
pass the pathogen or pathological tissue therethrough.
143. The untethered device of claim 142 wherein the second
electromagnetic energy is selected to induce photodynamic death of
the pathogen or pathological tissue passing through the central
core of the untethered substantially spherical mass.
144. A untethered device for inducing photodynamic death in a
pathogen or a pathological tissue, the device comprising: an
untethered substantially spherical mass including an outer surface
covered with multiple openings, the untethered substantially
spherical mass including, a first optical energy source configured
to emit a first electromagnetic energy in multiple directions
through the multiple openings, the first electromagnetic energy
selected to induce an auto-fluorescent response in at least some of
the pathogen or the pathological tissue; a sensor configured to
detect the auto-fluorescent through the multiple openings in the
outer surface; control circuitry coupled to the sensor and
configured to identify at least one target of the at least some of
the pathogen or the pathological tissue by analyzing the
auto-fluorescent response; and a second energy source configured to
emit a second electromagnetic energy in multiple directions through
the multiple openings, the second electromagnetic energy selected
to induce photodynamic death in the at least one target responsive
to the control circuitry identifying the at least one target.
145. The untethered device of claim 144, wherein the multiple
openings are positioned on the outer surface to emit the first
electromagnetic energy from the first optical energy source and the
second electromagnetic energy from the second energy source
radiating in all directions from the untethered substantially
spherical mass.
146. The untethered device of claim 145, wherein the multiple
openings are positioned on the outer surface to detect at the
sensors the auto-fluorescence received from all directions at the
untethered substantially spherical mass.
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)).
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. 11/403,230, entitled LUMENALLY-ACTIVE
DEVICE, naming Bran Ferren; W. Daniel Hillis; Roderick A. Hyde;
Muriel Y Ishikawa; Edward K. Y. Jung; Nathan P. Myhrvold; Elizabeth
A. Sweeney; Clarence T. Tegreene; Richa Wilson; Lowell L. Wood, Jr.
and Victoria Y. H. Wood as inventors, filed 12 Apr. 2006, 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.
11/645,357, entitled LUMENALLY-TRAVELING DEVICE, naming Bran
Ferren; W. Daniel Hillis; Roderick A. Hyde; Muriel Y Ishikawa;
Edward K. Y. Jung; Eric C. Leuthardt; Nathan P. Myhrvold; Elizabeth
A. Sweeney; Clarence T. Tegreene; Richa Wilson; Lowell L. Wood, Jr.
and Victoria Y. H. Wood as inventors, filed 21 Dec. 2006, 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. ______,
entitled AUTOFLUORESCENT IMAGING AND TARGET ABLATION, naming Edward
S. Boyden; Roderick A. Hyde; Muriel Y. Ishikawa; Eric C. Leuthardt;
Nathan P. Myhrvold; Dennis J. Rivet; and Lowell L. Wood, Jr. as
inventors, filed 24 Aug. 2007, 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. [Attorney Docket No.
0606-002-012A-000000] [0005] For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No. ______,
entitled SYSTEMS FOR AUTOFLUORESCENT IMAGING AND TARGET ABLATION,
naming Edward S. Boyden; Roderick A. Hyde; Muriel Y. Ishikawa; Eric
C. Leuthardt; Nathan P. Myhrvold; Dennis J. Rivet; and Lowell L.
Wood, Jr. as inventors, filed 24 Aug. 2007, 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.
[Attorney Docket No. 0606-002-012B-000000] [0006] For purposes of
the USPTO extra-statutory requirements, the present application
constitutes a continuation-in-part of U.S. patent application Ser.
No. ______, entitled SYSTEMS FOR AUTOFLUORESCENT IMAGING AND TARGET
ABLATION, naming Edward S. Boyden; Roderick A. Hyde; Muriel Y.
Ishikawa; Eric C. Leuthardt; Nathan P. Myhrvold; Dennis J. Rivet;
and Lowell L. Wood, Jr. as inventors, filed 24 Aug. 2007, 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. [Attorney Docket No. 0606-002-012C-000000] [0007] For
purposes of the USPTO extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. ______, entitled AUTOFLUORESCENT IMAGING AND
TARGET ABLATION, naming Edward S. Boyden; Roderick A. Hyde; Muriel
Y. Ishikawa; Eric C. Leuthardt; Nathan P. Myhrvold; Dennis J.
Rivet; and Lowell L. Wood, Jr. as inventors, filed 24 Aug. 2007,
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. [Attorney Docket No. 0606-002-012D-000000] [0008] For
purposes of the USPTO extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. ______, entitled SYSTEM FOR AUTOFLUORESCENT
IMAGING AND TARGET ABLATION, naming Edward S. Boyden; Roderick A.
Hyde; Muriel Y. Ishikawa; Eric C. Leuthardt; Nathan P. Myhrvold;
Dennis J. Rivet; and Lowell L. Wood, Jr. as inventors, filed 24
Aug. 2007, 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. [Attorney Docket No. 0606-002-012E-000000]
[0009] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. ______, entitled AUTOFLUORESCENT
IMAGING AND TARGET ABLATION, naming Edward S. Boyden; Roderick A.
Hyde; Muriel Y. Ishikawa; Eric C. Leuthardt; Nathan P. Myhrvold;
Dennis J. Rivet; and Lowell L. Wood, Jr. as inventors, filed 24
Aug. 2007, 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. [Attorney Docket No. 0606-002-012G-000000]
[0010] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. ______, entitled AUTOFLUORESCENT
IMAGING AND TARGET ABLATION, naming Edward S. Boyden; Roderick A.
Hyde; Muriel Y. Ishikawa; Eric C. Leuthardt; Nathan P. Myhrvold;
Dennis J. Rivet; and Lowell L. Wood, Jr. as inventors, filed 24
Aug. 2007, 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. [Attorney Docket No. 0606-002-012H-000000]
[0011] The U.S. 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).
[0012] 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.
SUMMARY
[0013] The present application relates, in general, to apparatus
and devices for fluorescent-based imaging and ablation of medical
targets, as well as related methods and systems implementations.
Such apparatus, devices, methods and/or systems are useful for
ablating target cells and/or tissues as well as treatment,
prevention, and/or amelioration of a variety of diseases and
disorders. Apparatus and/or devices may be configured to be used
externally or internally, to be handheld, intra-luminal, or
ingestible, and/or to be tethered or untethered. Various methods
and/or systems implementations include using one or more of the
apparatus or devices for ablating target cells in wounds and/or
surgical lesions, intra-lumenally, or in the digestive tract.
Illustrative examples include using one or more of the apparatus,
devices, methods and/or systems to treat H. pylori infection,
and/or to test and ablate cancer margins.
[0014] The foregoing summary is illustrative only and is not
intended to be in any way limiting. In addition to the illustrative
aspects, embodiments, and features described above, further
aspects, embodiments, and features will become apparent by
reference to the drawings and the following detailed
description.
BRIEF DESCRIPTION OF THE FIGURES
[0015] FIG. 1 shows a schematic of an illustrative apparatus in
which embodiments may be implemented.
[0016] FIG. 2 shows a schematic of illustrative embodiments of the
apparatus of FIG. 1, with illustrative examples of an energy
source.
[0017] FIG. 3 shows a schematic of illustrative embodiments of the
apparatus of FIG. 1, with illustrative examples of a sensor.
[0018] FIGS. 4-6 show a schematic of an illustrative untethered
device in which embodiments may be implemented.
[0019] FIG. 7 shows a schematic of an illustrative tethered device
in which embodiments may be implemented.
[0020] FIG. 8 and FIG. 9 show an operational flow representing
illustrative embodiments of operations related to providing a first
output to a first energy source in real time, the first output
providing data associated with at least partial ablation of a
target at least partially based on the first possible dataset.
[0021] FIG. 10 and FIG. 11 show an operational flow representing
illustrative embodiments of operations related to providing a first
output to a first energy source in real time, the first output
providing data representative of one or more ablation
characteristics for at least partially ablating a target area.
[0022] FIG. 12 and FIG. 13 show an operational flow representing
illustrative embodiments of operations related to providing a first
possible output to a first motive source, the first possible output
providing data representative of one or more parameters associated
with movement of an untethered device in a lumen at least partially
based on the location of the target area.
[0023] FIGS. 14-19 show a partial view of an illustrative
embodiment of a computer program product that includes a computer
program for executing a computer process on a computing device.
[0024] FIGS. 20-25 show an illustrative embodiment of a system in
which embodiments may be implemented.
[0025] FIG. 26 shows a schematic of an example of an illustrative
embodiment of a handheld device in use on an illustrative
subject.
[0026] FIG. 27 shows a schematic of an example of an illustrative
embodiment of a device in use on an illustrative subject.
[0027] FIG. 28 shows a schematic of an example of an illustrative
embodiment of a handheld device in use on an illustrative
subject.
[0028] FIG. 29 shows a schematic of an example of an illustrative
embodiment of a device in use on an illustrative subject.
[0029] FIGS. 30-31 show a schematic of an example of an
illustrative embodiment of a handheld device.
[0030] FIGS. 32A, 32B, and 32C show a schematic of an example of an
illustrative embodiment of a handheld device.
[0031] FIG. 33 shows a schematic of an example of an illustrative
embodiment of an untethered device in use on an illustrative
subject.
[0032] FIGS. 34-40 show a schematic of an example of an
illustrative embodiment of an untethered device in use on an
illustrative subject.
DETAILED DESCRIPTION
[0033] 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 may be utilized, and other
changes may be made, without departing from the spirit or scope of
the subject matter presented here.
[0034] The present application relates, in general, to apparatus,
devices, systems, and methods of fluorescent imaging, optionally
autofluorescent imaging, and ablation of medical targets. Those
having skill in the art will appreciate that the specific systems,
apparatus, devices, and methods described herein are intended as
merely illustrative of their more general counterparts.
[0035] In one aspect, FIG. 1 through FIG. 7 depict one or more
embodiments of one or more apparatus 100 and/or 500 and/or devices
200, 300, and/or 400 configured to detect and ablate targets at
least partially based on a fluorescent response. Although one or
more embodiments of one or more apparatus and/or devices may be
presented separately herein, it is intended and envisioned that one
or more apparatus and/or devices and/or embodiments of one or more
apparatus and/or devices, in whole or in part, may be combined
and/or substituted to encompass a full disclosure of the one or
more apparatus and/or devices. In some embodiments, one or more
apparatus and/or devices may include one or more system
implementations including methods of operations, and/or include one
or more computing devices and/or systems configured to perform one
or more methods. As disclosed below, one or more apparatus and/or
devices may be used in one or more methods of treatment and/or
methods for ablating targets described herein.
[0036] FIG. 1, FIG. 2, and FIG. 3 depict illustrative embodiments
of one or more apparatus 100 having a first energy source 110
alignable to a lesion and configured to provide electromagnetic
energy selected to induce a fluorescent response from a target area
in the lesion; a sensor 120 configured to detect the fluorescent
response; control circuitry 130 coupled to the sensor 120 and
responsive to identify the target area; and a second energy source
110 responsive to the control circuitry 130 and configured to emit
energy selected to at least partially ablate the target area.
[0037] FIG. 4, FIG. 5, and FIG. 6 depict illustrative embodiments
of one or more untethered device 200, 300, and 400,
respectively.
[0038] FIG. 4 depicts illustrative embodiments of one or more
untethered device 200 having an energy source 100, optionally a
first electromagnetic energy source 111 configured to function in a
lumen and configured to provide electromagnetic energy selected to
induce an auto-fluorescent response in one or more target cells in
proximity to the lumen; a sensor 120 configured to detect the
auto-fluorescent response; control circuitry 130 coupled to the
sensor 120 and responsive to identify a target area; optionally a
second electromagnetic energy source 111 responsive to the control
circuitry 130 and configured to emit energy selected to at least
partially ablate the target area, optionally a power source 140,
and optionally a motive source 150.
[0039] FIG. 5 depicts illustrative embodiments of one or more
devices 300 for treating or ameliorating H. pylori infection
including an untethered ingestible mass 310 optionally shaped for
non-uniform movement having an electromagnetic energy source 111
optionally configured to emit variable directional electromagnetic
energy in a manner selected to induce photodynamic cell death in H.
pylori. In some embodiments, one or more devices 300 for ablating
H. pylori include an untethered ingestible mass 310, optionally
shaped for non-uniform movement, having an electromagnetic energy
source 111 optionally configured to emit variable directional
electromagnetic energy in a manner selected to induce photodynamic
cell death in H. pylori.
[0040] FIG. 6 depicts illustrative embodiments of one or more
devices 400 including an untethered ingestible mass 310 optionally
configured to rotate, optionally shaped for non-uniform movement,
wherein the untethered ingestible mass 310 includes: an energy
source 110, optionally a first electromagnetic energy source 111
configured to provide electromagnetic energy selected to stimulate
an auto-fluorescent response in one or more target cells in a
digestive tract; a sensor 120 configured to detect the
auto-fluorescent response; control circuitry 130 coupled to the
sensor 120 and responsive to identify a target area; optionally a
second electromagnetic energy source 111 responsive to the control
circuitry 130 and configured to emit energy selected to at least
partially ablate the target area, optionally a power source 140,
and optionally a motive source 150.
[0041] FIG. 7 depicts illustrative embodiments of one or more
tethered 510 apparatus 500 including a first energy source 110
configured to provide electromagnetic energy selected to stimulate
an auto-fluorescent response in one or more target cells in an
internal location; a sensor 120 configured to detect the
auto-fluorescent response; control circuitry 130 coupled to the
sensor 120 and responsive to identify a target area in real time;
and optionally a second energy source 110 responsive to the control
circuitry 130 and configured to emit energy selected to at least
partially ablate the target area.
[0042] Embodiments of one or more apparatus 100 and/or 500 and/or
devices 200, 300, and/or 400 may be configured for use in one or
more lesions, lumens, and/or internal locations of an organism. In
illustrative embodiments, one or more apparatus 100, in part or in
whole, is optionally a handheld device configured for detecting and
ablating microbial and/or pathological contamination or cancer
cells, for example, in lesions, optionally wounds or surgical
incisions. In illustrative embodiments, one or more devices 200, in
part or in whole, is an intra-lumenally sized device (e.g. small
enough to be placed in a blood vessel while not obstructing the
flow) configured for detecting and ablating microbial and/or
pathogenic infections or cancer cells/metastases, for example, in
the blood steam. In illustrative embodiments, one or more devices
300 and/or 400, in whole or in part, is an ingestibly-sized device
(e.g. the size of a large vitamin pill) configured for detecting
and ablating microbial and/or pathogenic infections or cancer
cells, for example, in the digestive tract. In illustrative
embodiments, one or more apparatus 500, in whole or in part, is
part of or attached to a device, optionally handheld (e.g. an
endoscope or fiber optic cable) and configured for detecting and
ablating microbial and/or pathogenic infections or cancer cells,
for example, in internal locations.
[0043] Embodiments of one or more apparatus 100 and/or 500 and/or
devices 200, 300, and/or 400 may be configured as a self-contained
unit that includes all functionalities necessary for operation of
the device and/or apparatus, or configured as one or more subparts
in one or more locations separate from one another, wherein one or
more of the subparts includes one or more essential and/or
non-essential functionalities. In illustrative examples, one
subpart may be placed within a lumen of, for example, a blood
vessel, and another subpart placed, for example, sub-cutaneously or
within a larger or more accessible lumen. In illustrative
embodiments, a remote portion may provide for monitoring of the
lumen-based device or data collection or analysis. The remote
portion may be at a separate location within the body of the
subject, or outside the body of the subject. Data and/or power
signals may be transmitted between the one or more subparts using
electromagnetic signals, for example, or electrical or optical
links. Methods of distributing functionalities of a system between
hardware, firmware, and software at located at two or more sites
are well known to those of skill in the art.
[0044] Embodiments of one or more apparatus 100 and/or 500 may be
configured as a handheld unit, optionally self-contained and/or
with one or more subparts in one or more other locations. In
illustrative embodiments, a hand held unit includes one or more
sources of energy 110, and at least one monitor to provide viewing
of the lesion and targeting electromagnetic energy 118. In
illustrative embodiments, a hand held unit includes control
circuitry and at least one monitor for viewing lesion targeting
information, as well as being connected to an energy source 110 and
optionally one or more power sources 140 through one or more
conduits. In illustrative embodiments, a handheld unit is
wirelessly connected to control circuitry and to a monitor
providing targeting information to an operator. In illustrative
embodiments, apparatus 100 is a mounted, non-handheld, unit.
[0045] Embodiments of one or more apparatus 100 and/or 500 and/or
devices 200, 300, and/or 400 may be described as having one or more
subparts including, but not limited to, one or more energy sources
110, one or more sensors 120, one or more control circuitry 130,
one or more power sources 140, and/or one or more motive sources
150. In some embodiments, one or more subpart may be a physically
distinct unit. In some embodiments, one or more subpart is combined
with one or more other subpart to form a single unit with no
physically discernible separation. Some embodiments include a
first, second, third, fourth, fifth, etc. energy source 110, sensor
120, control circuitry 130, power source 140, and/or motive source
150. One or more of the one, two three, four, five, etc. components
may be the same component and/or physical entity, or one or more
components may be a separate physical entity. For example, there
may be two lasers in a device, or there may be one laser able to
provide both excitation and ablation energy. For example, there may
be two sensors in a device, or there may be one sensor able to
detect a variety of energy wavelengths.
[0046] As used herein, the term "lesion" may include wounds,
incisions, and/or surgical margins. In some embodiments, the term
"lesion" may include, but is not limited to, cells and/or tissues,
optionally including cells and/or tissues of the skin and/or
retina. Wounds may include, but are not limited to, scrapes,
abrasions, cuts, tears, breaks, punctures, gashes, slices, and/or
any injury resulting in bleeding and/or skin trauma sufficient for
foreign organisms to penetrate. Incisions may include those made by
a medical professional, such as but not limited to, physicians,
nurses, mid-wives, and/or nurse practitioners, dental
professionals, such as but not limited to, dentists, orthodontists,
dental hygienists, and veterinary professionals, including but not
limited to, veterinarians during treatment optionally including
surgery. As used herein, the term "surgical margins" may include
the edges of incisions, for example, cancer margins.
[0047] As used herein, the term "lumen" may include, but is not
limited to, part or all of a nostril or nasal cavity, the
respiratory tract, the cardiovascular system (e.g., a blood vessel,
including for example, arteries, veins, and capillaries), the
lymphatic system, the biliary tract, the urogenital tract (e.g. a
ureter), the oral cavity, the digestive tract, the tear ducts, a
glandular system, a male or female reproductive tract (e.g.
fallopian tubes, uterus, the epididymis, vas deferens, ductal
deferens, efferent duct, ampulla, seminal duct, ejaculatory duct,
and/or urethra), the cerebral-spinal fluid space (e.g. the cerebral
ventricles, the subarachnoid space, and/or the spinal canal), the
thoracic cavity, the abdominal cavity, and other fluid-containing
structures of an organism. Other lumens may be found in the
auditory or visual system, or in interconnections thereof, e.g.,
the Eustachian tubes.
[0048] Also included within the scope of the term "lumen" are
man-made lumens within the body, including vascular catheters,
spinal fluid shunts, vascular grafts, bowel re-anastomoses, bypass
grafts, indwelling stents of various types (e.g., vascular,
gastrointestinal, tracheal, respiratory, urethral, genitourinary,
etc.) and surgically created fistulas. Other man-made lumens may be
found associated with one or more implants, such as but not limited
to, partial and/or complete joint replacements (knee, hip,
shoulder, ankle, etc.) and/or partial and/or complete bone
replacements (spinal vertebra, femur, shin, etc.).
[0049] As used herein, the term "internal location" may include
locations within the body of a subject appropriate for the
placement of one or more device and/or apparatus. Internal
locations may be natural and/or man-made. In illustrative
embodiments, one or more devices and/or subparts may be associated
with one or more manmade objects within a subject, such as but not
limited to, one or more stents, screws, rods, artificial joints,
etc. Such internal locations are known to those with skill in the
art and/or described herein.
[0050] As used herein, the term "in proximity to" may include, but
is not limited to, a space and/or area near to a defined area, such
as a lesion, lumen and/or internal location. Locations that are in
proximity to a lumen may include, for example, locations internal
to the lumen, parts, or all, of the width of the lumen wall, and
locations external to the lumen wall. In some embodiments, "in
proximity to" may include distances such as, but not limited to,
approximately 0.1, 1.0, 10, and/or 100 .mu.ms and/or 0.1, 1.0, 10,
and/or 100 mms, and may optionally include larger and/or smaller
distances depending on the energy provided (e.g. electromagnetic
energy, particle beam, two-photon, pulsed, etc.) and/or the
sensitivity of detection. Those of skill in the art would know
(and/or are able to calculate) the applicable distance for each
form of energy.
[0051] As used herein, the term "subject" may include, but is not
limited to, one or more living entities including, but not limited
to, animals, mammals, humans, reptiles, birds, amphibians, and/or
fish. The animals may include, but are not limited to,
domesticated, wild, research, zoo, sports, pet, primate, marine,
and/or farm animals. Animals include, but are not limited to,
bovine, porcine, swine, ovine, murine, canine, avian, feline,
equine, and/or rodent animals. Domesticated and/or farm animals
include, but are not limited to, chickens, horses, cattle, pigs,
sheep, donkeys, mules, rabbits, goats, ducks, geese, chickens,
and/or turkeys. Wild animals include, but are not limited to,
non-human primates, bear, deer, elk, raccoons, squirrels, wolves,
coyotes, opossums, foxes, skunks, and/or cougars. Research animals
include, but are not limited to, rats, mice, hamsters, guinea pigs,
rabbits, pigs, dogs, cats and/or non-human primates. Pets include,
but are not limited to, dogs, cats, gerbils, hamsters, guinea pigs
and/or rabbits. Reptiles include, but are not limited to, snakes,
lizards, alligators, crocodiles, iguanas, and/or turtles. Avian
animals include, but are not limited to, chickens, ducks, geese,
owls, sea gulls, eagles, hawks, and/or falcons. Fish include, but
are not limited to, farm-raised, wild, pelagic, coastal, sport,
commercial, fresh water, salt water, and/or tropical. Marine
animals include, but are not limited to, whales, sharks, seals, sea
lions, walruses, penguins, dolphins, and/or fish.
[0052] The dimensions and mechanical properties (e.g., rigidity) of
the one or more apparatus 500 and/or devices 200, 300, and/or 400,
and particularly of the structural elements of the one or more
apparatus and/or device, may be selected for compatibility with the
location of use in order to provide for reliable positioning and/or
to provide for movement of the apparatus and/or device while
preventing damage to the lesion, lumen, and/or internal location
and its surrounding structure. In illustrative embodiments, an
apparatus and/or device may be internal or external, tethered or
untethered, motile or immobile, and/or optionally ingestible.
[0053] The choice of structural element size and configuration
appropriate for a particular body lumen and/or internal location
may be selected by a person of skill in the art. Structural
elements may be constructed using a variety of manufacturing
methods, from a variety of materials. Appropriate materials may
include metals, ceramics, polymers, and composite materials having
suitable biocompatibility, sterilizability, mechanical, and
physical properties, as will be known to those of skill in the art.
Examples of materials and selection criteria are described, for
example, in The Biomedical Engineering Handbook (Second Edition,
Volume I, J. D. Bronzino, Ed., Copyright 2000, CRC Press LLC, pp.
IV-1-43-31). Manufacturing techniques may include injection
molding, extrusion, die-cutting, rapid-prototyping, etc., and will
depend on the choice of material and device size and configuration.
Sensing and energy-emitting portions of the devices as well as
associated control circuitry may be fabricated on the structural
elements using various microfabrication and/or MEMS techniques
(see, e.g., U.S. Patent Applications 2005/0221529, 2005/0121411,
2005/0126916, and Nyitrai, et al. "Preparing Stents with Masking
& Etching Technology" (2003) 26.sup.th International Spring
Seminar on Electronics Technology pp. 321-324, IEEE), or may be
constructed separately and subsequently assembled to the structural
elements, as one or more distinct components. See also, U.S. patent
application Ser. Nos. 11/403,230 and 11/645,357.
[0054] The choice of structural element size and configuration
appropriate for a motile, optionally affixable, device may be
selected by a person of skill in the art. Configurations for
structural elements of motile devices include, but are not limited
to, a substantially tubular structure, one or more lumens in fluid
communication with the body lumen, and/or an adjustable diameter
(see, e.g., U.S. patent application Ser. Nos. 11/403,230 and
11/645,357). Structural elements may have the form, for example, of
a short cylinder, an annulus, a cylinder, and/or a spiral. A spiral
structure is disclosed, for example, in Bezrouk et al,
("Temperature Characteristics of Nitinol Spiral Stents" (2005)
Scripta Medica (BRNO) 78(4):219-226. Elongated forms such as
cylinders or spirals may be suitable for use in tubular
lumen-containing structures such as, for example, blood
vessels.
[0055] In additional to materials disclosed above, flexible
material having adjustable diameter, taper, and length properties
may be used as part of the structural material. For example, some
materials may change from a longer, narrower configuration, to a
shorter, wider configuration, or may taper over their length.
Structural elements that may exhibit this type of
expansion/contraction property may include mesh structures formed
of various metals or plastics, and some polymeric materials, for
example (see, e.g., "Agile new plastics change shape with heat" MIT
News Office (Nov. 20, 2006) pp. 1-4; MIT Tech Talk (Nov. 22, 2006)
p.5; http://web.mit.edu/newsoffice/2006/triple-shape.html; and
Shanpoor et al., Smart Materials and Structures (2005) 14:197-214,
Institute of Physics Publishing).
[0056] In some embodiments, the structural element may include a
self-expanding material, a resilient material, or a mesh-like
material. Flexibility may also be conferred by configuration as
well as material; the structural element may include a slotted
structure and/or mesh-like material, for example. Structural
elements may be formed from various materials, including metals,
polymers, fabrics, and various composite materials, including ones
of either inorganic or organic character, the latter including
materials of both biologic and abiologic origin, selected to
provide suitable biocompatibility and mechanical properties. The
structural element may include a biocompatible material, and may
include a bioactive component (such as a drug releasing coating or
bioactive material attached to or incorporated into the structural
element).
[0057] It is contemplated that additional components, such as
energy sources 110, sensors 120, control circuitry 130, power
sources 140, and/or motive sources 150 (e.g. propelling
mechanisms), for example, will be attached, connected to, place
within, manufactured on or in, and/or formed integrally with the
structural element. Methods for manufacture and/or assembly are
known in the art and/or described herein.
[0058] Embodiments of one or more apparatus 100 and/or 500 and/or
devices 200, 300, and/or 400 may include one or more energy sources
110. One or more energy sources 110 may include, but are not
limited to, one or more electromagnetic energy sources 111 and/or
one or more charged particle energy sources 112. One or more
electromagnetic energy sources 111 may include, but are not limited
to, one or more optical energy sources 113 and/or one or more X-ray
energy sources 115. One or more optical energy sources 113 may
include, but are not limited to, one or more visual energy sources
114. In some embodiments one or more electromagnetic energy source
111 is a laser.
[0059] In some embodiments, one or more apparatus 100 and/or 500
is, in whole or in part, handheld. In some embodiments one or more
energy source 110, optionally one or more electromagnetic energy
source 111, is handheld. In some embodiments one or more energy
source 110, optionally one or more electromagnetic energy source
111, is in the same handheld unit. In some embodiments one or more
energy source 110, optionally one or more electromagnetic energy
source 111, is in a different handheld unit.
[0060] In some embodiments, one or more energy sources 110
optionally provide energy for excitation of a fluorescent response
116, energy for targeting 118, and/or energy for ablation 117 of
one or more targets. In some embodiments, one energy source 110
provides excitation energy 116, targeting energy 118, and ablation
energy 117. In some embodiments, different energy sources 110
provide excitation energy 116, targeting energy 118, and ablation
energy 117. In some embodiments, one energy source 110 provides
excitation energy 116 and ablation energy 117, and optionally
targeting energy 118. In some embodiments, more than one energy
source 110 provides excitation energy 116. In some embodiments,
more than one energy source provides ablation energy 117.
[0061] In some embodiments, one or more electromagnetic energy
sources 111 provide one or more of excitation energy 116, ablation
energy 117, and/or targeting energy 118. In some embodiments, one
or more optical energy sources 113 (optionally visual energy
sources 114) provide one or more of excitation energy 116, ablation
energy 117, and/or targeting energy 118. In some embodiments, one
or more X-ray energy sources 115 provide ablation energy. In some
embodiments, one or more particle beam sources 112 provide ablation
energy.
[0062] In some embodiments, one or more energy sources 110 are
programmable, remote-controlled, wirelessly controlled, and or
feedback-controlled.
[0063] As used herein, the term "electromagnetic energy" may
include radio waves, microwaves, terahertz radiation, infrared
radiation, visible light, X-rays, and gamma rays. In some
embodiments, one or more of these frequencies may be explicitly
excluded from the general category of electromagnetic energy (e.g.
electromagnetic energy sources, but not including X-ray energy
sources). Electromagnetic energy (or radiation) with a wavelength
between approximately 400 nm and 700 nm is detected by the human
eye and perceived as visible light. Optical light may also include
near infrared (longer than 700 nm) and ultraviolet (shorter than
400 nm). In illustrative embodiments, electromagnetic energy is
generated at one or more wavelengths of approximately 100-280 nm,
180-350 nm, 200-340 nm, 250-400 nm, 250-450 nm, 280-315 nm, 280-540
nm, 300-460 nm, 300-600 nm, 300-700 nm, 310-510 nm, 315-400 nm,
350-390 nm, 350-700 nm, 360-370 nm, 360-600 nm, 375-425 nm, 375-440
nm, 400-1000 nm, 407-420 nm, 410-430 nm, 445-470 nm, 450-490 nm,
450-560 nm, 455-490 nm, 465-495 nm, 490-690 nm, 505-550 nm, 515-555
nm, 580-600 nm, 600-1600 nm, 250 nm, 265 nm, 290 nm, 330 nm, 335
nm, 337 nm, 340 nm, 350 nm, 352 nm, 360 nm, 365 nm, 385 nm, 395 nm,
400 nm, 405 nm, 410 nm, 420 nm, 430 nm, 435 nm, 436 nm, 440 nm, 444
nm, 450 nm, 455 nm, 460 nm, 465 nm, 469 nm, 470 nm, 480 nm, 481 nm,
483 nm, 485 nm, 486 nm, 487 nm, 488 nm, 490 nm, 495 nm, 500 nm, 506
nm, 514 nm, 516 nm, 520 nm, 530 nm, 538 nm, 545 nm, 546 nm, 550 nm,
560 nm, 570 nm, 581 nm, 585 nm, 600 nm, 609 nm, 610 nm, 620 nm, 630
nm, 632 nm, 635 nm, 636 nm, 640 nm, 644 nm, 665 nm, 670 nm, 700 nm,
880 nm, 950 nm, 1064 nm, 1320 nm, 2070 nm, and/or 2940 nm, among
others.
[0064] As used herein, the term "charged particle" may include
particles generated using one or more particle beams. A particle
beam is optionally an accelerated stream of charged particles or
atoms that may be directed by magnets and focused by electrostatic
lenses, although they may also be self-focusing. Particle beams may
be high energy beams (e.g. created in particle accelerators),
medium and/or low energy beams.
[0065] Electromagnetic or optical energy is made up of photons.
Electromagnetic energy includes, but is not limited to, single
photon electromagnetic energy, two photon electromagnetic energy,
multiple wavelength electromagnetic energy, and extended-spectrum
electromagnetic energy. Electromagnetic energy may be used for
excitation of fluorescence, targeting, and/or for ablation of one
or more targets. As used herein, the term "fluorescence" may
include the production of light (emission) following excitation by
electromagnetic energy. Fluorescence may result from emissions from
exogenously provided tags and/or markers, and/or an inherent
response of one or more targets to excitation with electromagnetic
energy. As used herein, the term "auto-fluorescence" may include an
inherent fluorescent response from one or more targets.
[0066] Electromagnetic energy sources 111 may be configured to emit
energy as a continuous beam or as a train of short pulses. In the
continuous wave mode of operation, the output is relatively
consistent with respect to time. In the pulsed mode of operation,
the output varies with respect to time, optionally having
alternating `on` and `off` periods. In illustrative examples, one
or more energy sources are configured to emit pulsed energy to
specifically ablate a limited area and/or a limited number of
target cells. In illustrative examples, one or more energy sources
are configured to emit continuous energy to excite endogenous
fluorophores to emit fluorescence.
[0067] One or more electromagnetic energy sources 111 may include
one or more lasers having one or more of a continuous or pulsed
mode of action. One or more pulsed lasers may include, but are not
limited to, Q-switched lasers, mode locking lasers, and
pulsed-pumping lasers. Mode locked lasers emit extremely short
pulses on the order of tens of picoseconds down to less than 10
femtoseconds, the pulses optionally separated by the time that a
pulse takes to complete one round trip in the resonator cavity. Due
to the Fourier limit, a pulse of such short temporal length may
have a spectrum which contains a wide range of wavelengths.
[0068] In some embodiments, the electromagnetic energy is focused
at a depth of approximately 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm,
0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.0 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4
mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 2.0 mm, 2.1 mm, 2.2 mm,
2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, or 3.0 mm
below the surface of the lesion, beyond the surface of a wall of
the lumen, and/or beyond a surface of an internal location. In some
embodiments, the electromagnetic energy is focused at a depth of
approximately 0.1 to 3 mm, 0.1 to 2.5 mm, 0.1 to 2.0 mm, 0.1 to 1.5
mm, 0.1 to 1.0 mm, 0.1 to 0.5 mm, 0.5 to 3.0 mm, 0.5 to 2.5 mm, 0.5
to 2.0 mm, 0.5 to 1.5 mm, 0.5 to 1.0 mm, 1.0 to 3.0 mm, 1.0 to 2.5
mm, 1.0 to 2.0 mm, 1.0 to 1.5 mm, 1.5 to 3.0 mm, 1.5 to 2.5 mm, 1.5
to 2.0 mm, 2.0 to 3.0 mm, 2.0 to 2.5 mm, or 2.5 to 3.0 mm below the
surface of the lesion, beyond the surface of a wall of the lumen,
and/or beyond a surface of an internal location.
[0069] In some embodiments, the electromagnetic energy is generated
by two photons having the same wavelength. In some embodiments, the
electromagnetic energy is generated by two photons having a
different wavelength. Electromagnetic energy generated by two
photons is optionally focused at a depth below the surface of the
lesion, beyond the surface of a wall of the lumen, and/or beyond a
surface of an internal location, optionally at one or more depths
as described above and/or herein.
[0070] As used herein, the term "two-photon" may include excitation
of a fluorophore by two photons in a quantum event, resulting in
the emission of a fluorescence photon, optionally at a higher
energy than either of the two excitatory photons, optionally using
a femtosecond laser. In some embodiments, two photon
electromagnetic energy is coupled through a virtual energy level
and/or coupled through an intermediate energy level.
[0071] As used herein, the term "extended-spectrum" may include a
range of possible electromagnetic radiation wavelengths within the
full spectrum of possible wavelengths, optionally from extremely
long to extremely short. One of skill in the art is able to select
appropriate ranges for the devices and methods disclosed herein
based on information publicly available and/or disclosed
herein.
[0072] In some embodiments, the electromagnetic energy may be
defined spatially and/or directionally. In some embodiments, the
electromagnetic energy may be spatially limited, optionally
spatially focused and/or spatially collimated. In illustrative
embodiments, the electromagnetic energy optionally contacts less
than less than an entire possible area, or an entire possible
target, and/or is limited to a certain depth within a tissue.
[0073] In some embodiments, the electromagnetic energy may be
directionally limited, directionally varied, and/or directionally
variable. In illustrative embodiments, the electromagnetic energy
may be provided only in a single direction, for example 90 degrees
from the horizontal axis of a device, or toward a lumen wall, a
lesion, or an internal location. In illustrative embodiments, the
electromagnetic energy may be provided over a range of directions
for example, through movement of the electromagnetic source,
through movement of the entire device (e.g. rotation, random
movement, wobbling, tumbling), and/or through illumination from a
variety of sources in the device.
[0074] Electromagnetic energy configured to induce a fluorescent
response in a target may be selected, optionally manually,
remotely, programmably, wirelessly, and/or using feedback
information. Frequencies that induce a fluorescent response in one
or more targets are known in the art and/or discussed herein. In
some embodiments, selection of excitation energy 116 may be
performed in advance, or as a result of information received,
optionally including feedback information, optionally from one or
more sensors 120.
[0075] Electromagnetic energy and/or particle beam energy
configured to ablate one or more targets may be selected,
optionally manually, remotely, programmably, wirelessly, and/or
using feedback information. Frequencies useful to at least
partially ablate one or more targets are known in the art and/or
discussed herein. In some embodiments, selection of ablation energy
117 may be performed in advance, or as a result of information
received, optionally including feedback information, optionally
from one or more sensors 120.
[0076] In addition to electromagnetic energy described herein, the
ablation energy may be supplied by energetic charged particles,
such as electrons, protons, or other ions. In one embodiment, the
charged particles are directed towards the autofluorescent target
in the form of particle beams. In another embodiment, the charged
particles are emitted over relatively wide solid-angles, and
address the designated autofluorescent target by virtue of spatial
proximity.
[0077] In one embodiment, particle beams are generated outside the
body by beam generators such as particle accelerators, cathode ray
tubes, electrostatic accelerators, voltage-multiplier accelerators,
Cockcroft-Walton accelerators, Van de Graaff accelerators, Alvarez
accelerators, linear accelerators, circular accelerators, wakefield
accelerators, collimated radioactive emitters, etc. The beams from
these sources can be directed towards the autofluorescent target by
mechanical, electrical, or magnetic methods. In some embodiments,
the particle beams may be generated and directed from locations
separate from the light source used to induce the autofluorescent
response. In other embodiments, the particle beam may be generated
in proximity to the autofluorescence inducing light source, by
using compact particle sources such as electrostatic accelerators,
Alvarez accelerators, linear accelerators, voltage-multiplier
accelerators, Cockcroft-Walton accelerators, wakefield
accelerators, collimated radioactive emitters, etc.
[0078] In some embodiments, particle beams are generated and
delivered from inside the body. Compact particle beam generators
such as electrostatic accelerators, Alvarez accelerators, linear
accelerators, voltage-multiplier accelerators, Cockcroft-Walton
accelerators, or wakefield accelerators can be used. In one
embodiment of a voltage-multiplier accelerator, the staged voltage
elements can use high-field-strength capacitors. In another
embodiment, the staged voltages can be generated in an array of
photocells by photogeneration using on-board or off-board light
sources. In another embodiment of an in-vivo particle source, a
radioactive emitter can be used to provide a charged particle
source. One example of such a source is the Beta-Cath.TM. System,
developed by Novoste Corp.
[0079] In one embodiment, in-vivo radioactive sources can be
encapsulated within shielding which can be used to control charged
particle exposure to nearby tissue. The shielding can have one or
more portals, allowing for collimated emission. The shielding can
be movable, either across all or part of its extent, or across one
or more portal openings, in order to provide switchable particle
sources. Shielding can be controllably moved by mechanical
techniques such as valves, shutters, or similar devices, can
utilize movable liquids, such as Hg, or utilize other methods. The
particles from these in-vivo sources can be directed towards the
autofluorescent target by mechanical, electrical, or magnetic
methods, or may rely upon proximity.
[0080] Embodiments of one or more apparatus 100 and/or 500 and/or
devices 200, 300, and/or 400 may include one or more targeting
electromagnetic energy sources 118. Targeting electromagnetic
energy is optionally from one or more optical energy sources 113,
optionally from one or more visible light sources 114. In some
embodiments, the one or more targeting energy source 118 is aligned
with the excitation energy source 116 and/or the ablation energy
source 117. In illustrative embodiments, the targeting energy
source 118 provides a visual indication of the directional
alignment of the excitation energy 116 to induce a fluorescent
response, and/or the ablation energy 117 to at least partially
ablate one or more targets.
[0081] In some embodiments, the one or more targeting energy source
118 has the same spatial extent as the excitation energy 116 and/or
the ablation energy 117. In some embodiments, the one or more
targeting energy source 118 has a different spatial extent than the
excitation energy 116 and/or the ablation energy 117. In
illustrative embodiments, the targeting energy is a visually
detectable beam of light that is narrower than the excitation
energy and/or ablation energy beam. In illustrative embodiments,
the targeting energy is a visually detectable beam of light that is
focused at the midpoint of the excitation and/or ablation energy
beam. In illustrative embodiments, the targeting energy is a
visually detectable beam of light that is broader than the
excitation and/or ablation energy beam.
[0082] Embodiments of one or more apparatus 100 and/or 500 and/or
devices 200, 300, and/or 400 may include one or more sensors 120.
In some embodiments, one or more sensors 120 are the same sensor.
In some embodiments, one or more sensors 120 are different sensors.
In some embodiments, one or more sensors are in the same unit,
optionally a handheld unit. In some embodiments, one or more
sensors 120 are in separate units. In some embodiments, one or more
sensors 120 are in the same and/or different units than one or more
energy sources 110.
[0083] The one or more sensors may include, but are not limited to,
electromagnetic energy detectors 121 (e.g. optical energy such as
near IR, UV, visual), pH detectors 122, chemical and biological
molecule detectors 123 (e.g. blood chemistry, chemical
concentration, biosensors), physiological detectors 124 (e.g. blood
pressure, pulse, peristaltic action, pressure sensors, flow
sensors, viscosity sensors, shear sensors), time detectors 125
(e.g. timers, clocks), imaging detectors 126, acoustic sensors 127,
temperature sensors 128, and/or electrical sensors 129. One or more
sensors may be configured to measure various parameters, including,
but not limited to, the electrical resistivity of the fluid, the
density or sound speed of the fluid, the pH, the osmolality, or the
index of refraction of the fluid at least one wavelength. The
selection of a suitable sensor for a particular application or use
site is considered to be within the capability of a person having
skill in the art. One or more of these and/or other sensing
capabilities may be present in a single sensor or an array of
sensors; sensing capabilities are not limited to a particular
number or type of sensors.
[0084] One or more biosensors 123 may detect materials including,
but not limited to, a biological marker, an antibody, an antigen, a
peptide, a polypeptide, a protein, a complex, a nucleic acid, a
cell (and, in some cases, a cell of a particular type, e.g. by
methods used in flow cytometry), a cellular component, an
organelle, a gamete, a pathogen, a lipid, a lipoprotein, an
alcohol, an acid, an ion, an immunomodulator, a sterol, a
carbohydrate, a polysaccharide, a glycoprotein, a metal, an
electrolyte, a metabolite, an organic compound, an organophosphate,
a drug, a therapeutic, a gas, a pollutant, or a tag. A biosensor
123 may include an antibody or other binding molecule such as a
receptor or ligand.
[0085] One or more sensors optionally include, in part or whole, a
gas sensor such as an acoustic wave, chemiresistant, or
piezoelectric sensors, or an electronic nose. One or more sensors
are optionally small in size, for example a sensor or array that is
a chemical sensor (Snow (2005) Science 307:1942-1945), a gas sensor
(Hagleitner, et al. (2001) Nature 414:293-296.), an electronic
nose, and/or a nuclear magnetic resonance imager (Yusa (2005),
Nature 434:1001-1005). Further examples of sensors are provided in
The Biomedical Engineering Handbook, Second Edition, Volume I, J.
D. Bronzino, Ed., Copyright 2000, CRC Press LLC, pp. V-1-51-9, and
U.S. Pat. No. 6,802,811).
[0086] One or more electromagnetic energy sensors 121 may be
configured to measure the absorption, emission, fluorescence, or
phosphorescence of one or more targets. Such electromagnetic
properties may be inherent properties of all or a portion of one or
more targets (e.g. auto-fluorescence), or may be associated with
materials added or introduced to the body, surface, lumen,
interior, and/or fluid, such as tags or markers for one or more
targets. One or more targets may include, but are not limited to,
at least a portion of one or more of a wound, a lesion, and/or an
incision, one or more internal surfaces, one or more lumen fluids,
one or more cells, one or more lumen walls, and/or one or more
other interior locations.
[0087] In some embodiments, one or more sensors 120 are configured
to detect a fluorescent response at a single wavelength of
electromagnetic energy, at two wavelengths of electromagnetic
energy, at multiple wavelengths of electromagnetic energy, or over
extended-spectrum electromagnetic energy. In some embodiments, one
or more sensors 120 are configured to detect excitation energy,
ablation energy, and/or targeting energy. In illustrative
embodiments, one or more sensors are configured to detect
wavelengths of approximately 100-280 nm, 180-350 nm, 200-340 nm,
250-400 nm, 250-450 nm, 280-315 nm, 280-540 nm, 300-460 nm, 300-600
nm, 300-700 nm, 310-510 nm, 315-400 nm, 350-390 nm, 350-700 nm,
360-370 nm, 360-600 nm, 375-425 nm, 375-440 nm, 400-1000 nm,
407-420 nm, 410-430 nm, 445-470 nm, 450-490 nm, 450-560 nm, 455-490
nm, 465-495 nm, 490-690 nm, 505-550 nm, 515-555 nm, 580-600 nm,
600-1600 nm, 250 nm, 265 nm, 290 nm, 330 nm, 335 nm, 337 nm, 340
nm, 350 nm, 352 nm, 360 nm, 365 nm, 385 nm, 395 nm, 400 nm, 405 nm,
410 nm, 420 nm, 430 nm, 435 nm, 436 nm, 440 nm, 444 nm, 450 nm, 455
nm, 460 nm, 465 nm, 469 nm, 470 nm, 480 nm, 481 nm, 483 nm, 485 nm,
486 nm, 487 nm, 488 nm, 490 nm, 495 nm, 500 nm, 506 nm, 514 nm, 516
nm, 520 nm, 530 nm, 538 nm, 545 nm, 546 nm, 550 nm, 560 nm, 570 nm,
581 nm, 585 nm, 600 nm, 609 nm, 610 nm, 620 nm, 630 nm, 632 nm, 635
nm, 636 nm, 640 nm, 644 nm, 665 nm, 670 nm, 700 nm, 880 nm, 950 nm,
1064 nm, 1320 nm, 2070 nm, and/or 2940 nm.
[0088] In some embodiments, one or more sensors 120 are configured
to detect a cumulative fluorescent response over a time interval.
In some embodiments, one or more sensors 120 are configured to
detect a fluorescent response at a specific time interval and/or at
a specific time. In some embodiments, one or more sensors 120 are
configured to detect a time-dependent fluorescent response. In
illustrative embodiments, the cumulative fluorescent response is
determined over milliseconds, seconds, and/or minutes following
excitation. In some embodiments, the fluorescent response is
detected over millisecond, second, and/or minute time intervals
following excitation. In some embodiments, the fluorescent response
is detected approximately femtoseconds, picoseconds, nanoseconds,
milliseconds, seconds, and/or minutes after excitation.
[0089] In some embodiments, one or more sensors 120 are configured
to be calibrated optionally at least partially based an expected
baseline fluorescence (e.g. normal fluorescence) for the fluid,
tissue, cells, internal location, lesion, and/or lumen. As used
herein, the term "normal fluorescence" may include the intrinsic
fluorescence of one or more fluid, tissue, cells, internal
location, lesion, and/or lumen as determined by researchers and/or
medical or veterinary professionals for subjects of a certain age,
ethnicity, etc. who do not have pathological conditions (e.g.
control subjects). "Normal fluorescence" may include the intrinsic
fluorescence of fluid, tissue, cells, internal location, lesion,
and/or lumen of a subject prior to a pathological condition and/or
of a comparable location not affected by the pathological
condition.
[0090] Embodiments of one or more apparatus 100 and/or 500 and/or
devices 200, 300, and/or 400 may be configured to detect a
condition of interest including, but not limited to, a temperature,
a pressure, a fluid flow, an optical absorption, optical emission,
fluorescence, or phosphorescence, an index of refraction at least
one wavelength, an electrical resistivity, a density or sound
speed, a pH, an osmolality, the presence of an embolism, the
presence (or absence) of an object (such as a blood clot, a
thrombus, an embolus, a plaque, a lipid, a kidney stone, a dust
particle, a pollen particle, a gas bubble, an aggregate, a cell, a
specific type of cell, a cellular component or fragment, a
collection of cell, a gamete, a pathogen, or a parasite), and/or
the presence (or absence) of a substance such as a biological
marker, an antibody, an antigen, a peptide, a polypeptide, a
protein, a complex, a nucleic acid, a cell (and, in some cases, a
cell of a particular type, e.g. by methods used in flow cytometry),
a cellular component, an organelle, a gamete, a pathogen, a lipid,
a lipoprotein, an alcohol, an acid, an ion, an immunomodulator, a
sterol, a carbohydrate, a polysaccharide, a glycoprotein, a metal,
an electrolyte, a metabolite, an organic compound, an
organophosphate, a drug, a therapeutic, a gas, a pollutant, or a
tag, for example.
[0091] As used herein, the term "target" may include a condition
and/or material of interest. Materials of interest may include, but
are not limited to, materials identifiable by their autofluorescent
emissions (individually or as an aggregate signal), or through the
use of tags detectable through fluorescence. Such materials may
include, but are not limited to, target cells, target tissues,
and/or target areas. Such targets may include, but are not limited
to, a blood clot, a thrombus, an embolus, a plaque, a lipid, a
kidney stone, a dust particle, a pollen particle, an aggregate, a
cell, a specific type of cell, a cellular component, an organelle,
a collection or aggregation of cells or components thereof, a
gamete, a pathogen, or a parasite.
[0092] One or more targets may include, but are not limited to,
cancer, microbial cells, infected cells, and/or atherosclerotic
cells. One or more cancer cells may include, but are not limited
to, neoplastic cells, metastatic cancer cells, precancerous cells,
adenomas, and/or cancer stem cells. Cancer types may include, but
are not limited to, bladder cancer, breast cancer, colon cancer,
rectal cancer, endometrial cancer, kidney (renal) cancer, lung
cancer, leukemia, melanoma, non-Hodgkin's Lymphoma, pancreatic
cancer, prostate cancer, skin (non-melanoma) cancer, and thyroid
cancer. Cancers may include, but are not limited to, bone, brain,
breast, digestive, gastrointestinal, endocrine, eye, genitourinary,
germ line, gynecological, head and neck, hematologic/blood,
leukemia, lymphoma, lung, musculoskeletal, neurologic,
respiratory/thoracic, skin, and pregnancy-related. Microbial cells
(microorganisms) may include, but are not limited to, bacteria,
protists, protozoa, fungi, and/or amoeba. Pathogens may include,
but are not limited to, bacteria, viruses, parasites, protozoa,
fungi, and/or proteins. Bacteria may include, but are not limited
to, Escherichia coli, Salmonella, Mycobacterium spp., Bacillus
anthracis, Streptococcus spp., Staphylococcus spp., Francisella
tularensis, and/or Helicobacter pylori. Viruses may include, but
are not limited to, Hepatitis A, B, C, D, and/or E, Influenza
virus, Herpes simplex virus, Molluscum contagiosum, and/or Human
Immunodeficiency virus. Protozoa may include, but are not limited
to, Cryptosporidium, Toxoplasma spp., Giardia lamblia, Trypanosoma
spp., Plasmodia spp. and/or Leishmania spp. Fungi may include, but
are not limited to, Pneumocystis spp., Tinea, Candida spp.,
Histoplasma spp., and/or Cryptococcus spp. Parasites may include,
but are not limited to tapeworms and/or roundworms. Proteins may
include, but are not limited to, prions.
[0093] As used herein, the term "fluid" may refer to liquids,
gases, and other compositions, mixtures, or materials exhibiting
fluid behavior. The fluid within the body lumen may include a
liquid, or a gas or gaseous mixtures. As used herein, the term
fluid may encompass liquids, gases, or mixtures thereof that also
include solid particles in a fluid carrier. Liquids may include
mixtures of two or more different liquids, solutions, slurries, or
suspensions. Examples of liquids present within body lumens
include, but are not limited to, blood, lymph, serum, urine, semen,
digestive fluids, tears, saliva, mucous, cerebro-spinal fluid,
intestinal contents, bile, epithelial exudate, or esophageal
contents. Liquids present within body lumens may include synthetic
or introduced liquids, such as blood substitutes, or drug,
nutrient, fluorescent marker, or buffered saline solutions. Fluids
may include liquids containing dissolved gases or gas bubbles, or
gases containing fine liquid droplets or solid particles. Gases or
gaseous mixtures found within body lumens may include inhaled and
exhaled air, e.g. in the nasal or respiratory tract, or intestinal
gases.
[0094] Embodiments of one or more apparatus 100 and/or 500 and/or
device 200, 300, and/or 400 may include control circuitry 130. In
some embodiments, the control circuitry is configured to control
one or more of one or more energy sources 110, one or more sensors
120, and/or one or more power sources 140. In some embodiments, the
control circuitry 130 may be directly coupled, indirectly coupled,
and/or wirelessly coupled to one or more energy sources 110, one or
more sensors 120, and/or one or more power sources 140. Control
circuitry 130 may be electrical circuitry and/or other types of
logic/circuitry including, for example, fluid circuitry,
chemo-mechanical circuitry, and other types of logic/circuitry that
provide equivalent functionality. The control circuitry 130 may
include at least one of hardware, software, and firmware; in some
embodiments the control circuitry may include a microprocessor. The
control circuitry 130 may be located in or on the structural
element of a device and/or at a location separate from the
structural element. Various operation flows (e.g. 600, 700, and/or
800) operable on control circuitry 130 are described herein and/or
known in the art.
[0095] In some embodiments, the control circuitry 130 is responsive
to identify a target, target area, and/or target cells, molecules,
and/or tissues. In some embodiments, the control circuitry 130
identifies a target, target area, and/or target cells, molecules,
and/or tissues by determining one or more of the direction, the
distance, the tissue depth, the time, and/or the coordinates from
which a fluorescent response originated, optionally in relation to
the excitation energy 116 and/or the targeting energy 118. In some
embodiments, the control circuitry 130 identifies a target, target
area, and/or target cells, molecules, and/or tissues by analysis of
one or more characteristics of a fluorescent response (e.g.
presence and/or absence of a fluorescent response and/or density of
a fluorescent response--grouping of cells that if non-grouped would
not be considered a target), optionally including but not limited
to, the electromagnetic spectrum, or parts thereof, of a
fluorescent response. In some embodiments, the control circuitry
130 identifies a target, target area, and/or target cells,
molecules, and/or tissues in real time.
[0096] In some embodiments, the control circuitry 130 is responsive
to select one or more characteristics of ablation energy 117 for at
least partially ablating a target, target area, and/or target
cells, molecules, and/or tissues. In some embodiments, the control
circuitry 130 selects one or more characteristics of ablation
energy 117 for at least partially ablating a target, target area,
and/or target cells, molecules, and/or tissues responsive to one or
more characteristics of the fluorescent response and/or the
electromagnetic energy selected to elicit the fluorescent response.
In some embodiments, the control circuitry 130 increases the
ablation energy 117 responsive to an increase in the fluorescent
response, and/or decreases the ablation energy 117 responsive to a
decrease in the fluorescent response. In some embodiments, the
control circuitry 130 selects one or more characteristics of the
ablation energy 117 at least partially responsive to detection of
one or more wavelengths of the fluorescent response.
[0097] In some embodiments, the control circuitry 130 is responsive
to update targeting information on the basis of movement of part or
all of an apparatus 100, and/or 500 and/or a device 100, 200,
and/or 300 and/or a target and/or target area. In illustrative
embodiments, such target updating may be useful when the ablating
energy 117 may be delivered at a time substantially later than the
time at which autofluorescence radiation is detected, or when the
target is moving in relation to the ablation energy source 117. In
this case, the detected location must be updated to take into
account possible motion of the target area and/or the device.
[0098] Motion of the autofluorescence location can be updated by
registering the detected autofluorescence location relative to
other, updatable, location information. In one example, the
detected autofluorescence location is registered relative to
fiducials on or within the individual. Then, the location of the
fiducials is updated, and the site of the autofluorescence location
at such time can be predicted based upon its known registration
relative to the fiducial locations. In another example, the
detected autofluorescence location is registered relative to
features within an image of a related portion of the individual.
Then, the image is updated and the location of the autofluorescence
location at such time can be predicted based upon its known
registration relative to the image features.
[0099] Motion, which may include location and/or orientation, of
the device can be updated by a variety of methods, including
inertial navigation, measurements based on beacons or, fiducials,
measurements based on orientation sensors, or combinations of such
techniques. Inertial navigation can be performed with the support
of accelerometers on the device, and may also incorporate use of
gyroscopic sensors on the device. Beacons and/or fiducials can be
used to measure the device's motion; the beacons or fiducials may
be on the device and their location or direction measured by remote
sensors. Alternatively, measurements of remote beacons or fiducials
may be made by sensors on the device. Combined systems may be used,
with mixtures of remote and on-board sensors, measuring the
location or direction of remote or on-board beacons or fiducials.
Orientation sensors, such as tilt sensors may be used to provide
information of one or more aspects of the device's orientation.
Motion information obtained from different sources or methods can
be combined together to give improved motion estimates, using
techniques such as nonlinear filtering, least-squares filtering,
Kalman filtering, etc.
[0100] The updated autofluorescence location may then be combined,
via a coordinate translation and rotation, with the updated
position and location of the device. This results in updated
coordinates or directions of the autofluorescence location with
respect to the device, and can be used to direct the delivery of
ablation energy.
[0101] In some embodiments, control circuitry receives information
from one or more sensors and/or one or more external sources.
Information may include, but is not limited to, a location of an
untethered device, allowable dose limits (e.g. of energy for
excitation and/or ablation and/or targeting), release authority
(e.g. for release of energy for excitation, ablation, and/or
targeting, and/or release from a tethered location, or from an
affixed and/or stationary location), control parameters (e.g. for
energy release, for motion, for power, for sensors, etc.),
operating instructions, and/or status queries.
[0102] In some embodiments, control circuitry is feedback
controlled, optionally from information from one or more sensors,
and/or one or more external sources. In some embodiments, control
circuitry is monitored by one or more external sources, provides
outputs to one or more sources, and/or sends outputs to one or more
sources. In some embodiments control circuitry is
remote-controlled, wirelessly controlled, programmed, and/or
automatic.
[0103] Embodiments of one or more apparatus 100 and/or 500 and/or
devices 200, 300 and/or 400 optionally include a power source 140.
One or more power sources may be configured to provide power to one
or more of one or more motive sources, one or more control
circuitry, one or more sensor, and/or one or more energy
source.
[0104] Power sources 140 may include, but are not limited to, one
or more batteries 141, fuel cells 142, energy scavenging 143,
electrical 144, and/or receivers 145 located on and/or in the one
or more apparatus and/or devices or separately from the one or more
apparatus and/or devices. The one or more batteries may include a
microbattery such as those available from Quallion LLC
(http://www.quallion.com), may be designed as a film (U.S. Pat.
Nos. 5,338,625 and 5,705,293), or may be a nuclear battery. The one
or more fuel cells may be enzymatic, microbial, or photosynthetic
fuel cells or other biofuel cells (US2003/0152823A1; WO03106966A2
Miniature Biofuel cell; Chen T et al. J. Am. Chem. Soc. 2001, 123,
8630-8631, A Miniature Biofuel Cell), and may be of any size,
including the micro- or nano-scale.
[0105] The one or more energy-scavenging devices may include a
pressure-rectifying mechanism that utilizes pulsatile changes in
blood pressure, for example, or an acceleration-rectifying
mechanism as used in self-winding watches, or other types of flow
rectifying mechanisms capable of deriving energy from other flow
parameters. The one or more electrical power sources may be located
separately from the structural element of the device and connected
to the structural element by a wire, or an optical power source
located separately from the structural element and connected to the
structural element by a fiber-optic line or cable. The one or more
power receivers may be capable of receiving power from an external
source, acoustic energy from an external source, and/or a power
receiver capable of receiving electromagnetic energy (e.g.,
infrared energy) from an external source.
[0106] In illustrative embodiments, one or more power sources 140
are optionally part of and/or are configured to propel, move,
and/or provide power to one or more motive sources 150. One or more
of the propelling mechanisms may include mechanical or
micromechanical structures driven by at least one motor,
micromotor, or molecular motor, or by expansion or change in
configuration of a shape change polymer or metal. A molecular motor
may be a biomolecular motor that runs on a biological chemical such
as ATP, kinesin, RNA polymerase, myosin dynein,
adenosinetriphosphate synthetase, rotaxanes, or a viral protein. In
illustrative embodiments, one or more power sources 140 are
configured to power one or more rotary motors, propellers,
thrusters, and/or provide for jet propulsion, among others.
[0107] In some embodiments, the power source 140 optionally
includes a power transmitter capable of transmitting power from one
or more device to a secondary location. The power transmitter may
be capable of transmitting at least one of acoustic power,
electrical power, or optical power. The secondary location may be,
for example, another device within the body, either in a body lumen
or elsewhere that includes a power receiver and structures for
using, storing and/or re-transmitting the received power.
[0108] Embodiments of one or more devices 200, 300 and/or 400 may
include one or more motive sources 150. The one or more motive
sources 150 are configured for the type and nature of the lumen
and/or internal location to be traveled. A lumen and/or internal
location having a relatively uniform cross-section (height and/or
width) over the length to be traveled may be traversed by most
propelling mechanisms including, but not limited to, mechanisms
that engage the lumen wall on more than one and/or several sides,
that engage the lumen wall on one side only, that are able to
change shape/size (see, e.g., U.S. Patent Application
2005/0177223), and/or that employ more than one means of
propulsion. A lumen and/or internal location that varies
significantly in cross-section over the length to be traveled may
be traversed using some propelling mechanisms including, but not
limited to, those that walk or roll along one side of a lumen,
those that are able to change shape/size, and/or those that employ
more than one mode of propulsion.
[0109] In illustrative embodiments, one or more motive sources 150
may encompass part or all of the structural elements of one or more
devices 200, 300, and/or 400. For example, one or more structural
elements of one or more devices may be substantially cylindrical,
and hollow and tubular in configuration, with a single central
opening, optionally allowing the exterior of the cylindrical
structural element to contact and engage the wall of a lumen, and
the interior of the structural element (within the single central
opening) to optionally form a fluid-contacting portion of the
structural element. Optionally, one or more structural elements of
one or more devices may be approximately hemi-spherical or
hemi-elliptoid, optionally allowing a portion of its cross-section
to contact and/or engage the wall of a lumen without obstructing
the movement of fluid within the body lumen. Optionally, one or
more structural elements of one or more devices may be pill- or
capsule-shaped, and adapted to move through a central portion of a
body lumen. Lumen wall engaging portions may include, but are not
limited to, rotating wheels, projections (e.g. arms), springs,
hooks (e.g. claws), and/or tissue adhesives that are configured to
engage wall portions and optionally to provide mobility to one or
more devices.
[0110] A variety of motive sources 150 applicable for one or more
devices are known in the art and/or described herein. See, for
example, U.S. Pat. Nos. 5,337,732; 5,386,741; 5,662,587; and
6,709,388; and Kassim, et al. "Locomotion Techniques for Robotic
Colonoscopy"; IEEE Engineering in Med & Biol. Mag. (2006) pp.
49-56; Christensen "Musclebot: Microrobot with a Heart" (2004)
Technolegy.com, pp. 1-2 located at
http://www.technovelgy.com/ct/Science-Fiction-News.asp?NewsNum=46;
Ananthaswamy "First robot moved by muscle power" (2004), pp. 1-3;
New Scientist; located at
http://www.newscientist.com/article.ns?id=dn4714; and Freitas
"8.2.1.2 Arteriovenous Microcirculation"; "9.4.3.5 Legged
Ambulation"; "9.4.3.6 Tank-Tread Rolling"; "9.4.3.7 Amoeboid
Locomotion"; "9.4.3.8 Inchworm Locomotion"; "Nanomedicine Volume I:
Basic Capabilities" (1999) pp. 211-214, pp. 316-318; Landes
Bioscience; Georgetown, Tex., USA.
[0111] One or more motive source 150 may include, but is not
limited to, one or more propelling mechanisms such as one or more
cilium-like structures (see, e.g., U.S. Patent Application
2004/0008853; Mathieu, et al. "MRI Systems as a Mean of Propulsion
for a Microdevice in Blood Vessels" (2003) pp. 3419-3422, IEEE; Lu,
et al. "Preliminary Investigation of Bio-carriers Using
Magnetotactic Bacteria"; Proceedings of the 28th IEEE EMBS Annual
International Conference (2006); pp. 3415-3418 IEEE, and Martel
"Towards MRI-Controlled Ferromagnetic and MC-1 Magnetotactic
Bacterial Carriers for Targeted Therapies in Arteriolocapillar
Networks Stimulated by Tumoral Angiogenesis" Proceedings of the
28th IEEE EMBS Annual International Conference (2006) pp. 3399-3402
IEEE.
[0112] One or more motive source 150 may include propelling
mechanisms such as, but not limited to, rollers or wheel-like
structures (see, e.g., U.S. Pat. No. 7,042,184 and U.S. Patent
Application 2006/0119304; screw-like structures (see, e.g.,
Ikeuchi, et al. "Locomotion of Medical Micro Robot with Spiral Ribs
Using Mucus" Seventh International Symposium on Micro Machine and
Human Science (1996) pp. 217-222 IEEE); and/or appendages capable
of walking motion (see, e.g., U.S. Pat. No. 5,574,347; Shristensen
"Musclebot: Microrobot with a Heart" Technovelgy.com; pp. 1-2;
(2004); located at
http://www.technovelgy.com/ct/Science-Fiction-News.asp?NewsNum=46;
and Martel "Fundamentals of high-speed piezo-actuated three-legged
motion for miniature robots designed for nanometer-scale
operations" pp. 1-8), and others. Appendage-like structures may
intermittently engage the lumen wall and push the structural
element with respect to the lumen wall with a walking-type motion,
or may push against fluid within the lumen in a paddling or
swimming motion. In some embodiments, the propelling mechanism may
drive rotational movement of a lumen-wall-engaging structure with
respect to the structural element, e.g., as in turning of a wheel
or a screw element to propel the structural element through a
lumen.
[0113] One or more motive source 150 may include propelling
mechanisms such as, but not limited to, an inchworm-type propulsion
mechanism with suction mechanisms for engaging a surface (see,
e.g., Patrick, et al. "Improved Traction for a Mobile Robot
Traveling on the Heart", Proceedings of the 28.sup.th IEEE EMBS
Annual International Conference (2006) pp. 339-342 IEEE; Dario, et
al. "A Micro Robotic System for Colonoscopy" Proceedings of the
1997 IEEE International Conference on Robotics and Automation
(1997) pp. 1567-1572 IEEE; and Dongxiang, et al. "An earthworm
based miniature robot for intestinal inspection" Proceedings of
SPIE (2001) 4601:396-400 SPIE).
[0114] One or more motive source 150 may include propelling
mechanisms such as, but not limited to, multiple lumen wall
engaging structures, operating in sequence to alternately engage
and disengage the lumen wall, to produce "peristaltic" motion (see,
e.g., U.S. Pat. No. 6,764,441; U.S. Patent Application
2006/0004395; Mangain, et al. "Development of a Peristaltic
Endoscope" IEEE International Conference on Robotics &
Automation 2002; pp. 1-6;
http://biorobots.cwru.edu/publications/ICRA02_Mangan_Endoscope.pdf;
and Meier, et al. "Development of a compliant device for minimally
invasive surgery" Proceedings of the 28.sup.th IEEE EMBS Annual
International Conference (2006) pp. 331-334 IEEE).
[0115] One or more motive source 150 may include propelling
mechanisms such as, but not limited to, one or more paddles,
propellers, or the like, which push against fluid contained within
the lumen rather than engaging the wall of the body lumen (see,
e.g., U.S. Pat. No. 6,240,312; and Behkam, et al. Proceedings of
the 28.sup.th IEEE EMBS Annual International Conference (2006) pp.
2421-2424 IEEE.
[0116] One or more motive source 150 may include mechanisms
configured to allow affixation to a lumen wall or other interior
location, either permanent or temporary. In illustrative
embodiments, configurations for affixing may include, but are not
limited to, one or more anchors configured to attach at least
temporarily to a wall of the lumen, one or more hooks and/or claws,
one or more adhesive materials and/or glues, one or more brakes to
oppose the action of the propelling mechanism, one or more
expanding elements, one or more suction-generating elements, and/or
or a shutoff for the propelling mechanism and/or for one or more
power source 140.
[0117] In some embodiments, one or more configurations for affixing
one or more devices may be activated responsive to control
circuitry. In some embodiments, one or more configurations for
affixing one or more devices may be fixed or movable. Movable
structures may include, but are not limited to, mechanical elements
and/or materials that change shape or rigidity in response to
temperature, electric field, magnetic field, or various other
control signals. Affixation may be permanent, for extended periods,
and/or temporary. As used herein, the term "extended periods" may
include weeks to months to years and subsets thereof. As used
herein, the term "temporary" may include seconds, to minutes, to
hours, to days and subsets thereof.
[0118] One or more motive source 150 may include mechanisms
configured to allow one or more device to become stationary
relative to a flow of fluid through a lumen and/or an internal
location. In illustrative embodiments, configurations for becoming
stationary include, but are not limited to, becoming affixed to a
lumen or other internal location (e.g. by one or more mechanism
described above), and/or reversing the propelling mechanism.
Illustrative embodiments of configurations for reversing a
propelling mechanism include, but are not limited to, reverse
orientation of one or more motive source 150 (e.g. oriented to
provide motive force in a reverse direction, such as against the
flow of fluid, for example), one or more motive source 150
configured to allow bi-directional orientation (e.g. provide motive
force in two directions, optionally 180 degrees apart (in
opposition)), and/or one or more motive source configured to allow
motive force to be applied in variable orientations.
[0119] In one aspect, the disclosure is drawn to one or more
methods for ablating one or more targets optionally at least
partially based on a fluorescent response, optionally using one or
more apparatus 100 and/or 500 and/or device 200, 300 and/or 400
described herein. Although one or more methods may be presented
separately herein, it is intended and envisioned that one or more
methods and/or embodiments of one or more methods may be combined
and/or substituted to encompass the full disclosure. In some
embodiments, one or more methods may include one or more
operations, and be implemented using one or more computing devices
and/or systems.
[0120] In some embodiments, one or more methods of treatment
include providing to a lesion electromagnetic energy selected to
induce a fluorescent response from a target area; detecting the
fluorescent response; identifying the target area at least
partially based on an analysis of the detected fluorescent
response; and providing energy to at least partially ablate the
identified target area in real time. In some embodiments, one or
more methods for ablating one or more target cells include
providing to a lesion electromagnetic energy selected to induce a
fluorescent response from a target area; detecting the fluorescent
response; identifying the target area at least partially based on
an analysis of the detected fluorescent response; and providing
energy to at least partially ablate the identified target area in
real time.
[0121] In some embodiments, one or more methods for detecting and
ablating a target area include providing an untethered device to a
lumen of a subject; providing from the untethered device
electromagnetic energy selected to induce an auto-fluorescent
response in one or more target cells in proximity to the lumen;
detecting the auto-fluorescent response using a sensor in the
untethered device; identifying the target area at least partially
based on an analysis of the detected auto-fluorescent response; and
providing from the untethered device energy configured to at least
partially ablate the identified target area. In some embodiments,
one or more methods of treatment include providing an untethered
device to a lumen of a subject; providing from the untethered
device electromagnetic energy selected to induce an
auto-fluorescent response in one or more target cells in the lumen;
detecting the auto-fluorescent response using a sensor in the
untethered device; identifying the target area at least partially
based on an analysis of the detected auto-fluorescent response; and
providing from the untethered device electromagnetic energy
configured to at least partially ablate the identified target
area.
[0122] In some embodiments, one or more methods for treating or
ameliorating H. pylori infection include providing to a digestive
tract of a subject an untethered ingestible mass, the untethered
ingestible mass configured for non-uniform movement; and emitting
electromagnetic energy from the untethered ingestible mass in a
manner selected to induce photodynamic cell death in H. pylori. In
some embodiments, one or more methods for ablating H. pylori
include providing to a digestive tract of a subject an untethered
ingestible mass, the untethered ingestible mass configured for
non-uniform movement; and emitting electromagnetic energy from the
untethered ingestible mass in a manner selected to induce
photodynamic cell death in H. pylori.
[0123] In some embodiments, one or more methods for detecting and
ablating a target area in a digestive tract include providing to a
subject an optionally rotating untethered ingestible mass and/or
optionally configured for non-uniform movement; providing from the
untethered ingestible mass electromagnetic energy selected to
induce an auto-fluorescent response in one or more target cells in
the digestive tract; detecting the auto-fluorescent response using
a sensor in the untethered device; identifying the target area at
least partially based on an analysis of the detected
auto-fluorescent response; and providing from the untethered device
electromagnetic energy configured to at least partially ablate the
identified target area. In some embodiments, one or more methods
for treating a disease or disorder in a digestive tract include
providing to a subject a rotating untethered ingestible mass;
providing from the untethered ingestible mass electromagnetic
energy selected to induce an auto-fluorescent response in one or
more target cells in the digestive tract; detecting the
auto-fluorescent response using a sensor in the untethered device;
identifying the target area at least partially based on an analysis
of the detected auto-fluorescent response; and providing from the
untethered device electromagnetic energy configured to at least
partially ablate the identified target area. In some embodiments,
one or more methods of treatment include providing to a subject a
rotating untethered ingestible mass; providing from the untethered
ingestible mass electromagnetic energy selected to induce an
auto-fluorescent response in one or more target cells in the
digestive tract; detecting the auto-fluorescent response using a
sensor in the untethered device; identifying the target area at
least partially based on an analysis of the detected
auto-fluorescent response; and providing from the untethered device
electromagnetic energy configured to at least partially ablate the
identified target area.
[0124] In some embodiments, one or more methods for detecting and
ablating one or more target cells include providing to an internal
location a tethered device; providing from the tethered device
electromagnetic energy selected to induce an auto-fluorescent
response from the one or more target cells; detecting the
auto-fluorescent response; identifying a target area at least
partially based on an analysis of the detected auto-fluorescent
response; and providing energy to at least partially ablate the
identified target area in real time. In some embodiments, one or
more methods of treatment include providing to an internal location
a tethered device; providing from the tethered device
electromagnetic energy selected to induce an auto-fluorescent
response from one or more target cells; detecting the
auto-fluorescent response; identifying a target area at least
partially based on an analysis of the detected auto-fluorescent
response; and providing energy to at least partially ablate the
identified target area in real time.
[0125] Embodiments of one or more methods include affixing one or
more devices 200, 300, and/or 400 to a location in a lumen and/or
an interior location. As used herein, the term "affixing" may
include, but is not limited to one or more processes by which the
one or more devices may be held stationary in the lumen or internal
location. The affixation may be temporary and/or permanent as
described herein. Mechanisms by which one or more device may become
affixed are known in the art and/or described herein.
[0126] Embodiments of one or more methods include moving one or
more devices 200, 300, and/or 400 from one location to another
within a lumen and/or internal location. As used herein, the term
"moving" may include, but is not limited to, one or more processes
by which a device may traverse a lumen and or internal location in
one or more directions. Movement may be with the flow of an
optional moving fluid (and/or gravity), against the flow of an
optional moving fluid (and/or gravity), and or at an angle oblique
to a moving flow of fluid (and/or gravity). Movement may be
irrespective of the presence and/or absence of fluid and/or moving
fluid. Movement may be temporary, intermittent, and/or continuous.
Movement may be random and/or non-uniform. Movement may be
controlled by control circuitry, either internal or external to the
device. Movement may be associated with identification and/or
ablation of a target. Mechanisms for moving one or more device are
known in the art and/or are described herein.
[0127] In illustrative embodiments, moving an untethered device
includes moving an untethered device by providing a motive force to
the untethered device. As used herein, the term "motive force" may
include, but is not limited to, a mechanism that allows the
untethered device to move within a lumen and/or internal location,
such as for example, those described for a motive source and a
power source herein. In some embodiments, a motive force is
responsive to control circuitry, is remote-controlled, is
programmable, and/or is feedback-controlled. In some embodiments, a
motive force is powered by a battery, a capacitor, receives power
from one or more external sources, and/or from one or more
physiological sources. In some embodiments, a motive force is
responsible for the randon and or non-uniform movement of a
device.
[0128] Embodiments of one or more methods include providing
electromagnetic energy, optionally optical energy, to a target,
target area, target cell, target tissue, lesion, incision, wound,
internal location, and/or lumen, optionally selected to induce a
fluorescent response. Providing electromagnetic energy optionally
includes using a laser, optionally handheld, or other device to
provide optical energy to a target.
[0129] Parameters associated with the selection of electromagnetic
energy to induce a fluorescent response include, but are not
limited to, the target, the environment associated with the target,
the characteristics of the electromagnetic energy source, and/or
the characteristics of the sensor.
[0130] The parameters associated with the target include, but are
not limited to, the distance of the target from the electromagnetic
source, the depth of the target beneath a surface (e.g. a lumen
wall, an internal surface, a lesion surface), the inherent
fluorescence of the target, the markers/tags used to identify the
target, the size of the target, and/or the movement of the target
(e.g. stationary, steady movement, variable movement, predictable
movement, etc.).
[0131] The parameters associated with the environment include, but
are not limited to, location (e.g. external, internal, lumen,
wound, incision, etc.), milieu (e.g. fluid-filled, air-filled,
blood, digestive contents, etc.), movement (e.g. stationary, steady
movement, intermittent movement, predictable movement, etc.),
physiologic parameters (e.g. pH, temperature, etc.), and/or
non-target fluorescence (e.g. background fluorescence, non-specific
fluorescence, intrinsic non-target fluoresce, etc.).
[0132] The parameters associated with the characteristics of the
electromagnetic energy source include, but are not limited to, the
wavelengths available for selection (e.g. single, two-photon,
multiple, extended-spectrum, etc.), the strength of the emitted
electromagnetic energy (e.g. limitations on distance and/or depth,
etc.), the type of output (e.g. pulsed, two-photon, etc.),
directionality (e.g. limited, variable, varied, etc.), and/or
spatial parameters (e.g. limited, focused, collimated, etc.).
[0133] The parameters associated with the characteristics of the
sensor include, but are not limited to, the detection limits
associated with wavelength (e.g. single, two-photon, multiple,
extended-spectrum, etc.), signal strength (e.g. sensitivity of
detection, level above background, etc.), and/or time (e.g. detects
cumulative readings over time, detects readings at certain time
intervals, or at a certain time post excitation, etc.).
[0134] Embodiments of one or more methods include selecting the
electromagnetic energy, optionally optical energy, to induce the
fluorescent response. Methods for selecting include, but are not
limited, manually, remotely, automatically, programmably,
wirelessly, and/or using control circuitry. Manually selecting
includes, but is not limited to, manually operating one or
mechanism (e.g. a switch, dial, button, etc.) on one or more
apparatus 100 and/or 500, and/or device 200, 300, and/or 400, that
controls the emitted wavelength from one or more electromagnetic
energy source. Remotely selecting includes, but is not limited to,
optionally wirelessly interacting with circuitry on one or more
apparatus 100 and/or 500, and/or device 200, 300, and/or 400 that
controls the wavelength emitted from one or more electromagnetic
energy source. Programmably selecting includes, but is not limited
to, optionally using control circuitry, optionally part of one or
more apparatus 100 and/or 500, and/or device 200, 300, and/or 400
(e.g. internal and/or external), programmed, optionally manually,
remotely, and/or wirelessly, to select the wavelength emitted from
one or more electromagnetic energy source. Methods for programming
control circuitry are well-known to one of skill in the art, and
some applicable control circuitry is described herein.
[0135] Embodiments of one or more methods include monitoring the
electromagnetic energy selected to induce a fluorescent response,
optionally an auto-fluorescent response, optionally a target
fluorescent response, monitoring the energy selected to ablate the
target, optionally electromagnetic energy, optionally particle beam
energy, and/or monitoring the targeting electromagnetic energy,
optionally visual light. Methods of monitoring electromagnetic
energy and/or particle beam energy are known in the art and/or
described herein. Methods include, but are not limited to, using
sensors able to detect one or more characteristics of the
energy.
[0136] Embodiments of one or more methods include detecting a
fluorescent response. Methods of detecting a fluorescent response
include, but are not limited to, detecting a fluorescent response
using one or more sensors, detectors, and/or monitors. Sensors,
detectors, and/or monitors appropriate for detection and/or
monitoring of the fluorescent response are known in the art and/or
described herein. As used herein, the term "detecting" may include
any process by which one or more characteristics of a fluorescent
response may be measured and/or quantified.
[0137] Embodiments of one or more methods include identifying a
target for ablation (e.g. target area, target cells, and/or target
tissues). As used herein, the term "identifying a target" may
include, but is not limited to, processes including selecting a
target and/or determining a target. One or more methods for
identifying a target for ablation optionally include analyzing a
fluorescent response and/or other information, optionally using
control circuitry, optionally in real time.
[0138] Analyzing a fluorescent response to at least partially
identify a target for ablation may include, but is not limited to,
evaluating a fluorescent response at least partially in reference
to baseline fluorescence, background fluorescence, expected
fluorescence, normal fluorescence, reference fluorescence,
non-specific fluorescence, and/or intrinsic non-target
fluorescence, etc. Analyzing a fluorescent response may include,
but is not limited to, subtractively determining a target
fluorescent response (e.g. subtracting the non-target fluorescence
from the total fluorescence to determine the target fluorescence).
Analyzing a fluorescent response may include, but is not limited
to, evaluating a fluorescent response at least partially based on
detection at one or more wavelengths (e.g. single, multiple,
extended-spectrum, etc.), based on time (e.g. one or more times,
time intervals, and/or over time, etc.), based on direction (e.g.
of origination of the emission, etc.), based on strength, and/or
based on distance (e.g. of origination of emission from a sensor).
In illustrative embodiments, analyzing a fluorescent response may
include, but is not limited to, identifying "clumps" and/or
"groups" of autofluorescent cells that in another context might be
considered "normal", but that are not normally grouped and so may
be a target for ablation.
[0139] In illustrative embodiments, an analyzed target fluorescent
response is used to determine the direction from which the response
originated in order to provide ablation energy to the location
and/or general area. In illustrative embodiments, an analyzed
target fluorescent response is used to determine the coordinates
from which the response originated in order to provide ablation
energy to the location and/or general area.
[0140] As used herein, the term "location" may include, but is not
limited to, one or more of a direction, an area, a depth, a site,
or a size, etc. A location may be defined by spatial coordinates
and/or temporal coordinates. A location may be defined as precisely
as the cellular level, for example, or as broadly as a general
area, or a general direction. Methods of determining a location
based on the detection of a fluorescent response are known in the
art and/or described herein. In illustrative embodiments, a target
location may be the cancerous and/or pre-cancerous cells remaining
in a surgical margin. In illustrative embodiments, a target
location may be the microbial cell contamination remaining in a
wound following a sterile wash. In illustrative embodiments, a
target location may be the lumen of a blood vessel following
detection of a target fluorescent response. In illustrative
embodiments, a target location may be the lumen of the digestive
tract in a area with an acidic pH.
[0141] Analyzing other information to at least partially identify a
target for ablation may include, but is not limited to, analyzing
information optionally provided by one or more sensors (e.g.
intrinsic and/or extrinsic to one or more device and/or apparatus)
and/or provided by one or more external sources (e.g. remotely
and/or wirelessly, etc.). Analyzing information optionally provided
by one or more sensors may include analyzing information including,
but not limited to, environmental information such as, but not
limited to, pH, temperature, pressure, chemistry, physiological
measurements, dietary measurements, biological measurements, etc.
In illustrative embodiments, identifying a target fluorescent
response is a least partially based on identifying the pH of the
environment, optionally detecting an acidic pH. Analyzing
information optionally provided by one or more external sources may
include analyzing information including, but not limited to,
environmental information and/or medical and/or veterinary
professional information.
[0142] Analyzing a fluorescent response to at least partially
identify a target for ablation may include, but is not limited to,
evaluating a fluorescent response in real time. As used herein, the
term "in real time" may include, but is not limited to, immediate,
rapid, not requiring operator intervention, automatic, and/or
programmed. In real time may include, but is not limited to,
measurements in femtoseconds, picoseconds, nanoseconds,
milliseconds, as well as longer, and optionally shorter, time
intervals. In illustrative embodiments, analysis in real time is
sufficiently rapid such that the target and the device have not
moved and/or changed positions/locations significantly with respect
to each other. In illustrative embodiments, a fluorescent response
is detected and analyzed, and a target is identified without
operator intervention and the target ablation information is
provided to an energy source.
[0143] Embodiments of one or more methods include providing energy
to at least partially ablate a target. One or more methods include
providing energy to at least partially ablate a target in real
time. As used herein the term "ablation or ablate" may include, but
is not limited to, processes including destroying, modifying,
removing, and/or eliminating, in part or in whole, a target and/or
a material of interest. As used herein, ablation may include the
process of removing material, optionally from a surface, by
irradiating it, optionally with a laser beam. At low laser flux,
the material is heated by the absorbed laser energy and evaporates
or sublimes. At high laser flux, the material is typically
converted to a plasma. Ablation may include the process of removing
material with a pulsed laser, or a continuous wave laser.
[0144] Energy for ablation may include, but is not limited to,
electromagnetic energy, X-ray energy, and particle beam energy.
Electromagnetic energy such as light may cause, for example, a
photoreaction, molecular bond breakage, heating, or other
appropriate effect. Electromagnetic energy sources may include, but
are not limited to, light sources such as light emitting diodes and
laser diodes, or sources of other frequencies of electromagnetic
energy, radio waves, microwaves, ultraviolet rays, infra-red rays,
optical rays, terahertz beams, and the like.
[0145] As used herein, the term "at least partially ablate" may
include partially and/or completely ablating a target. As used
herein, the term "completely ablate" may include ablation of a
target up to the applicable limits of detection (e.g. no longer
detectable by the sensors used to detect the fluorescent response,
no longer detectable over background, and/or no longer
statistically significant). As used herein the term "partially
ablate" may include ablation less than complete ablation, but where
at least some detectable ablation occurs. At least some detection
ablation includes, but is not limited to, ablation detectable by
the sensors used to detect the fluorescent response, statistically
significant ablation, detection by external sensors, and/or
detection by inference from other measurements and/or sensor
readouts.
[0146] Embodiments of one or more methods include providing
targeting electromagnetic energy to a lesion, a lumen, an internal
location, etc. methods for providing targeting electromagnetic
energy are known in the art, and/or described herein. Targeting
electromagnetic energy is optionally optical energy, optionally
visible to the human eye. Targeting electromagnetic energy is
optionally alignable with electromagnetic energy emitted to induce
a fluorescent response and/or with energy emitted to at least
partially ablate a target. In illustrative embodiments, targeting
electromagnetic energy is aligned with the output from one or more
energy sources as a visual aid to a medical and/or veterinary
professional during treatment of a subject.
EXAMPLES
[0147] The following Examples are provided to illustrate, not to
limit, aspects of the present invention. Materials and reagents
described in the Examples are commercially available unless
otherwise specified.
Example 1
Detection and Ablation of Pathogens Prior to Closing a Surgical
Incision
[0148] A surgical incision is screened with a device that detects
and ablates pathogens within the open lesion prior to closing to
prevent postoperative infection. The device emits electromagnetic
energy at wavelengths sufficient to induce autofluorescence of
pathogens within the incision. The device detects the
autofluorescence associated with the pathogens, and in real time
automatically delivers energy sufficient to at least partially
inactivate or ablate the pathogens. Optionally, the device detects
the autofluorescence, collects and processes the data, and at the
discretion of the surgeon or other medical practitioner (or
veterinarian), a trigger mechanism, for example, is used to deliver
energy sufficient to at least partially inactivate or ablate the
pathogens at the coordinates associated with the autofluorescence.
The device may be handheld, for example, and either self-contained
or connected wirelessly or by wire to optionally a power supply,
energy sources, control circuitry, and/or monitor. Alternatively,
the device may be a fixed component of the surgical theater.
[0149] A pathogen or pathogens may be detected at the site of
incision based on autofluorescence induced, for example, by
electromagnetic energy. Naturally occurring autofluorescence in
bacteria, for example, is derived from biomolecules containing
fluorophores, such as porphyrins, amino acids tryptophan, tyrosine,
and phenylalanine, and the coenzymes NADP, NADPH, and flavins
(Koenig, et al. (1994) J. Fluoresc. 4:17-40; Kim, et al. (2004)
IEEE/EMB Magazine January/February 122-129). The excitation maxima
of these biomolecules lie in the range of 250-450 nm (spanning the
ultraviolet/visible (UV/VIS) spectral range), whereas their
emission maxima lie in the range of 280-540 (spanning the UVNIS
spectral range; Ammor (2007) J. Fluoresc. published on-line ahead
of publication).
[0150] For example, two clinically important bacteria, Enterococcus
faecalis, and Staphylococcus aureus, may be differentiated based on
their respective autofluorescence in response to excitation spectra
of 330-510 nm and emission spectra of 410-430 nm (Ammor (2007) J.
Fluoresc. published on-line ahead of publication). Similarly,
Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus
influenzae may be detected using fluorescence spectroscopy at
excitation wavelengths of 250 and 550 nm and emission wavelengths
of 265 and 700 nm (Ammor (2007) J. Fluoresc. published on-line
ahead of publication). Bacteria associated with community acquired
pneumonia, Legionella anisa and Legionella dumoffii, autofluoresce
blue-white when exposed to long-wave (365-nm) UV light (Thacker, et
al. (1990) J. Clin. Microbiol. 28:122-123). Bacillus spores will
autofluoresce when excited by UV irradiation at a wavelength of 352
nm (Laflamme, et al. (2006) J. Fluoresc. 16:733-737). Clostridium
sporogenes, Pseuodomonas aeruginose, Pseudomonas fluorescens,
Kocuria rhizophila, Bacteroides vulgatis, Serratia marcescens, and
Burkholderia cepacia emit yellow-green fluorescent signal when
illuminated with blue light (Sage, et al. (2006) American
Biotechnology Laboratory 24:20-23).
[0151] Autofluorescence of endogenous porphyrins may also be used
to detect bacteria. A number of bacteria produce protoporphyrins,
including Propinibacterium acnes, Bacillus thuringiensis,
Staphylococcus aureus, and some strains of Clostridium,
Bifidobacterium, and Actinomyces (Koenig, et al. (1994) J.
Fluoresc. 4:17-40). Bacteria may also be detected using
fluorescence lifetimes measured at 430, 487, and 514 nm after
selective excitation at 340, 405, and 430 nm (Bouchard, et al.
(2006) J. Biomed. Opt. 11:014011, 1-7).
[0152] Autofluorescence may also be used to detect members of the
fungi family. For example, Candida albicans irradiated with
electromagnetic energy at wavelengths of 465-495 nm autofluoresces
at an emission wavelength of 515-555 nm (Mateus, et al. (2004)
Antimicrob. Agents and Chemother. (2004) 48:3358-3336; Graham
(1983) Am. J. Clin. Pathol. 79:231-234). Similarly, Aspergillus
niger and Aspergillus versicolor may be detected using
autofluorescence in response to excitation at 450-490 nm and
emission at 560 nm (Sage, et al. (2006) American Biotechnology
Laboratory 24:20-23; Graham (1983) Am. J. Clin. Pathol.
79:231-234).
[0153] A pathogen or pathogens at the site of incision may be
inactivated or killed by energy emitted from a device in response
to detection of the pathogen by autofluorescence using the same
device. Many pathogens are inactivated or killed by UV germicidal
irradiation (Anderson, et al. (2000) IEEE Transactions on Plasma
Science 28:83-88; Hancock, et al. (2004) IEEE Transactions on
Plasma Science 32:2026-2031). UV light ranges from UVA (400-315
nm), also called long wave or `blacklight`; UVB (315-280 nm), also
called medium wave; and UVC (<280 nm), also called short wave or
`germicidal`."
[0154] Optionally, a wavelength may be used that completely or
partially inactivates pathogens but limits damage to surrounding
tissue. For example, a wavelength of 630 nm partially inhibits
growth of Pseudomonas aeruginosa and Escherichia coli (Nussbaum, et
al. (2002) J. Clin. Laser Med. Surg. 20:325-333). Similarly, a
number of oral bacteria, including Acinobacillus
actinomycetemcomitans, Fusobacterium nucleatum, Porphromonas
gingivalis, Pnevotella intermedia, and Streptococcus sanguis, may
be partially inactivated using a diode 665 laser at 100 mW for 30 s
(energy density 10.6 J/cm.sup.2) or 60 s (energy density 21.2
J/cm.sup.2) at a distance of 5 mm (Chan, et al. (2003) Lasers Surg.
Med. 18:51-55).
[0155] Inactivation of bacteria by a diode 665 laser may be
enhanced, for example, by pre-staining the bacteria with methylene
blue (Chan, et al. (2003) Lasers Surg. Med. 18:51-55). Similarly,
oral bacteria may be inactivated using a He--Ne laser at 30 mW for
30 s (energy density 3.2 J/cm.sup.2) or 60 s (energy density 6.4
J/cm.sup.2) in combination with methylene blue (Chan, et al. (2003)
Lasers Surg. Med. 18:51-55).
[0156] Alternatively, a pathogen or pathogens may be inactivated or
killed at the incision site with a form of laser thermal ablation
using, for example, a CO.sub.2 or Nd:YAG laser (Bartels, et al.
SPIE Vol 2395:602-606). For example, Staphylococcus aureus may be
partially inactivated or killed using high-power Nd:YAG laser
radiation between 50 and 300 W with laser pulse frequencies of 5 to
30 Hz and pulse energies from 2 to 30 J, resulting in a range of
energy densities from 800 to 270 J/cm.sup.2 (Yeo, et al. (1998)
Pure Appl. Opt. 7:643-655). Escherichia coli 0157:H7, for example,
is extremely sensitive to heat with a maximum tolerance of
approximately 35 degrees centigrade (U.S. Pat. No. 6,030,653).
[0157] Pathogens may be inactivated or killed using X-ray and gamma
electromagnetic energy. For example, Escherichia coli 0157:H7,
Salmonella, and Campylobacter jejuni may be at least partially
inactivated or killed using cobalt-60 gamma radiation at doses of
0.5 to 3 kGy (Clavero, et al. (1994) Applied Environ. Microbiol.
60:2069-2075).
[0158] Alternatively, pathogens may be inactivated or killed using
a form of particle beam irradiation. For example, Salmonella,
Yersinia, and Campylobacter may be at least partially ablated using
accelerated electrons with doses of irradiation ranging from 1-3
kGy (Sarjeant, et al. (2005) Poult. Sci. 84:955-958). Similarly,
Bacillus endospores may be at least partially ablated using
electron beam irradiation with doses ranging from 5 to 40 kGy
(Helfinstine, et al. (2005) Applied Environ. Microbiol.
71:7029-7032).
[0159] Viruses may be inactivated on a surface using UV irradiation
(Tseng & Li, (2007) J. Occup. Envirn. Hyg. 4:400-405). Fungi,
for example Aspergillus flavus and Aspergillus fumigatus, may also
be inactivated using UV germicidal irradiation at 12-98 mJ/cm.sup.2
(Green, et al. (2004) Can. J. Microbiol. 50:221-224).
[0160] Alternatively, energy may be used that disrupts the function
of heme iron porphyrins associated with iron uptake and
utilization, inactivating iron dependent bacteria such as
Escherichia coli and Salmonella (U.S. Pat. No. 6,030,653).
Pathogens may be inactivated by irradiating the surface with
visible and near infrared light having wavelengths of approximately
465 nm, 600 nm, and 950 nm, respectively.
[0161] In some instances, the entirety of the affected tissue may
be irradiated to at least partially inactivate or kill pathogens.
Alternatively, focused energy may be directed only to those sites
emitting pathogen-associated autofluorescence or fluorescence. A
pathogen or pathogens at the site of incision may be inactivated or
killed by energy emitted from a device in either the presence or
absence of prophylactic antibiotics (Dellinger, et al. (1994) Clin.
Infect. Dis. 18:422-427).
[0162] There are a number of microbial pathogens of concern during
surgical treatment that may lead to difficult to treat nosocomial
or hospital acquired infection, including methicillin-resistant
Staphylococcus aureus (MRSA), Staphylococcus epidermidis,
Streptococcus pyogenes, Pseudomonas aeruginosa,
vancomycin-resistant Enterococci (VRE), extended spectrum
b-lactamase-producing bacteria (ESBL), multi-drug resistance in
Mycobacterium tuberculosis (MDRTB) strains as well as multi-drug
resistant Gram-negative bacteria (Lichtenstern, et al. (2007) Dig.
Surg. 24:1-11; NIAID (National Institute of Allergy and Infectious
Disease) Profile Fiscal Year 2005, Selected Scientific Areas of
Research, Antimicrobial Resistance, pages 52-55).
[0163] The Gram-positive bacteria Staphylococcus aureus is a common
cause of superficial skin infections such as boils, furuncles,
styes, impetigo. S. aureus is also a major cause of nosocomial and
community-acquired infections, particularly in individuals
debilitated by chronic illness, traumatic injury, burns or
immunosuppression, as well as a common cause of postoperative
infection. The infection may produce abscesses at the stitches or
may cause extensive destruction of the incision site. Postoperative
infections caused by S. aureus may appear a few days to several
weeks after an operation but may develop more slowly in an
individual taking antibiotics. Upon bloodstream dissemination or by
continuous spread, S. aureus can readily survive in various deep
tissues and can cause, among others, abscess formation,
osteomyelitis, endocarditis, and sepsis. S. aureus may be detected
by autofluorescence at the incision site using a device emitting
electromagnetic energy at a wavelength, for example, of 488 nm
(Hilton (1998) SPIE 3491:1174-1178). Optionally, S. aureus may be
distinguished from, for example, Escherichia coli and Enterococcus
faecalis based on emission spectra induced by excitations at
410-430 nm (Giana, et al. (2003) J. Fluoresc. 13:489-493; Ammor
(2007) J. Fluoresc. published on-line ahead of publication).
[0164] S. aureus associated with the incision site may be killed or
inactivated by irradiating the tissue with energy, for example, at
a short UV "germicidal" wavelength as described above.
Alternatively, S. aureus may be inactivated using a blue light with
a wavelength, for example, of 405 nm at doses ranging from 1-20
Jcm.sup.-2 (Guffey, et al. (2006) Photomed. Laser Surg.
24:680-683). Optionally, a blue light may be combined, for example,
with an infrared light at a wavelength of 880 nm to promote tissue
repair in combination with bacterial ablation (Guffey, et al.
(2006) Photomed. Laser Surg. 24:680-683). In some instances, the
entirety of the effected tissue may be irradiated. Alternatively,
focused energy may be directed only to those sites emitting S.
aureus-associated autofluorescence.
[0165] The Gram-negative bacteria Pseudomonas aeruginosa is another
common cause of nosocomial infections, particularly in patients
hospitalized with cancer, cystic fibrosis, and burns, and has a
mortality rate of 50%. Other infections caused by Pseudomonas
species include endocarditis, pneumonia, and infections of the
urinary tract, central nervous system, wounds, eyes, ears, skin,
and musculoskeletal system. P. aeruginosa is an opportunistic and
ubiquitous pathogen with limited tissue penetration on its own,
gaining entry to the host, for example, through burns, wounds,
intravenous and urinary catheterization, and surgical procedures.
P. aeruginosa may be detected by autofluorescence at the incision
site using a device emitting electromagnetic energy at a
wavelength, for example, of 488 nm (Hilton (1998) SPIE
3491:1174-1178). P. aeruginosa contains a pigment called pyocyanin
which appears blue in visible light and may also be used for
detection.
[0166] P. aeruginosa may be killed using a blue light with a
wavelength, for example, of 405 nm at doses ranging from 1-20
Jcm.sup.2 (Guffey, et al. (2006) Photomed. Laser Surg. 24:680-683).
Alternatively, irradiation using a wavelength, for example, of 630
nm at 1-20 Jcm.sup.-2 may partially inactivate P. aeruginosa
(Nussbaum, et al. (2002) J. Clin. Laser Med. Surg. 20:325-333).
Example 2
Detection and Ablation of Pathogens Prior to Closing and/or
Bandaging a Wound
[0167] A wound may be screened with a handheld device that detects
and ablates pathogens within the open lesion prior to closing (e.g.
suturing) and/or bandaging to prevent possible microbial infection.
The device emits electromagnetic energy at wavelengths sufficient
to induce autofluorescence of pathogens within the wound.
Alternatively, the device emits electromagnetic energy at
wavelengths sufficient to induce fluorescence of reagents applied
to the wound to selectively detect pathogens, such as, for example,
a chemical dye or an antibody or aptamer conjugated to a
fluorescent tag. Pathogens may include bacteria, fungi and/or
viruses. The handheld device detects the autofluorescence or
reagent-induced fluorescence associated with the pathogens and in
real time automatically delivers energy sufficient to ablate or
kill the pathogens. Optionally, the handheld device detects the
autofluorescence, collects and processes the data, and at the
discretion of the user, a trigger mechanism, for example, is used
to deliver energy sufficient to at least partially inactivate or
ablate the pathogens at the coordinates associated with the
autofluorescence.
[0168] Pathogens commonly associated with wound infections include
the Gram-positive cocci Streptococcus pyogenes, Enterococcus
faecalis, and Staphylococcus aureus, the Gram-negative rods
Pseudomonas aeruginosa, Enterobacter species, Escherichia coli,
Klebsiella species, and Proteus species, the anaerobes Bacteroides
and Clostridium, and the fungi Candida and Aspergillus (World Wide
Wounds January 2004). Additional microbes of concern include
Burcella, which infects cows, sheep, and goats, and can be
transmitted through secretion and excretion to open wounds,
Bartonella henselae, which is associated with cats and can cause
"cat scratch fever", and Clostridium tetani which survives for
years in soil and animal feces and can cause infection in both
superficial wounds and deep in contaminated wounds of individuals
not immunized against tetanus (Park, et al. (2001) J. Bacteriol.
183:5751-5755). In addition, Vibrio vulnificus is an emerging human
pathogen which is found primarily in sea water and can be
transmitted into open wounds and cause infection (Oliver, et al.
(1986) Applied Environmental Microbiology 52:1209-1211). Among
healthy individuals, ingestion of V. vulnificus can cause vomiting,
diarrhea, and abdominal pain. In immunocompromised persons,
particularly those with chronic liver disease, V. vulnificus can
invade the bloodstream through a wound, causing primary septicemia
and a 50% mortality rate.
[0169] A pathogen or pathogens may be detected at the wound site
based on autofluorescence induced by electromagnetic energy at
specific or multiple wavelengths, as described herein. Bartonella
henselae, for example, has weak autofluorescence at an excitation
wavelength of 485 nm and emission wavelength of 538 nm (Park, et
al. (2001) J. Bacteriol. 183:5751-5755). Some strains of V.
vulnificus exhibit bioluminescence with maximal light emission at
483 nm (Oliver, et al. (1986) Applied Environmental Microbiology
52:1209-1211).
[0170] Alternatively, pathogens may be detected at the wound site
based on addition of an agent or agents that fluoresces and binds
selectively to the pathogen, allowing for detection and subsequent
ablation of the pathogen. For example, a fluorescent stain such as
BacLight.TM. Green or BacLight.TM. Red bacterial stain
(absorption/emission: 480/516 and 581/644, respectively) may be
used to detect, for example, Staphylococcus aureus and Escherichia
coli (Invitrogen, Carlsbad, Calif.). S. aureus may also be detected
at the wound site based on binding of immunoglobulins to the
bacterial cell wall. Protein A on the surface of S. aureus readily
binds the IgG class of immunoglobulins (Hjelm, et al. (1972) FEBS
Lett. 28:73-76). To detect S. aureus, the incision site may be
briefly sprayed with a sterile saline solution containing, for
example, an IgG antibody conjugated to a fluorescent tag, for
example FITC, Rhodamine, or Cy3, and rinsed. The fluorescence is
detected by the handheld device. In response, energy is emitted
specifically to the fluorescing site and the bacteria are
killed.
[0171] Alternatively, pathogens may be detected at the wound site
using fluorescently labeled antibodies. For example, Streptococcus
pyogenses, one of the main pathogens associated with necrotizing
fasciitis, may be detected using antibodies from commercial sources
(e.g. AbD SEROTEC, Oxford, UK; Affinity BioReagents, Golden, Colo.;
GeneTex, Inc. San Antonio, Tex.). Antibodies against S. pyogenses
may be conjugated, for example, with a fluorescent tag such as the
Alexa Fluors, FITC, Oregon Green, Texas Red, Rhodamine, Pacific
Blue, Pacific Orange, Cy3, or Cy5 using labeling kits available
from commercial sources (e.g. Invitrogen, Carlsbad, Calif.; Pierce,
Rockford, Ill.). Alternatively, antibodies to S. pyogenses may be
labeled with quantum dot nanocrystals using labeling kits from
commercial sources (e.g. Invitrogen, Carlsbad, Calif.). Similarly,
P. aeruginosa and S. aureus, for example, may be detected at the
wound site using commercially available antibodies tagged with a
fluorophore (e.g. Accurate Chemical & Scientific Co., Westbury,
N.Y.; AbD SEROTEC, Oxford, UK; Cell Sciences Inc., Canton,
Mass.).
[0172] The fluorescing bacterial stain, immunoglobulin, antibody,
or aptamer may be administered to the wound in a sterile solution,
rinsed and the wound subsequently screened with the handheld
device. The handheld device may be placed in close proximity to a
wound and emits electromagnetic energy at wavelengths ranging, for
example, from 300 to 700 nm to excite autofluorescence of
endogenous molecules or fluorescence of a probe associated with the
pathogen. The resulting fluorescence is detected by the handheld
device which subsequently emits energy sufficient to at least
partially inactivate or ablate the pathogen. In some instances, the
entirety of the effected tissue may be irradiated. Alternatively,
focused energy may be directed only to those sites emitting
pathogen-associated autofluorescence or fluorescence.
[0173] Autofluorescence may also be used to detect members of the
fungi family. For example, Candida albicans irradiated with
electromagnetic energy at wavelengths of 465-495 nm autofluoresces
at an emission wavelength of 515-555 nm (Mateus, et al. (2004)
Antimicrobial Agents and Chemotherapy 48:3358-3336; Graham (1983)
Am. J. Clin. Pathol. 79:231-234). Similarly, Aspergillus niger and
Aspergillus versicolor may be detected using autofluorescence in
response to excitation at 450-490 nm and emission at 560 nm (Sage,
et al. (2006) American Biotechnology Laboratory 24:20-23; Graham
(1983) Am. J. Clin. Pathol. 79:231-234). Alternatively, fungi may
be detected in a wound using the non-selective dye, Congo Red,
which fluoresces at excitation maxima of 470 and 546 nm when
irradiated with electromagnetic energy at wavelengths ranging from
450-560 nm (Slifkin, et al. (1988) J. Clin. Microbiol.
26:827-830).
[0174] A pathogen or pathogens at the wound site may be inactivated
or killed by energy emitted from a handheld device in response to
detection of the pathogen or pathogens by autofluorescence using
the same handheld device. Energy in the form of UV irradiation may
be used to at least partially inactivate or kill a pathogen or
pathogens as described herein. Alternatively, a pathogen, for
example Escherichia coli, may be at least partially inactivated or
killed at a wound site in response to fluence doses ranging from
130-260 J/cm.sup.2 using a 810 nm diode laser (Jawhara, et al
(2006) Lasers Med. Sci. 21:153-159). Alternatively, a pathogen or
pathogens may be at least partially inactivated or killed at the
wound site with a form of laser thermal ablation using energy
emitted, for example, from a CO.sub.2 (10,600 nm) or a Nd:YAG (1064
nm) laser (Bartels, et al. SPIE Vol 2395:602-606). For example,
Staphylococcus epidermidis, a common skin bacteria, may be killed
using pulsed radiation from a Nd:YAG laser with an exposure of
1000-2000 J/cm.sup.2 (Gronqvist, et al. (2000) Lasers Surg. Med.
27:336-340). Alternatively, a pathogen at a wound site may be at
least partially inactivated or killed using electron beam or x-ray
or gamma irradiation as described herein.
[0175] Optionally, energy emitted from the handheld device may be
combined with a photosensitive agent applied directly to the wound
(Maisch (2007) Lasers Med. Sci. 22:83-91; Joni, et al. (2006)
Lasers Surg. Med. 38:468-481). As such, the photosensitive agent
may be administered to the wound in a sterile solution, allowed to
incubate for a certain interval, for example 1-30 minutes, rinsed
and subsequently screened with the handheld device. The wound may
be irradiated by the handheld device first with wavelengths
sufficient to detect the photosensitive agent and second with
energy sufficient to at least partially inactivate or kill the
pathogens. For example, Staphylococcus aureus and Pseudomonas
aeruginosa may be inactivated using either a 0.95-mW helium-neon
laser (632 nm) or a 5-mW indium-gallium-aluminum-phosphate laser
(670 nm) with exposure doses ranging from 0.1 to 10.0 J/cm.sup.2 in
combination with the bacterial sensitizing agent, toluidine blue O,
(DeSimone, et al. (1999) Phys. Ther. 79:839-846). Alternatively, a
diode laser with an emission wavelength, for example, of 808 nm may
be used in combination with a topically applied fluorescing dye,
for example, indocyanine green (ICG), to inactive a pathogen or
pathogens (Bartels, et al. SPIE Vol 2395:602-606). ICG may be used
to concentrate the diode laser energy to very specific "stained"
areas with minimal damage to surrounding tissue. Optionally, a
polycationic photosensitizer conjugated between, for example,
poly-L-lysine and chlorin.sub..epsilon.6, may be topically applied
to a wound and subsequently irradiated with a diode laser at 665 nm
at doses ranging from, for example, 40-160 J/cm.sup.2 to kill
bacteria (Hamblin, et al. (2002) Photochem. Photobiol. 75:51-57).
Optionally, pathogens in a wound site, such as, for example,
Staphylococcus aureus and Staphylococcus epidermidis, may be at
least partially inactivated using energy from, for example, an
argon-ion pumped dye laser (wavelength of 630 nm with total light
dose of 180 J/cm2) in combination with 5-aminolevulinic acid or
Photofrin (Karrer, et al (1999) Lasers Med. Sci. 14:54-61; Nitzan,
et al (1999) Lasers Med. Sci. 14:269-277).
Example 3
Detection and Ablation of Pathogens on Oral or Skin Surfaces
[0176] An oral cavity or surface of the skin may be screened with a
device that detects and ablates pathogens associated with plaque
and acne, respectively. The device emits electromagnetic energy at
wavelengths sufficient to induce autofluorescence of pathogens on
the surface. Alternatively, the device emits electromagnetic energy
at wavelengths sufficient to cause fluorescence of reagents added
to the surface to selectively detect pathogens, such as, for
example, a chemical dye or an antibody or aptamer conjugated to a
fluorescent tag. Pathogens may include bacteria, fungi and/or
viruses. The device detects the autofluorescence or reagent-induced
fluorescence associated with the pathogens and in real time
automatically delivers energy sufficient to ablate or kill the
pathogens. Optionally, the device detects the autofluorescence,
collects and processes the data, and at the discretion of the
physician or other medical practitioner, a trigger mechanism, for
example, is used to deliver energy sufficient to at least partially
inactivate or ablate the pathogens at the coordinates associated
with the autofluorescence. The device may be handheld, for example,
and either self-contained or connected wirelessly or by wire to
optionally a power supply, energy sources, control circuitry,
and/or monitor. Alternatively, the device may be a fixed component
of, for example, a dentist's or doctor's office.
[0177] A device emitting energy may be used to detect and ablate
the pathogens associated with dental plaque. For example, pathogens
associated with caries and dental plaques, including Actinomyces
odontolyticus, Prevotella intermedia, Porphyromonas gingivalis,
Peptostreptococcus, Candida albicans, and Corynebacterium, all
autofluoresce red in response to violet-blue light at a wavelength
of 405 nm (van der Veen, et al. (2006) Caries Res. 40:542-545;
Koenig, et al. (1994) J. Fluoresc. 4:17-40). Similarly, healthy
dental tissue may be distinguished from carious lesions based on
the autofluorescence of the associated pathogens (Koenig, et al.
(1994) J. Fluoresc. 4:17-40). For example, healthy dental tissue
irradiated with an excitation wavelength, for example, of 405 nm
may exhibit a broad emission spectra in the short-wavelength
portion of the visible spectrum while fluorescence spectra from a
carious lesion may have a maxima in the red spectral region with a
main band at 635 nm, for example (Koenig, et al. (1994) J.
Fluoresc. 4:17-40). Once the autofluorescence is detected, energy
emitted from the device may be used to at least partially
inactivate or kill the fluorescing bacteria in real time using the
methods and/or devices described herein.
[0178] A device emitting energy may be used to detect and ablate
the pathogens associated with acne vulgaris. For example, the
Gram-positive bacteria Propionibacterium acnes, which are involved
in the pathogenesis of acne vulgaris, may be detected on the
surface of the skin using autofluorescence (Koenig, et al. (1994)
J. Fluoresc. 4:17-40; Shalita, et al (2001) SPIE Vol. 4244, p.
61-73). A laser emitting radiation at 407 nm, for example, may be
used to detect fluorescent spots in the nasal area and in pimples
of acne patients. The spots may differ in color, with their
spectrum consisting of three main peaks, at about 580-600, 620, and
640 nm, and may be associated with autofluorescence induced by
endogenous porphyrins such as protoporphyrin and coproporphyrin
(Koenig, et al. (1994) J. Fluoresc. 4:17-40). Once the
autofluorescence is detected, energy emitted from the device, for
example, UV radiation, may be used to at least partially inactivate
or kill the fluorescing bacteria in real time using the methods
described herein. Alternatively, electromagnetic energy emitted
from the device in the violet-blue range (407-420 nm) may be used
to at least partially inactivate or kill pathogens associated with
acne vulgaris by activating the endogenous porphyrins and causing
photo-destructive ablation of the bacteria (Shalita, et al (2001)
SPIE Vol. 4244, p. 61-73). For example, patients with acne vulgaris
may be treated with a 400w UV-free, enhanced blue (407-420 nm)
metal halide lamp producing, for example, 90 mW/cm.sup.2
homogeneous illumination (Shalita, et al (2001) SPIE Vol. 4244, p.
61-73).
[0179] Alternatively, a pathogen in the oral cavity or on the
surface of the skin may be at least partially inactivated or killed
using electron beam or x-ray or gamma irradiation as described
herein.
Example 4
Detection and Ablation of Cancer and Cancer Margins
[0180] Tissue may be screened with a device that detects and
ablates cancerous cells optionally in real time. The device emits
electromagnetic energy at wavelengths to induce autofluorescence
selected to differentiate between normal and cancerous cells.
Alternatively, the device emits electromagnetic energy at
wavelengths sufficient to cause fluorescence of reagents added to
the tissue to selectively detect cancerous cells, such as, for
example, a photosensitizer, a chemical dye, or an antibody or
aptamer conjugated to a fluorescent tag. Autofluorescence or
reagent-induced fluorescence associated with cancerous cells may be
used to detect cancers and to aide in surgical intervention. In
addition, autofluorescence or reagent-induced fluorescence
associated with cancerous cells may be used to aide a medical
practitioner in defining the margins of a solid tumor to ensure
thorough excision of the lesion.
[0181] The device detects the autofluorescence or reagent-induced
fluorescence associated with the cancerous cells and in real time
delivers energy sufficient to at least partially inactivate or
ablate the cancerous cells. Optionally, the device detects the
autofluorescence, collects and processes the data, and at the
discretion of the surgeon or other medical (or veterinary)
practitioner, a trigger mechanism, for example, is used to deliver
energy sufficient to at least partially inactivate or ablate the
cancerous cells at the coordinates associated with the
autofluorescence. The device may be handheld, for example, and
either self-contained or connected wirelessly or by wire to
optionally a power supply, energy sources, control circuitry,
and/or monitor. Alternatively, the device may be a fixed component
of a surgical theater, doctor's office, or other venue for patient
treatment.
[0182] Electromagnetic energy emitted from a device may be used to
induce autofluorescence of a tissue such as, for example, the
surface of the skin or the surface of an internal organ exposed
during surgery. The differences in the properties of emitted
fluorescence may be used to distinguish between normal and
pathological tissue. Tissue may be illuminated with electromagnetic
energy at specific wavelengths of ultraviolet or visible light, for
example. Endogenous fluorophores will absorb the energy and emit it
as fluorescent light at a longer wavelength. Tissue
autofluorescence may originate from aromatic amino acids such as
tryptophan, tyrosine, and phenylalanine (excitation wavelengths of
200-340 nm, emission wavelengths of 360-370, 455 nm), from reduced
pyridine nucleotides such as nicotinamide adenine dinucleotide
(NADH, excitation wavelength of 360 nm, emission wavelength of 460
nm), from flavins and flavin nucleotides such as riboflavin and
flavin mononucleotide (excitation wavelengths of 360 nm, 445-470
nm, emission wavelengths of 440 nm, 520 nm), from structural
proteins such as collagen, and from lipopigments such as ceroid and
lipofuscin (Chung, et al. (2005) Current Surgery 62:365-370;
DaCosta, et al. (2005) J. Clin. Path. 58:766-774).
[0183] Differences in the properties of emitted autofluorescence
may be used to distinguish, for example, between normal and
cancerous cells and tissue in a variety of epithelial organ
systems, including the cervix, colon, bladder, bronchus and oral
mucosa (Ann. Surg. Oncol. (2003) 11:65-70; Weingandt, et al. (2002)
BJOG 109:947-951; DaCosta, et al. (2005) J. Clin. Path. 58:766-775;
Chiyo, et al. (2005) Lung Cancer 48:307-313). For example, changes
in autofluorescence emission (350 to 700 nm) of premalignant or
malignant lesions in the oral cavity relative to normal tissue may
be detected using excitation wavelengths of 337 nm, 365 nm, and 410
nm (Gillenwater, et al. (1998) Arch. Otolaryngol. Head Neck Surg.
124:1251-1258). In this instance, the fluorescence intensity of
normal mucosa may be greater than that of abnormal areas, while the
ratio of red fluorescence (635 nm) to blue fluorescence (455-490
nm) intensities may be greater in abnormal areas. Autofluorescence
may also be used to distinguish between normal and cancerous cells
in non-epithelial organ systems, such as, for example, between
normal white and gray matter and cancerous cells in the brain (U.S.
Pat. No. 6,377,841).
[0184] Alternatively, cancerous cells may be detected using
electromagnetic energy in combination with a light-activated dye.
For example, Photofrin.RTM. (Axcan Pharma, Inc.) administered
systemically to patients with cancer in the oral cavity, esophagus
or bronchus accumulates preferentially in cancerous cells.
Fluorescence of activated Photoftin.RTM. in cancer cells may be
measured at 630 nm, for example, in response to excitation
wavelengths of 405 nm and 506 nm 1-50 hours after administration
(Braichotte, et al. (1995) Cancer 75:2768-2778).
[0185] As cancerous cells are identified based on differences in
autofluorescence relative to normal cells using the device, the
same device may be used in real time to ablate the identified
cancerous cells. A cancerous cell or cells may be ablated by energy
in the form of high-intensity light emitted, for example, by a
laser. Lasers are commonly used to treat superficial cancers, such
as basal cell skin cancer and the very early stages of some
cancers, such as cervical, penile, vaginal, vulvar, and non-small
cell lung cancer (National Cancer Institute (2004) Lasers in Cancer
Treatment FactSheet). Energy emitted from a laser may also be used
to relieve certain symptoms associated with cancer, such as
bleeding or obstruction. For example, a laser may be used to shrink
or destroy a tumor blocking the trachea or the esophagus or to
remove polyps or tumors blocking the colon or stomach.
[0186] A variety of lasers with varied excitation wavelengths and
penetration potential may be used to generate electromagnetic
energy sufficient to ablate a cancer cell or cells (Burr
Interventional Technologies for Tissue Volume Reduction, October
2004). For example, a cancer cell or cells may be ablated using a
CO.sub.2 laser (10,600 nm, 0.1-0.2 mm penetration depth).
Alternatively, cancer cells may be ablated by a
Yttrium-Aluminium-Garnet (YAG) laser with Neodymium (Nd, 1064 nm or
1320 nm, 3-4 mm penetration depth), Erbium (Eb, 2940 nm, with
<0.1 mm penetration depth), or Holmium (Ho, 2070 nm).
Alternatively, cancer cells may be ablated by diode lasers
(600-1600 nm), argon laser (488 nm and 514 nm, 1-1.5 mm penetration
depth), or an excimer laser (180-350 nm, cell/tissue
disintegration). As such, the device may contain one or more of the
lasers described herein as an optical energy source for use in
exciting and/or ablating the target tissue.
[0187] Alternatively, a cancer cell or cells may be ablated by
electromagnetic energy emitted from a laser in combination with a
photosensitizing agent in a process termed photodynamic therapy
(PDT; National Cancer Institute (2004) Lasers in Cancer Treatment
FactSheet). For example, a patient may be injected with a
photosensitizing agent such as, for example, Photofrin or
5-aminolevulinic acid, which after a few days concentrates in the
cancerous cells. Electromagnetic energy from, for example, a laser
is then used to activate the photosensitizing agent which has a
subsequent toxic effect on the cancer cell or cells and results in
cell death.
[0188] Alternatively, a cancer cell or cells may be ablated using
x-ray energy. X-ray therapy or radiotherapy may be used to treat
almost every type of solid tumor, including cancers of the brain,
breast, cervix, larynx, lung, pancreas, prostate, skin, spine,
stomach, uterus, or soft tissue sarcomas (National Cancer Institute
(2004) Radiation Therapy for Cancer FactSheet). As such, the device
may include a standard linear accelerator that emits X-ray
electromagnetic energy at wavelengths sufficient for therapeutic
ablation of cancerous cells. Alternatively, the device may contain
a miniature X-ray emitter (see e.g. U.S. Patent Application
2004/218724 A1). Alternatively, the device may contain
radioisotopes such as cobalt 60, cesium 137, or europium 152, for
example, that emit strong gamma rays and may be used to ablate
cancerous cells. Optionally, the device may contain other
intrinsically radioactive isotope such as those that might be used
for brachytherapy, including, for example, iodine 125, iodine 131,
strontium 89, phosphorous, palladium, or phosphate (National Cancer
Institute (2004) Radiation Therapy for Cancer FactSheet).
[0189] Alternatively, a cancer cell or cells may be ablated by
using particle beam energy generated for example by a betatron,
cyclotron or microton (Podgorsak, Chapter 5). Alternatively,
particle beam energy may be generated using LINAC (linear
accelerator)-based external beam radiotherapy. Medical LINACs
accelerate electrons to kinetic energies from 4 to 25 MeV using
microwave radiofrequency waves at 10.sup.3 to 10.sup.4 MHz
(Podgorsak, Chapter 5). A LINAC may provide X-rays in the low
megavoltage range (4 to 6 MV). Alternatively, a LINAC may provide
both X-rays and electrons at various megavoltage energies, for
example, two photon energies (6 and 18 MV) and several electron
energies (6, 9, 12, 16, and 22 MeV; Podgorsak, Chapter 5).
[0190] Breast cancer may be detected using a device that emits
electromagnetic energy at a wavelength or wavelengths sufficient to
induce autofluorescence of malignant tissue. For example, an
excitation-emission matrix of tissue autofluorescence generated
using incremental excitation and emission wavelengths may be used
to differentiate between normal and malignant breast tissue (Ann.
Surg. Oncol. (2003) 11:65-70). Breast tissue may be irradiated with
electromagnetic energy at excitation wavelengths of 300 to 460 nm,
for example, in 10 to 20 nm increments and the resulting
fluorescence emission recorded in 5 to 10 nm increments beginning
with a wavelength, for example, 10 nm longer than the excitation
wavelength, up to, for example, 600 nm (e.g. 360 to 600 nm for a
350 nm excitation). An excitation-emission matrix may be generated
using this information and changes in peaks and valleys of
fluorescence intensity may be used to distinguish between normal
and malignant tissue. Optionally, a N.sub.2 laser emitting 7 nsec
pulses with a repetition rate of 10 Hz, pulse energy of 200 .mu.J,
and filtered excitation wavelength of 337 nm may be used to
distinguish between autofluorescence of normal and malignant breast
tissue (Gupta, et al. (1997) Lasers Surg. Med. 21:417-422).
Alternatively, cancerous breast tissue may be ablated using X-ray
energy, for example, from a miniature electron beam-driven X-ray
source at doses of 5 to 20 Gy (Ross, et al. (2005) Breast Cancer
Res. 7:110-112). Alternatively, a breast tumor may be at least
partially ablated using electron beam intra-operative radiotherapy
with a radiation dose of 17 to 21 Gy (Ross, et al. (2005) Breast
Cancer Res. 7:110-112).
[0191] Squamous intraepithelial lesions of the cervix may be
differentiated from normal squamous tissue by autofluorescence
using an electromagnetic energy emission wavelength of 460-nm (U.S.
Pat. No. 5,623,932). Alternatively, cervical intraepithelial
neoplasia may be differentiated from normal tissue by
autofluorescence using a frequency tripled Nd:YAG laser with an
excitation wavelength of 355 nm (Nordstrom, et al. (2001) Lasers
Surg. Med. 29:118-127). Under these conditions, normal tissue may
have an autofluorescence maxima (.about.460 nm) that is shifted to
the left relative to neoplastic tissue (.about.470 nm) and is of
higher intensity, allowing for differentiation between normal and
abnormal tissue (Nordstrom, et al. (2001) Lasers Surg. Med.
29:118-127). Optionally, excitation wavelengths between 375 and 440
nm to induce autofluorescence may be used to distinguish between
normal and precancerous lesions of the cervix (Weingandt, et al.
(2002) BJOG 109:947-951). Alternatively, a fluorophore synthesized
in the tissue after administration of a precursor molecule may be
used in combination with electromagnetic energy to detect cancerous
cells, for example, in the cervix (Andrejevic-Blant, et al. (2004)
Lasers Surg. Med. 35:276-283). For example, cervical
intraepithelial neoplasia may be detected by first applying
5-aminolevulinic acid topically to the cervix followed by porphyrin
fluorescence spectroscopy (Keefe, et al. (2002) Lasers Surg. Med.
31:289-293). Cervical cancer may be ablated using laser conization
or vaporization using, for example, a CO.sub.2 laser focused to
spot size of 0.1-0.2 mm with a continuous beam of 40-60 W and a
power density of 80,000-165,000 W/cm2 (Bekassy, et al. (1997)
Lasers Surg. Med. 20:461-466) or a garnet (Nd:YAG) laser.
[0192] The early stages of melanoma may be detected using a device
that emits electromagnetic energy at incremental wavelengths
ranging, for example, from 400-1000 nm using, for example, an
acoustic-optic tunable filter (ACTF) in combination with, for
example, a white light generated with an Kr--Ar laser (Farkas, et
al. (2001) Pigment Cell Res. 14:2-8). Spectral imaging of this sort
may also be accomplished, for example, using rotating interference
filters, the Fabry-Perot interferometer, liquid crystal tunable
filters (LCTF), gratings or prisms, or Fourier transform
spectroscopy (Chung, et al. (2005) Current Surgery 62:365-370). The
reflected light from the potentially cancerous pigmented tissue is
collected at specific wavelengths. A microprocessor may be used to
generate a profile of emission intensity across the electromagnetic
energy spectrum. The resulting profile may be compared with that of
normal pigmented tissue to identify specific areas of dysplasia.
Autofluorescence may also be used to differentiate between normal
skin and non-melanoma skin lesions. For example, autofluorescence
induced by an excitation wavelength of 410 nm may be used to
distinguish between normal tissue, basal cell carcinoma, squamous
cell carcinoma, and actinic keratosis (Panjepour, et al. (2002)
Lasers Surg. Med. 31:367-373). Optionally, autofluorescence may be
used to distinguish between sun-exposed and sun-protected areas of
skin and may also indicate regions of sun damage (Davies, et al.
(2001) Applied Spectroscopy 55:1489-1894). Once the areas of
dysplasia or sun damage are identified, the device may emit in real
time energy sufficient to ablate the abnormal cell or cells. For
example, the lesion may be ablated using a carbon dioxide laser
with a wavelength of 10,600 nm and a power output of 80 W (Gibson,
et al. (2004) Br. J. Surg. 91:893-895).
Example 5
Detection and Ablation of Gastrointestinal Pathogens with an
Untethered Ingestible Device
[0193] An untethered ingestible device may be used to detect and
ablate gastrointestinal pathogens optionally in real time. The
device emits electromagnetic energy at wavelengths sufficient to
induce autofluorescence of pathogens within the gastrointestinal
tract. Alternatively, the device emits electromagnetic energy at
wavelengths sufficient to induce fluorescence of reagents added to
the gastrointestinal tract to selectively detect pathogens, such
as, for example, a chemical dye or an antibody or aptamer
conjugated to a fluorescent tag. Pathogens may include bacteria,
fungi and/or viruses. The untethered ingestible device detects the
autofluorescence or reagent-induced fluorescence associated with
the pathogens and in real time delivers energy sufficient to
inactivate or ablate the pathogens. Optionally, the untethered
ingestible device detects the autofluorescence, wirelessly
transmits data to an external source, and at the discretion of the
physician or other medical practitioner, a trigger mechanism, for
example, is used to deliver energy sufficient to at least partially
inactivate or ablate the pathogens at the coordinates associated
with the autofluorescence.
[0194] Pathogens commonly associated with gastrointestinal
disorders include bacteria, such as certain strains of Escherichia
coli (e.g. Escherichia coli 0157:H7), various strains of
Salmonella, Vibrio cholera, Campylobacter, Listeria monocytogenes,
shigella, and Helicobacter pylori, viruses such as rotovirus and
Calicivirus, and parasites such as Giardia lamblia, Entamoeba
histolytica and Cryptosporidium.
[0195] A pathogen may be detected in the gastrointestinal tract
based on autofluorescence induced, for example, by electromagnetic
energy. In general, pathogens such as bacteria and fungi may be
detected by autofluorescence as described herein. For example,
Escherichia coli autofluorescence may be detected using excitation
wavelengths of 250-400 nm and examined at an emission wavelength of
495 nm and higher through, for example, a long pass optical filter
(Glazier, et al. (1994) J. Microbiol. Meth. 20:23-27; Hilton, et
al. (2000) Proc. SPIE 4087:1020-1026). Alternatively, Escherichia
coli autofluorescence maxima of 350 nm and 485 nm may be detected
following excitation at 290 nm (Cabreda, et al. (2007) J. Fluoresc.
17:171-180). Alternatively, Salmonella as well as Escherichia coli
autofluoresce when irradiated with electromagnetic energy at a
wavelength of 488 nm (Hilton (1998) SPIE 3491:1174-1178). The
Coccidia class of bacteria, which are transmitted through a
fecal-oral route via contaminated water and food and are associated
with watery diarrhea, may also be detected based on
autofluorescence (Bialek, et al. (2002) Am. J. Trop. Med. Hyg.
67:304-305). For example, Isospora belli and Cyclospora fluoresce a
bluish violet color under UV excitation (365 nm) and fluoresce a
bright green under violet excitation (405 nm).
[0196] A pathogen within the gastrointestinal tract may be
inactivated or killed by energy emitted from an untethered
ingestible device in response to detection of the pathogen by
autofluorescence using the same untethered ingestible device. In
general, pathogens such as bacteria and fungi may be inactivated or
killed by various wavelengths of electromagnetic energy as
described herein. For example, Escherichia coli may be partially or
completely inactivated, for example, by a 60 s exposure to a UV
electromagnetic energy source at wavelengths of 100-280 nm
(Anderson, et al. (2000) IEEE Transactions on Plasma Science
28:83-88). The intestinal parasites Cryptosporidium and Giardia may
also be at least partially inactivated or killed using UV
irradiation from, for example, a mercury arc lamp at a fluence of
40 mJ/cm.sup.2 (Li, et al. (2007) Appl. Environ. Microbiol.
73:2218-2223). Alternatively, Escherichia coli and Salmonella
enteritidis may be inactivated using pulsed broad-spectrum
electromagnetic energy with high UV content from, for example, a
Xenon lamp (Anderson, et al. (2000) IEEE Transactions on Plasma
Science 28:83-88). In this instance, targeted bacteria are
subjected to 100-1000 pulses of broad-spectrum light with each
pulse lasting, for example, 85 ns and having, for example, a power
output of 10 MW. Alternatively, a pathogen within the
gastrointestinal tract may be inactivated or killed by a particle
beam, or x-ray, or gamma ray electromagnetic energy, as described
herein.
[0197] Helicobacter pylori is a gram-negative bacterium which
selectively colonizes the stomach and duodenum and is associated
with chronic gastritis, gastric ulcer and increased risk for
gastric adenocarcinoma. H. pylori may be detected in the antrum of
the stomach by autofluorescence using an excitation wavelength, for
example, of 405 nm (Hammer-Wilson, et al. (2007) Scand. J.
Gastroenterol. 42:941-950). H. pylori naturally accumulates
coproporphyrin and protoporphyrin which sensitize the bacteria to
inactivation by visible light at wavelengths ranging from 375 to
425 nm (Hamblin, et al. (2005) Antimicrob. Agents Chemother.
49:2822-2827; U.S. Patent Application 2004/0039232 A1). As such, an
untethered ingestible device emitting electromagnetic energy as
described herein may be used to detect and at least partially
inactivate or kill H. pylori in the gastrointestinal tract.
[0198] The untethered ingestible device may transit through the
gastrointestinal tract by natural peristalsis after ingestion.
Transit times may vary depending, for example, on the time required
for gastric emptying and for transit through the small bowel. For
example, transit time of an untethered ingestible device out of the
stomach may range from 20-160 minutes depending upon, for example,
the age of the patient and whether polyethylene glycol (PEG 400) or
erythromycin are administered prior to and following ingestion of
the device (Fireman, et al. (2005) World J. Gastroenterol
11:5863-5866). Similarly, transit time through the small bowel may
range from 220-320 minutes depending, for example, upon the age of
the patient and co-administered agents (Fireman, et al. (2005)
World J. Gastroenterol 11:5863-5866).
[0199] The untethered ingestible device may be affixed to a
specific site within the gastrointestinal tract, for example, by
expanding to fill the lumen of the tract (U.S. Patent Application
2007/015621 A1). As such, the untethered ingestible device may be
cylindrical in shape with a central core enabling free flow of
fluids within the digestive tract.
[0200] Optionally, the untethered ingestible device may contain a
means of locomotion with internal or external control that allows
an operator to control movement of the device within the
gastrointestinal tract. The device may use a locomotion system
based on "inch-worm" motion using, for example, grippers and
extensors, rolling tracks, or rolling stents (Rentshcler, et al.
(2006) SAGES Meeting; Rentschler, et al. (2007) Surg. Endosc.
on-line ahead of publication). Alternatively, the device may use a
helical wheel configuration on its surface with, for example, two
independent motors that control the wheels, providing forward,
backward, and turning capacity (see, e.g., Rentshcler, et al.
(2006) SAGES Meeting; Rentschler, et al. (2007) Surg. Endosc.
on-line ahead of publication; U.S. Patent Application 2006/119304
A1). Alternatively, the device may use a locomotion system based on
wheels or expanding and contracting components (see, e.g., U.S.
Patent Application 2006/119304 A1).
Example 6
Detection and Ablation of Pathological Gastrointestinal Tissue with
an Untethered Ingestible Device
[0201] An untethered ingestible device may be used to detect and
ablate pathological gastrointestinal tissue in real time. The
device emits electromagnetic energy at wavelengths sufficient to
induce autofluorescence of pathological tissue within the
gastrointestinal tract. Alternatively, the device emits
electromagnetic energy at wavelengths sufficient to cause
fluorescence of reagents added to the gastrointestinal tract to
selectively detect pathological tissue, such as, for example, a
chemical dye or an antibody or aptamer conjugated to a fluorescent
tag. Pathological tissue may include, for example, cancer or
lesions associated with Crohns disease. The untethered ingestible
device detects the autofluorescence or reagent-induced fluorescence
associated with the pathological tissue and in real time delivers
energy sufficient to at least partially ablate the pathological
tissue. Optionally, the untethered ingestible device detects the
autofluorescence, wirelessly transmits data to an external source,
and at the discretion of the physician or other medical
practitioner, a trigger mechanism, for example, is used to deliver
energy sufficient to at least partially ablate the pathological
tissue at coordinates associated with the autofluorescence.
[0202] For example, changes in autofluorescence emission (350 to
700 nm) of premalignant or malignant lesions in the oral cavity
relative to normal tissue may be detected using excitation
wavelengths of 330, nm, 337 nm, 365 nm, and 410 nm (Gillenwater, et
al. (1998) Arch. Otolaryngol. Head Neck Surg. 124:1251-1258; Tsai,
et al. (2003) Lasers Surg. Med. 33:40-47). In this instance, the
fluorescence intensity of normal mucosa may be greater than that of
abnormal areas, while the ratio of red fluorescence (635 nm) to
blue fluorescence (455-490 nm) intensities may be greater in
abnormal areas. Alternatively, autofluorescence induced by
excitation wavelengths of 365, 385, 405, 420, 435, and 450 nm may
be combined with diffuse reflectance spectroscopy to detect
pre-malignant and malignant lesions in the oral mucosa (de Veld, et
al. (2005) Lasers Surg. Med. 36:356-364). Based on the relative
autofluorescence, the cancerous cells may be identified and
irradiated with electromagnetic energy sufficient to ablate the
cell or cells, as described herein.
[0203] Autofluorescence may be used to distinguish between normal
and neoplastic tissue in patients with Barrett's esophagus
(Borovika, et al. (2006) Endoscopy 38:867-872; Pfefer, et al.
(2003) Lasers Surg. Med. 32:10-16) For example, fluorescence
spectra excited at 337 nm and 400 nm may be used to distinguish
between normal and neoplastic tissue (Pfefer, et al. (2003) Lasers
Surg. Med. 32:10-16). Alternatively, fluorescence maxima may be
compared at various emission wavelengths, for example, 444, 469,
481, 486, 545, 609, and 636 nm following excitation at 337 nm and
400 nm. Autofluorescence may be observed with a long-pass filter
with a cut-off wavelength >470 nm to optimize fluorescence
detection and minimize excitation light (Borovika, et al. (2006)
Endoscopy 38:867-872). Alternatively, adenocarcinoma in patients
with Barrett's esophagus may be detected using electromagnetic
energy in combination with an agent that concentrates in cancerous
cells and that fluoresces upon laser excitation, such as, for
example, Photofrin.RTM. (von Holstein, et al. (1999) Gut
39:711-716).
[0204] Autofluorescence may be used to distinguish between normal,
hyperplastic and adenomatous colonic mucosa (DaCosta, et al. (2005)
J. Clin. Path. 58:766-774; Eker, et al. (1999) Gut 44:511-518).
Irradiation of colon mucosa with ultraviolet light or blue light
with a wavelength of 488 nm, for example, induces emission of green
and red regions of autofluorescence. In normal tissue, collagen and
elastin emit weak green fluorescence. In hyperplastic tissue or
polyps, increased collagen produces intense green fluorescence.
Dysplastic or malignant lesions may have enhanced red fluorescence
compared with either normal or hyperplastic polyps (DaCosta, et al.
(2005) J. Clin. Path. 58:766-774).
[0205] An untethered ingestible device emitting electromagnetic
energy at a wavelength or wavelengths sufficient to induce
autofluorescence such as ultraviolet or blue light, for example, is
used to irradiate the colon. Fluorescence emission is detected at
wavelengths of 505-550 nm and >585 nm, for example, to detect
the green and red autofluorescence, respectively. Alternatively,
shifts in the autofluorescence emission maxima following excitation
at 337 nm may be used to distinguish normal from adenomatous tissue
(Eker, et al. (1999) Gut 44:511-518).
[0206] Optionally, electromagnetic energy may be combined with
5-aminolevulinic acid (ALA) to differentiate between normal colon
tissue and adenomatous polyps (Eker, et al. (1999) Gut 44:511-518).
For example, ALA at a dose of 5 mg/kg body weight may be
administered orally to patients 2 to 3 hours prior to investigation
followed by irradiation of the colon tissue with excitation
wavelengths of 337 nm, 405 nm, and 436 nm. Normal versus abnormal
tissue may be distinguished based on relative shifts in the
emission maxima (Eker, et al. (1999) Gut 44:511-518).
[0207] Based on the relative autofluorescence, the cancerous cells
are identified and may be irradiated with energy sufficient to
ablate the cell or cells, as described herein. For example,
colorectal adenomas may be ablated using an Nd:YAG (1064 nm) with
maximal power output of 100 W (Norberto, et al. (2005) Surg.
Endosc. 19:1045-1048). Alternatively, X-ray energy administered at
a total dose of 20 Gy may be used to treat colon cancer (Kosmider,
et al. (2007) World J. Gastroenterol. 13:3788-3805).
[0208] Autofluorescence imaging may be used to detect the severity
of ulcerative colitis (Fujiya, et al. (2007) Dig. Endoscopy 19
(Suppl. 1):S145-S149). For example, differences in inflammatory
state may be distinguished by autofluorescence, with severely
inflamed mucosa associated with purple autofluorescence, atrophic
regenerative mucosa associated with faint purple autofluorescence
with green spots, and normal mucosa associated with green
autofluorescence.
Example 7
Detection and Ablation of Pathogens in a Lumen with an Untethered
Device
[0209] An untethered device may be used to detect and ablate
pathogens within a lumen in real time. The device emits
electromagnetic energy at wavelengths sufficient to induce
autofluorescence of pathogens within the lumen. Alternatively, the
device emits electromagnetic energy at wavelengths sufficient to
cause fluorescence of reagents added to the lumen to selectively
detect pathogens, such as, for example, a chemical dye or an
antibody or aptamer conjugated to a fluorescent tag. Pathogens may
include bacteria, fungi and/or viruses. A lumen may include that
associated with blood vessels, the urogenital tract, and the
respiratory tract, for example. The untethered luminal device
detects the autofluorescence or reagent-induced fluorescence
associated with the pathogens and in real time delivers energy
sufficient to inactivate or ablate the pathogens. Optionally, the
untethered luminal device detects the autofluorescence, wirelessly
transmits data to an external source, and at the discretion of the
physician or other medical practitioner, a trigger mechanism, for
example, is used to deliver energy sufficient to at least partially
ablate the pathogen at coordinates associated with the
autofluorescence.
[0210] An untethered device in the lumen of a blood vessel may be
used to detect and ablate pathogens associated with blood
infections or septicemia. Gram-negative enteric bacilli,
Staphylococcus aureus, and Streptococcus pneumoniae are the most
common pathogens in the United States associated with micronemia
and sepsis. As such, electromagnetic energy emitted from a luminal
device may be used to detect autofluorescence associated, for
example, with blood borne bacteria as described herein. The
pathogens are subsequently ablated using, for example, UV
electromagnetic energy as described herein.
[0211] An untethered device in the lumen of a blood vessel may be
used to detect and ablate parasites in the blood stream. For
example, autofluorescence associated with the food vacuole of the
malaria parasite Plasmodium spp. may be used to detect infected
erythrocytes with in the blood stream (Wissing, et al. (2002) J.
Biol. Chem. 277:37747-37755). As such, an untethered luminal device
may induce autofluorescence of parasites at a wavelength, for
example, of 488 nm (Wissing, et al. (2002) J. Biol. Chem.
277:37747-37755). Alternatively, erythrocytes infected with
Plasmodium spp. may be detected by pre-staining the cells with
acridine orange, which when excited at 490 nm emits green light at
530 nm (Wissing, et al. (2002) J. Biol. Chem. 277:37747-37755).
Other nucleic-acid binding dyes may be used for this purpose
including Hoechst 33258, thiazole orange, hydroethidine, and YOYO-1
(Li, et al. (2007) Cytometry 71A:297-307). As such, the dyes bind
to parasite DNA in the infected erythrocytes which are otherwise
free of DNA. Erythrocytes autofluoresce upon excitation at a
wavelength of 545 nm with an emission wavelength of 610 nm
associated with the heme porphyrin (Liu, et al. (2002) J. Cereb.
Blood Flow Metab. 22:1222-1230). As such, the untethered luminal
device may optionally first identify an erythrocyte based on
autofluorescence at one wavelength, followed by detection of a
parasite within the erythrocyte based on autofluorescence or dye
induced fluorescence at a second wavelength. The untethered luminal
device may detect fluorescence associated with infected
erythrocytes and in real time emit energy at wavelengths sufficient
to at least partially ablate the infected cells.
[0212] An untethered luminal device may be used to detect and
ablate pathogens associated with urinary tract infections (UTI),
for example, in the lumen of the bladder. For example, Escherichia
coli uropathogenic strains are the most common cause of urinary
tract infections (Finer, et al. (2004) Lancet Infect. Dis.
4:631-635). Escherichia coli may be detected in the bladder, for
example, using electromagnetic energy to induce autofluorescence as
described herein. An untethered luminal device may be inserted into
the bladder via a catheter. Once inserted, the untethered luminal
device may scan the internal surface of the bladder with
electromagnetic energy sufficient to induce autofluorescence of
pathogens. In response to autofluorescence, the untethered luminal
device may emit energy sufficient to at least partially inactivate
pathogens, as described herein.
[0213] Optionally, the untethered luminal device may be affixed to
a specific site within a lumen, for example, by expanding to fill
the lumen (see, e.g., U.S. Patent Application 2007/015621 A1). As
such, the untethered luminal device may be cylindrical in shape
with a central core enabling free flow of fluids within the lumen.
Alternatively, the untethered luminal device may be affixed to a
specific site within a lumen using, for example, a hook or
claw-like structure, an adhesive or glue-like material, or suction
(see, e.g., U.S. Patent Application 2007/015621 A1).
[0214] Optionally, the untethered luminal device may contain a
means of locomotion with internal or external control that allows
an operator to control movement of the device within the lumen by
means described herein. Alternatively, the untethered luminal
device may be controlled by external magnetic energy. For example,
an untethered luminal device in an artery, for example, may be
manipulated using a clinical magnetic resonance imaging system
(see, e.g., Mathieu, et al. Proceedings of the 2005 IEEE,
Engineering in Medicine and Biology 27.sup.th Annual Conference,
Shanghai, China, Sep. 1-4, 2005, 4850-4853; Martel, et al. (2007)
Applied Physics Letters 90:114105-1-3). As such, the untethered
luminal device may be constructed, at least in part, with
ferromagnetic material.
Example 9
Detection and Ablation of Pathological Tissue in a Lumen with an
Untethered Device
[0215] An untethered device may be used to detect and ablate
pathological tissue or cells within a lumen in real time. The
device emits electromagnetic energy at wavelengths sufficient to
induce autofluorescence of pathological tissue within the lumen.
Alternatively, the device emits electromagnetic energy at
wavelengths sufficient to cause fluorescence of reagents added to
the lumen to selectively detect pathological tissue, such as, for
example, a chemical dye or an antibody or aptamer conjugated to a
fluorescent tag. Pathological tissue may include cancer,
atherosclerosis, and inflammation, for example. A lumen may include
that associated with blood vessels, the urogenital tract, and the
respiratory tract, for example. The untethered luminal device
detects the autofluorescence or reagent-induced fluorescence
associated with the pathogens and in real time delivers energy
sufficient to inactivate or ablate the pathological tissue.
Optionally, the untethered luminal device detects the
autofluorescence, wirelessly transmits data to an external source,
and at the discretion of the physician or other medical
practitioner, a trigger mechanism, for example, is used to deliver
energy sufficient to at least partially ablate the pathological
tissue at coordinates associated with the autofluorescence.
[0216] An untethered device in the lumen of a blood vessel, for
example, may be used to detect and ablate tissue and cells
associated with, for example, an atherosclerotic plaque. For
example, autofluorescence associated with macrophages in a plaque
may be used to characterize an atherosclerotic lesion (Marcu, et
al. (2005) Atherosclerosis 181:295-303). The accumulation of
macrophages in the fibrous cap of an atherosclerotic plaque are
indicative of inflammation as well as instability of the plaque.
The lumen of a blood vessel may be irradiated, for example, with 1
ns pulses of electromagnetic energy at a wavelength of 337 nm. The
resulting autofluorescence may be detected at specific maxima
wavelengths, for example, 395 nm and 450 nm, or over a range of
wavelengths, for example, from 300-600 nm (Marcu, et al. (2005)
Atherosclerosis 181:295-303). Differences in the autofluorescence
spectra may be used to differentiate between normal, collagen thick
and macrophage thick plaques (Marcu, et al. (2005) Atherosclerosis
181:295-303). Alternatively, the lumen of a blood vessel may be
irradiated with electromagnetic energy ranging in wavelength from
350 to 390 nm and the resulting autofluorescence detected at
critical wavelengths, for example, of 570, 600, 480, or 500 nm may
be sufficient to differentiate between structurally viable tissue
and an atherosclerotic plaque (U.S. Pat. No. 5,046,501).
[0217] The untethered device may subsequently in real time emit
energy sufficient to at least partially ablate the atherosclerotic
plaque based on the differential autofluorescence. An eximer laser
operating in the ultraviolet range may be used to ablate an
atherosclerotic plaque (Morguet, et al. (1994) Lasers Surg. Med.
14:238-248). Alternatively, other laser systems may be used to
ablate an atherosclerotic plaque, including, for example, a CO2
laser, Nd:YAG laser or an argon laser (Morguet, et al. (1994)
Lasers Surg. Med. 14:238-248).
[0218] An untethered device in the lumen of a blood vessel, for
example, may be used to detect and ablate cells associated with,
for example, a hematological form of cancer. For example, leukemia
is characterized by an increase in immature lymphoblasts in
circulation. These cells may have a distinct autofluorescence
relative to normal lymphocytes. As such, fluorescence associated
with the lymphoblasts may be detected and the cells subsequently
ablated using the methods described herein.
[0219] An untethered device in the lumen of a blood vessel may be
used to detect and ablate cells that have migrated from a solid
tumor and are on route to metastasis elsewhere in the body. These
cells may be identified using the untethered device to generate and
detect autofluorescence. Alternatively, these cells may be
identified using the untethered device to induce and detect
fluorescence associated with a reagent that specifically binds to a
cancer cell, such as a fluorescent antibody or aptamer. For
example, circulating tumor cells associated with breast cancer may
be detected using a fluorescently tagged antibody or aptamer to a
tumor specific cell-surface antigen such as, for example, the
Her2/Neu epidermal growth factor receptor (Gilbey, et al. (2004) J.
Clin. Pathol. 57:903-911). Patients with increased breast
epithelial cells in circulation have a higher rate of metastasis
and poorer outcome. As such, fluorescence associated with the
breast cancer cell may be detected and the cell subsequently
ablated by the untethered luminal device using the methods
described herein.
Example 10
Detection and Ablation of Pathogens in a Lumen with a Tethered
Device
[0220] A tethered device may be used to detect and ablate pathogens
within a lumen in real time. The device emits electromagnetic
energy at wavelengths sufficient to induce autofluorescence of
pathogens within the lumen. Alternatively, the device emits
electromagnetic energy at wavelengths sufficient to cause
fluorescence of reagents added to the lumen to selectively detect
pathogens, such as, for example, a chemical dye or an antibody or
aptamer conjugated to a fluorescent tag. Pathogens may include
bacteria, fungi and/or viruses. A lumen may include that associated
with blood vessels, gastrointestinal tract, the urogenital tract,
or the respiratory tract, for example. The tethered luminal device
detects the autofluorescence or reagent-induced fluorescence
associated with the pathogens and in real time delivers energy
sufficient to inactivate or ablate the pathogens.
[0221] A tethered device in the lumen of a blood vessel, for
example, may be used to detect and ablate pathogens in the blood
such as those associated with septicemia and malaria using
electromagnetic energy, as described herein.
[0222] A tethered device in the lumen of the lung, for example, may
be used to detect and ablate pathogens associated with bronchial
infections, such as bronchitis, pneumonia, and tuberculosis.
Streptococcus pneumoniae is the most common cause of
community-acquired pneumonias whereas Pseudomonas aeruginosa,
Escherichia coli, Enterobacter, Proteus, and Klebsiella are
commonly associated with nosocomial-acquired pneumonia. Although
the incidence of tuberculosis is low in industrialized countries,
M. tuberculosis infections still continue to be a significant
public health problem in the United States, particularly among
immigrants from developing countries, intravenous drug abusers,
patients infected with human immunodeficiency virus (HIV), and the
institutionalized elderly. Autofluorescence induced by
electromagnetic energy may be used to detect various bacterial
pathogens, as described herein. A tethered device may be inserted
into the lung comparable, for example, to a bronchoscope, and used
to detect pathogens. In response to autofluorescence, the same
tethered device may emit in real time energy sufficient to at least
partially inactivate pathogens, as described herein.
Example 11
Detection and Ablation of Pathological Tissue in a Lumen with
Tethered Device
[0223] A tethered device may be used to detect and ablate
pathological tissue or cells within a lumen in real time. The
device emits electromagnetic energy at wavelengths sufficient to
induce autofluorescence of pathological tissue within the lumen.
Alternatively, the device emits electromagnetic energy at
wavelengths sufficient to cause fluorescence of reagents added to
the lumen to selectively detect pathological tissue, such as, for
example, a chemical dye or an antibody or aptamer conjugated to a
fluorescent tag. Pathological tissue may include cancer,
atherosclerosis, and inflammation, for example. A lumen may include
those associated with blood vessels, the urogenital tract, the
gastrointestinal tract, or the respiratory tract, for example. The
tethered luminal device detects the autofluorescence or
reagent-induced fluorescence associated with the pathological
tissue and in real time automatically delivers energy sufficient to
at least partially ablate the pathological tissue.
[0224] Autofluorescence induced by an optical energy source may be
used to detect pathological tissue as described herein.
Alternatively, fluorescence associated with a selective marker may
be induced by an optical energy source to detect pathological
tissue as described herein. A tethered device that emits optical
energy to induce autofluorescence of pathological tissue may be
configured, for example, like an endoscope (see, e.g., U.S. Pat.
No. 5,507,287; U.S. Pat. No. 5,590,660; U.S. Pat. No. 5,647,368;
U.S. Pat. No. 5,769,792; U.S. Pat. No. 6,061,591; U.S. Pat. No.
6,123,719; U.S. Pat. No. 6,462,770B1). As such, a flexible optical
tube sufficiently small enough to be inserted into a lumen may be
attached to an optical energy source that emits wavelengths
sufficient to induce autofluorescence such as for example, a
nitrogen laser. The same flexible tube may transmit the emitted
autofluorescence back to a CCD camera and control circuitry.
Immediately upon receiving the emitted autofluorescence indicative
of pathological tissue, a second emission of energy, from for
example an Nd:YAG laser, is released to at least partially ablate
the pathological tissue. Alternatively, the head of the flexible
tube may contain a photodiode array sensor that directly detects
the autofluorescence and triggers a second emission of energy
sufficient to at least partially ablate the pathological tissue.
Alternatively, the head of the flexible tube may contain shielded
gamma emitting isotopes that exposure the tissue to radiation in
real time in response to the detected autofluorescence.
[0225] A tethered device in the lumen of a blood vessel, for
example, may be used to detect and ablate pathological tissue, for
example, atherosclerotic plaques or circulating cancer cells as
described herein.
[0226] Autofluorescence in combination with reflected light may be
used to differentiate between normal, inflamed and pre-invasive
lesions in the lung (Chiyo, et al. (2005) Lung Cancer 48:307-313;
Gabrecht, et al. (2007) SPIE-OSA Vol. 6628, 66208C-1-8; US U.S.
Pat. No. 5,507,287). For example, bronchial tissue may be
irradiated with excitation wavelengths of 395-445 nm and
autofluorescence detected at wavelengths of 490-690 nm.
Simultaneously or subsequently, reflected light at 550 nm (green)
and at 610 nm (red) may be collected and combined with the
autofluorescence data to form a composite image. As such, the
ratios of green/red and green/autofluorescence may be greater in
squamous dysplasia relative to inflamed lung tissue associated with
bronchitis, allowing for differentiation between these two disease
states (Chiyo, et al. (2005) Lung Cancer 48:307-313). Based on the
relative autofluorescence detected, the tethered device emits
energy sufficient to at least partially ablate the cancerous
tissue. For example, electromagnetic energy sufficient to ablate
cancerous cells in the lung may be generated by a Neodynium YAG
laser (1064 nm) with power output up to 100 W and tissue
penetration of 1-5 mm (Hansen, et al. (2006) Minim. Invasive Ther.
Allied Technol. 15:4-8).
Example 12
An Apparatus for Detection and Ablation of Pathogens and
Pathological Tissue
[0227] FIG. 26, FIG. 27, and FIG. 28 show illustrative
configurations of handheld versions of an apparatus 100 of FIG. 1.
for the detection and ablation of pathogens and pathological
tissue.
[0228] FIG. 26 shows an illustrative configuration of a handheld
device 2000 which is completely self-contained and easily held in
the hand of the user 2001. The user 2001 may be, for example, a
surgeon or other medical practitioner and/or a veterinarian, using
the handheld device 2000, for example, in a surgical theater, a
hospital emergency room, a doctor, dentist, veterinary, or nurse
practitioner's office. Alternatively, the user 2001 may be an
emergency responder, using the hand held device 2000, for example,
out in the field at the site of an accident or on the battlefield.
The user 2001 may hold the handheld device 2000 in proximity to a
lesion or lesions 2002 on a patient 2003. The lesion 2002 may be a
surgical incision or a wound. A wound, for example, may be an
abrasion, a burn, a puncture, or a deep gouge. Alternatively, the
lesion 2002 may be on the surface of the skin or the surface of the
oral cavity. The user 2001 turns on the handheld device 2000 using
an on/off switch 2004. Optionally, the user 2001 may use a button
2005 on the handheld device 2000 to activate or enable a beam of
energy 2006 (optionally the same as 110). The user 2001 activates a
beam of energy 2006 in proximity to the lesion 2002 to detect and
ablate pathogens and pathological tissue.
[0229] FIG. 27 shows an illustrative configuration of a handheld
device 2007 which is held in the hand of the user 2001 and is
optionally wirelessly connected to optional external control
circuitry 2008. Optionally, the handheld device 2007 is connected
via a wire 2009 to external control circuitry 2008 or an external
power source 2010, or both. The user 2001 activates a beam of
energy 2006 in proximity to the lesion 2002 to detect and ablate
pathogens and pathological tissue.
[0230] FIG. 28 shows an illustrative configuration of a handheld
device 2011 which is held in the hand of the user 2001, and is used
in conjunction with targeting aids 2014 surrounding the lesion 2002
on the surface of the patient 2003. The targeting aids 2014 are
used, for example, to register the position of autofluorescence
associated with pathogens or pathological tissue within the lesion
2002 with respect to the surface of the patient 2003. As such, the
user 2001 may screen the entire lesion 2002, noting the position of
possible pathogens or pathological tissue. The user 2001 may
subsequently return to specific regions of concern and at the
discretion of the user 2001, manually initiate ablation using, for
example, a trigger 2012. The handheld device 2011 may include a
monitor 2013 that allows the user 2001 to observe the
autofluorescence emitted from the lesion 2002 in real time and/or
to observe a targeting beam of optionally visual light indicating
the location of emitted energy for excitation and/or ablation.
[0231] Alternatively, the handheld device may be connected to an
external display device and control circuitry 2008 as described in
FIG. 27. The user 2001 places at least three targeting aids around
the lesion 2002 on the patient 2003. The user 2001 scans the
surface of the lesion 2002 with the handheld device 2011 and data
is collected regarding the position of autofluorescence associated
with a pathogen or pathological tissue. The user 2001 may analyze
the accumulated data and at the discretion of the user 2001, return
to specific regions of the lesion 2002 and use the trigger 2012 to
initiate or enable irradiation with a beam of energy 2006 to ablate
pathogens or pathological tissue. Alternatively, the targeting aids
2014 may be placed on fixed surfaces, for example, of the
examination room. As such, the extremity with the lesion 2002 is
immobilized to an examining surface, for example, to aide in
location registration.
[0232] FIG. 29 shows an illustrative configuration of a stationary
version of the apparatus 100 for the real time detection and
ablation of pathogens and pathological tissue. The stationary
device 2015 may be a component of a room 2016 that is, for example,
part of a surgical theater, an imaging and treatment facility, or a
doctor's or dentist's or veterinarian's office. The stationary
device 2015 may be used in conjunction with targeting aids 2014
placed at various locations around the room 2016. In the example
shown in FIG. 29, the targeting aids 2014 are affixed to the walls
2017 of the room 2016. Alternatively, the targeting aids 2014 may
be affixed to the ceiling, to the floor or to objects within the
room, or a combination thereof.
[0233] The user 2001 may control the stationary device 2015 using
control circuitry 2008 optionally in an auxiliary room 2018
optionally visually connected to the main room 2016 by a window or
other viewing means, for example. The room 2016 may also contain a
table 2019 upon which there is optionally a sliding platform 2020
for moving the patient 2003 into position relative to the
stationary device 2015. The sliding platform 2020 may also have
strategically placed targeting aids 2014. Alternatively, targeting
aids 2014 may be placed on the patient 2003 in proximity to the
lesion 2002 as described herein. In an alternative configuration,
the patient 2003 may remain stationary on a table 2019 while some
component of the stationary device 2015 is moved into the
appropriate position relative to the lesion 2002.
[0234] The user 2001 may scan a lesion 2002 with the stationary
device 2015 using a beam of energy 2006 to detect autofluorescence
associated with pathogens or pathological tissue. The beam of
energy 2006 exciting the autofluorescence associated with the
pathogen or pathological tissue may be emitted, for example, from a
mercury arc lamp, a Xenon lamp, a UV eximer, a halogen lamp, a
laser or light emitting diode at wavelengths ranging, for example,
from 200 nm to 1000 nm. The stationary device 2015 may
automatically ablate the pathogen or pathological tissue based on
the emitted autofluorescence. Alternatively, data may be collected
regarding the position of autofluorescence associated with a
pathogen or pathological tissue. The user 2001 may analyze the
accumulated data and at the discretion of the user 2001, return to
a specific region of the lesion 2002 based on orientation from the
targeting aids 2014 and instruct the stationary device 2015 to emit
a second beam of energy 2006 to ablate pathogens or pathological
tissue. The second beam of energy 2006 may or may not be of the
same wavelength and intensity as the first beam of energy 2006 used
to excite fluorescence. The beam of energy 2006 inducing ablation
of pathogens or pathological tissue may be an optical energy
source, such as those described above, an X-ray energy source, a
particle beam energy source, or a combination thereof.
[0235] FIG. 30, FIG. 31, and FIG. 32 show schematic representations
of illustrative configurations of handheld versions of an apparatus
100 for the detection and ablation of pathogens and pathological
tissue.
[0236] FIG. 30 shows a schematic representation of an illustrative
configuration of a completely self-contained handheld device 2021
for the detection and ablation of pathogens and pathological
tissue. The handheld device 2021 contains a power source 2022 which
powers the control circuitry 2023, the optical energy source 2024,
and other components of the device 2021. The optical energy source
2024 may be, for example, a mercury arc lamp, a Xenon lamp, a UV
eximer, a halogen lamp, a nitrogen laser or a laser diode. The
electromagnetic energy 2029 emitted from the optical energy source
2024 may pass through a filter 2025 that allows for emission of
specific wavelengths appropriate for inducing autofluorescence of
pathogens or pathological tissue as described herein. The
electromagnetic energy 2029 may pass through a lens 2026 to focus
the energy and optionally through a chromatic beam splitter 2027.
The electromagnetic energy 2029 hits the lesion 2002 resulting in
emission of autofluorescence 2030. The autofluorescence 2030 is
detected by a sensor 2028 and as a result a second wave of
electromagnetic energy 2029 is emitted in real time from the
optical energy source 2024 at a wavelength and intensity sufficient
to ablate the detected pathogen or pathological tissue as described
herein.
[0237] FIG. 31 shows a schematic representation of an illustrative
configuration of a handheld device 2031 in which separate energy
sources are optionally used for detection and ablation of pathogens
or pathological tissue. The handheld device 2031 may be powered by
an internal power supply 2022. Optionally, the handheld device may
be connected to an external power supply. The handheld device 2031
may be controlled by internal control circuitry 2023. Optionally,
the handheld device 2031 may be connected either with or without
wires to external control circuitry. The handheld device 2031
contains at least one optical energy source 2032. The handheld
device 2031 may also contain a least one additional energy source
2033 for the ablation of pathogens or pathological tissue. The
energy source 2033 may be an optical energy source, an X-ray
source, or a particle beam source, or a combination thereof.
[0238] Electromagnetic energy 2029 emitted from the optical energy
source 2032 may pass through a filter 2025 that allows for emission
of specific wavelengths appropriate for inducing autofluorescence
of pathogens or pathological tissue as described herein. The
electromagnetic energy 2029 may pass through a lens 2026, a series
of beam splitters 2027, and through a final lens 2026 prior to
hitting the lesion 2002. The autofluorescence 2030 emitted by
pathogens or pathological tissue in the lesion 2002 is detected by
the sensor 2028. As a result, a second beam of electromagnetic
energy 2029 may be emitted from the first optical energy source
2032. Alternatively, a second beam of energy 2034 may be emitted
from the second energy source 2033 which is a level of energy
sufficient to ablate a pathogen or pathological tissue as described
herein. The ablation energy may pass through portions of the same
beam path, or may use a fully or partially dedicated beam path.
[0239] FIG. 32 shows a schematic representation of an illustrative
configuration of a handheld device 2035 in which multiple energy
sources are optionally used for position, detection and ablation of
pathogens or pathological tissue. As shown in FIG. 32A, the
handheld device 2035 may include a monitor 2036 for observing the
autofluorescence associated with a pathogen or a pathological
tissue. Optionally, the handheld device 2035 may be connected with
or without wires to an external display device. The handheld device
2035 may include a control panel 2037 allowing for entry of
commands by the user. Optionally, the handheld device 2035 may be
connected with or without wires to an external control panel
associated, for example, with a computer. The handheld device may
be turned on and off via a switch 2004.
[0240] As shown in FIG. 32B, the handheld device 2035 may be
powered by an internal power supply 2022. Optionally, the handheld
device may be connected to an external power supply. The handheld
device 2035 may be controlled by internal control circuitry 2023.
Optionally, the handheld device 2035 may be connected either with
or without wires to external control circuitry. The handheld device
2035 contains at least one optical energy source 2032. The handheld
device 2035 may also contain at least two additional energy sources
2033 for the ablation of pathogens or pathological tissue. The
energy source 2033 may be an optical energy source, an X-ray
source, or a particle beam source, or a combination thereof. The
handheld device 2035 may also contain at least one targeting energy
source 2038 for positioning the autofluorescence associated with a
pathogen or pathological tissue relative to one or more targeting
sensors, as described herein.
[0241] Energy emitted from the optical energy source 2032 may pass
through a filter/focus unit 2039 that allows for emission of
specific wavelengths appropriate for inducing autofluorescence of
pathogens or pathological tissue as described herein. The
autofluorescence emitted by pathogens or pathological tissue in a
lesion is detected by the sensor 2028. The position of the
autofluorescence in the lesion may be determined with the aide of
the targeting energy source 2038 and targeting sensors positioned,
for example, on the surface of the patient in proximity to the
lesion or on various surfaces in a room or a combination thereof as
described herein. After the autofluorescence is detected, a second
beam of electromagnetic energy may be emitted from the first
optical energy source 2032. Alternatively, a second beam of energy
may be emitted from the second or third energy source 2033 at a
level of energy sufficient to ablate a pathogen or pathological
tissue as described herein.
[0242] As shown in FIG. 32C, energy emitted from or detected by the
device 2035 passes through one or more openings 2040 at the bottom
of the device 2035.
[0243] FIG. 33 and FIG. 34 show illustrative configurations of
untethered versions of a device 200, 300 and/or 400 for the
detection and ablation of pathogens and pathological tissue in the
lumen, for example, of a blood vessel.
[0244] FIG. 33 shows an illustrative configuration of an untethered
device 2041 for the detection and ablation of pathogens and
pathological tissue in the lumen 2042 of a blood vessel, for
example. Alternatively, the untethered device 2041 may be used in
other lumens including those associated with the gastrointestinal
tract, the respiratory tract, and the urogenital tract, for
example. In this configuration, the untethered device 2041 may be a
hollow cylinder that when placed in a lumen 2042 allows for the
flow of fluid and cells 2043 through the central core 2045 of the
cylinder. The hollow cylinder contains a detection and ablation
unit 2047, which optionally contains a power source, control
circuitry, one or more energy sources, and a sensor. Control of the
device may be completely self-contained or controlled wirelessly by
an external user.
[0245] As normal cells 2043 and abnormal cells 2044 pass through
the central core 2045 of the untethered device 2041, the detection
and ablation unit 2047 detects autofluorescence associated with the
abnormal cells 2044 and in real time ablates the abnormal cells
2044. Abnormal cells 2044 may be, for example, pathogens,
pathological cells or cancerous cells as described herein. The
untethered device 2041 may be reversibly fixed in a specific region
of the lumen by virtue of inflatable pouches 2046 or other
means.
[0246] FIG. 34 shows an illustrative configuration of an untethered
device 2048 for the detection and ablation of pathogens and
pathological tissue in the lumen 2042, for example, of a blood
vessel. Alternatively, the untethered device 2048 may be used in
other lumens including those associated with the gastrointestinal
tract, the respiratory tract, and the urogenital tract, for
example. In this configuration, the untethered device 2048 may be
fixed to the surface of a lumen by virtue of a hook 2049 which at
the appropriate time and location latches on to the surface of the
lumen. Control of the untethered device 2048 may be completely
self-contained or controlled wirelessly by an external user. The
untethered device 2048 may sit on the surface of a lumen and
monitor the flow of fluid and normal cells 2043 and abnormal cells
2044. The untethered device 2048 emits a beam of energy 2006 which
detects abnormal cells 2044 based on autofluorescence and in real
time ablates the abnormal cells.
[0247] FIG. 35, FIG. 36, and FIG. 37 show illustrative
configurations of untethered versions of an apparatus 100 with
controlled locomotion for the detection and ablation of pathogens
and pathological tissue in a lumen associated with, for example,
the circulatory system, the gastrointestinal tract, the respiratory
tract, or the urogenital tract.
[0248] FIG. 35 shows an illustrative configuration of an untethered
device 2050 with controlled locomotion for the detection and
ablation of pathogens and pathological tissue in a lumen 2042. In
this configuration, the untethered device 2050 is a hollow cylinder
and has two or more controllable wheels 2051 that allow the device
to move along the surface of a lumen. Control of the movement of
the untethered device 2050 may be completely self-contained or
controlled wirelessly by an external user. The hollow cylinder
contains a detection and ablation unit 2047, which optionally
contains a power source, control circuitry, one or more energy
sources, and a sensor. As the untethered device moves along the
surface of a lumen, a beam of energy 2006 is emitted towards the
surface, for example, scanning for autofluorescence associated with
a pathogen or pathological tissue. Once autofluorescence is
detected, the untethered device 2050 emits a beam of energy 2006
from the detection and ablation unit 2047 sufficient to ablate the
pathogen or pathological tissue.
[0249] FIG. 36 shows an illustrative configuration of an untethered
device 2052 with controlled locomotion for the detection and
ablation of pathogens and pathological tissue in a lumen 2042. In
the configuration shown, the untethered device 2052 is a sphere.
Optionally, the untethered device 2052 may be any configuration
that is compatible with housing the components necessary for
detection and ablation of pathogens or pathological tissue in a
lumen 2042. The untethered device 2052 has two propellers 2053
mounted on the top and on the side of the sphere to allow the
controlled movement of the device in all directions. Optionally,
more or less propellers 2053 may be mounted on the device.
Optionally, the one or more propellers 2053 may be mounted in
different locations on the device. Control of the movement of the
untethered device 2052 may be completely self-contained or
controlled wirelessly by an external user. As shown, the untethered
device 2052 contains an energy source 2054, control circuitry,
2055, a sensor 2056, and a power source 2057. The energy source
2054 may be an optical energy source, an x-ray energy source, a
particle beam energy source, or a combination thereof. The
untethered device 2052 moves through a lumen 2042 scanning the
surface of the lumen or cells flowing in the lumen with
electromagnetic energy 2029 (optionally the same as 111) sufficient
to induce autofluorescence associated with a pathogen or
pathological cell or tissue. Once autofluorescence is detected by
the sensor 2056, the untethered device 2052 emits energy sufficient
to ablate the pathogen or pathological tissue.
[0250] FIG. 37 shows an illustrative configuration of an untethered
device 2058 with controlled locomotion for the detection and
ablation of pathogens and pathological tissue in a lumen 2042. In
this configuration, the two halves of the untethered device 2058
have grooves 2059 cut in opposite directions. The two halves of the
untethered device 2058 rotate independently in opposite directions.
Control of the movement of the untethered device 2058 may be
completely self-contained or controlled wirelessly by an external
user. Each half of the untethered device may have the independent
capability of emitting and detecting a beam of energy 2006
sufficient to detect and ablate pathogens or pathological
tissue.
[0251] FIG. 38 and FIG. 39 show illustrative configurations of
untethered versions of an apparatus 100 with random movement for
the detection and ablation of pathogens and pathological tissue in
a lumen associated with, for example, the circulatory system, the
gastrointestinal tract, the respiratory tract, or the urogenital
tract.
[0252] FIG. 38 shows an illustrative configuration of an untethered
device 2060 with random movement for the detection and ablation of
pathogens and pathological tissue in a lumen. In this
configuration, the untethered device 2060 is a sphere. Optionally,
the untethered device 2060 may be any configuration that is
compatible with housing the components necessary for detection and
ablation of pathogens or pathological tissue in a lumen 2042. The
untethered device 2060 has one or more controllable arms 2061
attached to the surface. A paddle 2062 is attached to the end of
each controllable arm 2061. The one or more arms 2061 may move in
varied directions relative to the surface of the untethered device
and as such, randomly turn the untethered device 2060. Control of
the movement of the arms 2061 of the untethered device 2060 may be
completely self-contained or controlled wirelessly by an external
user. The untethered device 2060 randomly rotates based on the
motion of the arms 2061 and associated paddles 2062, scanning the
surface of a lumen 2042 with a beam of energy 2006 sufficient to
induce autofluorescence. Once autofluorescence associated with a
pathogen or pathological tissue is detected, the untethered device
2060 emits energy sufficient to ablate the pathogen or pathological
tissue.
[0253] FIG. 39 shows an illustrative configuration of an untethered
device 2063 with random movement for the detection and ablation of
pathogens and pathological tissue in a lumen. In this
configuration, the untethered device 2063 is a sphere with two or
more tracks 2064 within the interior of the sphere. Each track 2064
has at least one associated weighted bead 2065 that is propelled
along the track 2064. Differential movement of the weighted beads
will cause random rotation of the untethered device 2063. The
untethered device 2063 randomly rotates based on the motion of the
two or more weighted beads, scanning the surface of a lumen 2042
with a beam of energy 2006, optionally electromagnetic energy 2029
from a detection and ablation unit 2047 sufficient to induce
autofluorescence. Once autofluorescence associated with a pathogen
or pathological tissue is detected, the untethered device 2063
emits a beam of energy 2006 from the detection and ablation unit
2047 sufficient to ablate the pathogen or pathological tissue.
[0254] FIG. 40 shows an illustrative configuration of an untethered
ingestible device 2066 for the detection and ablation of pathogens
and pathological tissue in the lumen of the gastrointestinal tract
2067. In the configuration shown, the untethered ingestible device
is a sphere with multiple openings 2068 covering the surface of the
sphere. The multiple openings 2068 may emit electromagnetic energy
2029 sufficient to induce autofluorescence of a pathogen or
pathological tissue and/or pathogen cell death. The emitted
autofluorescence 2070 induced by the electromagnetic energy 2029 is
detected through one or more of the multiple openings 2068. Once
autofluorescence associated with a pathogen or pathological tissue
is detected, the untethered ingestible device 2066 emits energy
sufficient to ablate the pathogen or pathological tissue.
[0255] In one aspect, the disclosure is drawn to systems
implementations including methods, computer programs, and systems
for controlling optionally the detection and ablation and/or
movement of targets optionally at least partially based on a
fluorescent response. One or more of these systems implementations
may be used as part of one or more methods for optionally detecting
and ablating one or more targets optionally at least partially
based on a fluorescent response, and/or implemented on one or more
apparatus 100 and/or 500 and/or devices 200, 300, and/or 400
optionally configured to detect and/or to ablate one or more target
cells. One or more of the operations, computer programs, and/or
systems implementations described in association with one or more
embodiments are envisioned and intended to also make part of other
embodiments unless context indicates otherwise.
[0256] The operational flows may also be executed in a variety of
other contexts and environments, and or in modified versions of
those described herein. In addition, although some of the
operational flows are presented in sequence, the various operations
may be performed in various repetitions, concurrently, and/or in
other orders than those that are illustrated. Although several
operational flow sequences are described separately herein, these
operational flows may be performed in sequence, in various
repetitions, concurrently, and in a variety of orders not
specifically illustrated herein. In addition, one or more of the
steps described for one or more operational flow sequence may be
added to another flow sequence and/or used to replace one or more
steps in the flow sequence, with or without deletion of one or more
steps of the flow sequence.
[0257] Operations may be performed with respect to a digital
representation (e.g. digital data) of, for example, one or more
characteristics of a fluorescent response, one or more
characteristics of excitation energy 116, one or more
characteristics of ablation energy 117, one or more movement
parameters, and/or one or more targeting parameters. The logic may
accept a digital or analog (for conversion into digital)
representation of an input and/or provide a digitally-encoded
representation of a graphical illustration, where the input may be
implemented and/or accessed locally or remotely. The logic may
provide a digital representation of an output, wherein the output
may be sent and/or accessed locally or remotely.
[0258] Operations may be performed related to either a local or a
remote storage of the digital data, or to another type of
transmission of the digital data. In addition to inputting,
accessing querying, recalling, calculating, determining or
otherwise obtaining the digital data, operations may be performed
related to storing, assigning, associating, displaying or otherwise
archiving the digital data to a memory, including for example,
sending, outputting, and/or receiving a transmission of the digital
data from (and/or to) a remote memory and/or unit, device, or
apparatus. Accordingly, any such operations may involve elements
including at least an operator (e.g. human or computer) directing
the operation, a transmitting computer, and/or receiving computer,
and should be understood to occur in the United States as long as
at least one of these elements resides in the United States.
[0259] FIG. 8 and/or FIG. 9 depict embodiments of an operational
flow 600 representing illustrative embodiments of operations
related to providing a first output to a first energy source in
real time, the first output providing data associated with at least
partial ablation of a target at least partially based on the first
possible dataset. In FIG. 8 and/or FIG. 9, discussion and
explanation may be provided with respect to one or more apparatus
100 and/or 500 and/or device 200, 300 and/or 400 and methods
described herein, and/or with respect to other examples and
contexts.
[0260] In some embodiments, one or more methods include receiving a
first input associated with a first possible dataset, the first
possible dataset including data representative of a target
fluorescent response; and providing a first output to a first
energy source in real time, the first output providing data
associated with at least partial ablation of a target at least
partially based on the first possible dataset. In illustrative
embodiments, operational flow 600 may be employed in the process of
target ablation to receive information associated with a target
fluorescent response optionally from one or more apparatus 100
and/or 500 and/or devices 200, 300, and/or 400, optionally
including, but not limited to, information relating to the
wavelength, intensity, strength, directionality, and/or spatial
extent of the fluorescent response. In illustrative embodiments,
operational flow 600 may be employed in the process of target
ablation to analyze information associated with a target
fluorescent response, optionally from one or more apparatus 100
and/or 500 and/or devices 200, 300, and/or 400, to determine one or
more characteristics of one or more energy source 110 and/or
ablation energy 117 associated with at least partially ablating one
or more target.
[0261] After a start operation, the operational flow 600 moves to a
receiving operation 160, receiving a first input associated with a
first possible dataset, the first possible dataset including data
representative of one or more target fluorescent response. For
example, a first input may include, but is not limited to, data
representative of one or more wavelengths of excitation energy,
direction, pulse time, timing, as well as detection wavelengths and
timing. For example, a first input may include, but is not limited
to, a condition, an illness, a cell and/or tissue type under
investigation, and/or other disease and/or preventive medicine
information
[0262] An optional accessing operation 260 accesses the first
possible dataset in response to the first input. For example, data
representative of one or more fluorescent responses, one or more
autofluorescent responses, and/or one or more target fluorescent
responses may be accessed. For example, data representative of
background fluorescence, fluorescent tags and/or markers, and/or
limits of detection may be accessed.
[0263] An optional generating operation 360 generates the first
possible dataset in response to the first input. For example, data
representative of one or more target fluorescent response may be
generated optionally by eliminating and/or controlling for
endogenous non-target fluorescence and/or non-specific
fluorescence. For example, data representative of direction and/or
location of a target, the presence or absence of a target, and/or
the risk to non-target cells and tissues of ablation may be
generated.
[0264] An optional determining operation 460 determines a graphical
illustration of the first possible dataset. For example, data
representative of one or more fluorescent responses, one or more
autofluorescent responses, and/or one or more target fluorescent
response may be graphically represented. For example, data
representative of direction and/or location of a target optionally
in relation to other non-target areas and/or the likelihood of
collateral damage may be graphically represented.
[0265] An optional sending operation 560 sends the first output
associated with the first possible dataset. For example, data
representative of one or more fluorescent responses, one or more
autofluorescent responses, and/or one or more target fluorescent
response may be sent as part of the first output. For example, data
representative of direction and/or location of a target may be sent
optionally to an external source and/or to an ablation device.
[0266] An optional determining operation 660 determines data
representative of one or more characteristics of excitation energy
116 for inducing the target fluorescent response. For example, data
representative of one or more characteristics of excitation energy
116, optionally including, but not limited to, wavelength,
strength, mode, directionality, and/or spatial limitations may be
determined.
[0267] An optional determining operation 760 determines data
representative of one or more characteristics of ablation energy
117 for at least partially ablating a target. For example, data
representative of one or more characteristics of ablation energy
117, optionally including, but not limited to, wavelength,
strength, mode, directionality, and/or spatial limitations may be
determined.
[0268] An optional operation 860 includes an optional receiving
operation 862 and an optional determining operation 864. The
optional receiving operation 862 receives a second input associated
with a second possible dataset, the second possible dataset
including data representative of a second target fluorescent
response following the at least partial ablation of the target. The
optional determining operation 864 determines data representative
of one or more characteristics of ablation energy 117 for further
ablating a target at least partially based on the second possible
dataset. For example, data representative of a second target
fluorescent response may include one or more characteristics
different from the first, previous and/or original target
fluorescent response, optionally as a result of the at least
partial ablation of the target. For example, the one or more
characteristics may include, but are not limited to, presence,
absence and/or reduction in the target fluorescent response.
[0269] An optional operation 960 includes an optional receiving
operation 962 and an optional determining operation 964. The
optional receiving operation 962 receives a third input associated
with a third possible dataset, the third possible dataset including
data representative of a fluorescent response. The optional
determining operation 964 determines data representative of one or
more characteristics of excitation energy 116 for inducing a target
fluorescent response at least partially based on the third possible
dataset. For example, data representative of a fluorescent response
may indicate the presence or absence of a target fluorescent
response.
[0270] Then, a providing operation 1060, provides a first output to
a first energy source in real time, the first output providing data
associated with at least partial ablation of a target at least
partially based on the first possible dataset. For example, data
representative of one or more characteristics of ablation energy
117, one or more characteristics of the excitation energy 116, one
or more characteristics of the fluorescent response, one or more
environmental parameters, and/or one or more targeting
parameters.
[0271] FIG. 10 and/or FIG. 11 depict embodiments of an operational
flow 700 representing illustrative embodiments of operations
related to providing a first output to a first energy source in
real time, the first output providing data representative of one or
more ablation characteristics for at least partially ablating a
target area. In FIG. 10 and/or FIG. 11, discussion and explanation
may be provided with respect to one or more apparatus 100 and/or
500 and/or device 200, 300 and/or 400 and methods described herein,
and/or with respect to other examples and contexts.
[0272] In some embodiments, one or more methods include receiving a
first input associated with a first possible dataset, the first
possible dataset including data representative of a target
fluorescent response; determining data representative of a location
of a target area at least partially based on the first possible
dataset; and providing a first output to a first energy source in
real time, the first output providing data representative of one or
more ablation characteristics for at least partially ablating the
target area.
[0273] In illustrative embodiments, operational flow 700 may be
employed in the process of target ablation to receive information
associated with a target fluorescent response optionally from one
or more apparatus 100 and/or 500 and/or devices 200, 300, and/or
400, optionally including, but not limited to, information relating
to the wavelength, intensity, strength, directionality, and/or
spatial extent of the fluorescent response. In illustrative
embodiments, operational flow 700 may be employed in the process of
target ablation to analyze information associated with a target
fluorescent response to determine data associated with the location
of a target and one or more characteristics of one or more energy
source 110 and/or ablation energy 117 associated with at least
partially ablating one or more target.
[0274] After a start operation, the operational flow 700 moves to a
receiving operation 170, receiving a first input associated with a
first possible dataset, the first possible dataset including data
representative of one or more target fluorescent response. For
example, a first input may include, but is not limited to, data
representative of one or more wavelengths of excitation energy,
direction, pulse time, timing, as well as detection wavelengths and
timing. For example, a first input may include, but is not limited
to, a condition, an illness, a cell and/or tissue type under
investigation, and/or other disease and/or preventive medicine
information An optional accessing operation 270 accesses the first
possible dataset in response to the first input. For example, data
representative of one or more fluorescent responses, one or more
autofluorescent responses, and/or one or more target fluorescent
responses may be accessed. For example, data representative of
background fluorescence, fluorescent tags and/or markers, and/or
limits of detection may be accessed.
[0275] An optional generating operation 370 generates the first
possible dataset in response to the first input. For example, data
representative of one or more target fluorescent response may be
generated optionally by eliminating and/or controlling for
endogenous non-target fluorescence and/or non-specific
fluorescence. For example, data representative of emissions as a
function of wavelength in relation to time and/or distance may be
generated.
[0276] An optional determining operation 470 determines a graphical
illustration of the first possible dataset. For example, data
representative of one or more fluorescent responses, one or more
autofluorescent responses, and/or one or more target fluorescent
response may be graphically represented. For example, data
representative of possible results associated with (and/or
corresponding to) one or more possible ablation parameters,
optionally including use of particle beam and/or electromagnetic
energy for target ablation, optionally in relation to other
non-target areas and/or the likelihood of collateral damage may be
graphically represented.
[0277] An optional determining operation 570 determining data
representative of a location of one or more target area at least
partially based on the first possible dataset. For example, data
representative of a location of one or more target area may
include, but is not limited to, direction, spatial extent,
environment, and/or depth, optionally in relation to one or more
excitation energy source 116, one or more targeting energy source
118, and/or one or more ablation energy source 117.
[0278] An optional sending operation 670 sends the first output
associated with the first possible dataset optionally to the first
energy source, optionally the ablation energy source 117. For
example, data representative of one or more target fluorescent
response, one or more characteristics of ablation energy 117,
and/or one or more targeting parameters may be sent as part of the
first output.
[0279] An optional determining operation 770 determines data
representative of one or more characteristics of excitation energy
116 for inducing the target fluorescent response. For example, data
representative of one or more characteristics of excitation energy
116, optionally including, but not limited to, wavelength,
strength, mode, directionality, and/or spatial limitations may be
determined.
[0280] An optional determining operation 870 determines data
representative of one or more characteristics of ablation energy
117 for at least partially ablating a target. For example, data
representative of one or more characteristics of ablation energy
117, optionally including, but not limited to, wavelength,
strength, mode, directionality, and/or spatial limitations may be
determined.
[0281] An optional operation 970 includes an optional receiving
operation 972 and an optional determining operation 974. The
optional receiving operation 972 receives a second input associated
with a second possible dataset, the second possible dataset
including data representative of a second target fluorescent
response following the at least partial ablation of the target. The
optional determining operation 974 determines data representative
of one or more characteristics of ablation energy 117 for further
ablating a target at least partially based on the second possible
dataset. For example, data representative of a second target
fluorescent response may include one or more characteristics
different from the first, previous and/or original target
fluorescent response, optionally as a result of the at least
partial ablation of the target. For example, the one or more
characteristics may include, but are not limited to, presence,
absence and/or extent of reduction in the target fluorescent
response.
[0282] An optional operation 1070 includes an optional receiving
operation 1072 and an optional determining operation 1074. The
optional receiving operation 1072 receives a third input associated
with a third possible dataset, the third possible dataset including
data representative of a fluorescent response. The optional
determining operation 1074 determines data representative of one or
more characteristics of excitation energy 116 for inducing a target
fluorescent response at least partially based on the third possible
dataset. For example, data representative of a fluorescent response
may indicate the presence, absence, or extent of reduction of a
target fluorescent response.
[0283] Then, a providing operation 1170, provides a first output to
a first energy source in real time, the first output providing data
representative of one or more ablation characteristics for at least
partially ablating the target area. For example, data
representative of one or more characteristics of ablation energy
117, one or more characteristics of the excitation energy 116, one
or more characteristics of the fluorescent response, one or more
environmental parameters, and/or one or more targeting
parameters.
[0284] FIG. 12 and/or FIG. 13 depict embodiments of an operational
flow 800 representing illustrative embodiments of operations
related to providing a first possible output to a first motive
source, the first possible output providing data representative of
one or more parameters associated with movement of an untethered
device in a lumen at least partially based on the location of the
target area. In FIG. 12 and/or FIG. 13, discussion and explanation
may be provided with respect to one or more device 200 and/or 300
and methods described herein, and/or with respect to other examples
and contexts.
[0285] In some embodiments, one or more methods include receiving a
first input associated with a first possible dataset, the first
possible dataset including data representative of a fluorescent
response; determining data representative of a location of a target
area at least partially based on the first possible dataset; and
providing a first possible output to a first motive source, the
first possible output providing data representative of one or more
parameters associated with movement of an untethered device in a
lumen at least partially based on the location of the target
area.
[0286] In illustrative embodiments, operational flow 800 may be
employed in the process of moving an untethered device in a lumen,
optionally associated with target ablation, to receive information
associated with a fluorescent response optionally from one or more
devices 200 and/or 300, optionally including, but not limited to,
information relating to the wavelength, intensity, strength,
directionality, and/or spatial extent of the fluorescent response.
In illustrative embodiments, operational flow 800 may be employed
in the process of moving an untethered device in a lumen to analyze
information associated with a target fluorescent response to
determine data associated with the location of a target and one or
more characteristics of one or more power source 140 and/or motive
force, optionally associated with at least partially ablating one
or more target.
[0287] After a start operation, the operational flow 800 moves to a
receiving operation 180, receiving a first input associated with a
first possible dataset, the first possible dataset including data
representative of one or more fluorescent response. For example,
data representative of one or more fluorescent response may
include, but is not limited to, data representative of a target
fluorescent response, a non-target fluorescent response, and/or a
autofluorescent response. For example, a first input may include,
but is not limited to, one or more characteristics of excitation
energy, one or more characteristics of targeting energy, and/or one
or more characteristics of ablation energy.
[0288] An optional accessing operation 280 accesses the first
possible dataset in response to the first input. For example, data
representative of one or more fluorescent responses, optionally
data representative of one or more target fluorescent response
and/or one or more autofluorescent response, may be accessed. For
example, data representative of the presence and/or absence of a
target fluorescent response and/or presence or absence of other
non-target fluorescent responses may be accessed.
[0289] An optional generating operation 380 generates the first
possible dataset in response to the first input. For example, data
representative of one or more target fluorescent response may be
generated optionally based on calculations associated with
background fluorescent, signal to noise ratios, non-specific
fluorescence, and/or endogenous non-target autofluoresce. For
example, data representative of a location of a target area
determined at least partially based on the fluorescent response may
also be generated.
[0290] An optional determining operation 480 determines a graphical
illustration of the first possible dataset. For example, data
representative of one or more target fluorescent response may be
graphically represented. For example, data representative of a
location of one or more target area optionally in relation to the
current device location may be graphically represented. For
example, data representative of one or more parameters associated
with the movement of the untethered device associated with target
ablation and/or target detection may be determined and/or
generated.
[0291] A determining operation 580 determines data representative
of a location of one or more target area at least partially based
on the first possible dataset. For example, data representative of
a location of one or more target area may include, but is not
limited to, direction, spatial extent, environment, and/or depth,
optionally in relation to one or more excitation energy source 116,
one or more targeting energy source 118, and/or one or more
ablation energy source 117. For example, data representative of a
location of one or more target area may include, but is not limited
to, one or more characteristics associated with movement of an
untethered device for target ablation and/or target detection.
[0292] An optional generating operation 680 generates the first
possible output in response to the first input. For example, a
first possible output may include data representative of a location
of one or more target area at least partially based on the first
possible dataset. For example, a first possible output may include,
but is not limited to, data representative of a direction of
movement, a rate of movement, a speed of movement, a time of
movement, a mechanism of movement, and/or a power source.
[0293] An optional sending operation 780 sends the first output
associated with the first possible dataset optionally to a motive
source 150 and/or a power source 140. For example, data
representative of a direction of movement, a rate of movement, a
speed of movement, a time of movement, a mechanism of movement,
and/or a power source may be sent as part of the first output.
[0294] An optional determining operation 880 determines data
representative of one or more characteristics of excitation energy
116 for inducing the fluorescent response. For example, data
representative of one or more characteristics of excitation energy
116, optionally including, but not limited to, wavelength,
strength, mode, directionality, and/or spatial limitations may be
determined.
[0295] An optional determining operation 980 determines data
representative of one or more characteristics of ablation energy
117 for at least partially ablating a target. For example, data
representative of one or more characteristics of ablation energy
117, optionally including, but not limited to, wavelength,
strength, mode, directionality, and/or spatial limitations may be
determined.
[0296] Then, a providing operation 1080, provides a first possible
output to a first motive source, the first possible output
providing data representative of one or more parameters associated
with movement of an untethered device in a lumen at least partially
based on the location of the target area. For example, data
representative of one or more characteristics of ablation energy
117, one or more characteristics of the excitation energy 116, one
or more characteristics of the fluorescent response, one or more
environmental parameters, and/or one or more targeting
parameters.
[0297] The following include illustrative embodiments of one or
more operations of operational flow 600, operational flow 700
and/or operational flow 800.
[0298] In illustrative embodiments, a target fluorescent response
is optionally an auto-fluorescent response and/or elicited from one
or more extrinsically provided markers.
[0299] In illustrative embodiments, a first input is from a sensor
configured to detect one or more of a target fluorescent response,
a fluorescent response, and/or an autofluorescent response. In
illustrative embodiments, a first input is from one or more
external sources, optionally remotely, programmably, and/or
wirelessly received. The one or more external sources may include,
but are not limited to, sensors, control circuitry, databases,
and/or user interfaces.
[0300] In illustrative embodiments, a first input includes data
representative of one or more measurements of electromagnetic
energy. One or more measurements of electromagnetic energy
optionally include, but are not limited to, one or more
measurements of one or more wavelengths of the electromagnetic
energy and/or measurements of an extended-spectrum of the
electromagnetic energy. One or more measurements of electromagnetic
energy optionally include, but are not limited to, measurements
over a cumulative time interval and/or time dependent
electromagnetic energy measurements. One or more time dependent
measurements may include, but are not limited to, measurements at
one or more times and/or measurements at one or more time intervals
following excitation of a fluorescent response. One or more
measurements of electromagnetic energy optionally include, but are
not limited to, one or more measurements of the location of the
source and/or incidence of electromagnetic energy (e.g. a
fluorescent response, excitation energy 116, ablation energy 117,
and/or targeting energy 118). One or more measurements of the
location of the source and/or incidence of electromagnetic energy
include, but are not limited to, one or more measurements of a
direction of incidence electromagnetic energy, and/or one or more
measurements of a tissue depth of incidence electromagnetic energy.
One or more measurements of electromagnetic energy optionally
include, but are not limited to, one or more measurements of a
strength of the electromagnetic energy.
[0301] In illustrative embodiments, a first input includes dara
representative of one or more characteristics of one or more
targets and/or one or more diseases and/or disorders. In
illustrative embodiments, a first input includes data
representative of the target fluorescent response. Data
representative of the target fluorescent response may include, but
is not limited to, one or more measurements of electromagnetic
energy, and/or one or more measurements of one or more
temporal-spatial locations of the target fluorescent response. As
used herein, the term "temporal-spatial locations" may include one
or more temporal locations and/or one or more spatial locations.
Data representative of a target fluorescent response may include,
but is not limited to, a clustering of fluorescent responses that
would otherwise be considered a normal response in the absence of
clustering, or with limited clustering, or non-significant
clustering. In illustrative embodiments, clustering might include
cells forming a plaque, bacterial cells forming a colony, blood
cells forming a clot, malaria-infected red blood cells aggregating,
among others.
[0302] In illustrative embodiments, a first possible dataset
includes data representative of one or more fluorescence
characteristics of one or more possible constituents of the target
area. As used herein, the term "constituents" may include, but is
not limited to, cells, tissues, lumen, proteins, plaques,
membranes, pathogens, microorganisms, and/or parasites, among
others.
[0303] In illustrative embodiments, a first possible dataset
includes data representative of one or more numerical measurements
for one or more possible constituents of the target area. One or
more numerical measurements may include, but are not limited to,
one or more numerical measurements for normal levels of one or more
possible constituents of the target area and/or for abnormal levels
of one or more possible constituents of the target area.
[0304] In illustrative embodiments, a first possible dataset
includes data representative of excitation energy 116. Data
representative of excitation energy 116 includes, but is not
limited to, data representative of one or more characteristics of
excitation energy 116. Data representative of one or more
characteristics of excitation energy 116 include, but are not
limited to, strength of the excitation energy, one or more
wavelengths of the excitation energy, one or more spatial
parameters of the excitation energy, and/or one or more directional
parameters of the excitation energy. One or more spatial parameters
of the excitation energy include, but are not limited to, one or
more spatial limitations of the excitation energy, optionally
including, but not limited to, spatially focused and spatially
collimated. One or more directional parameters of the excitation
energy include, but are not limited to, directionally limited,
directionally varied and directionally variable.
[0305] One or more characteristics of the excitation energy
include, but are not limited to, manual, programmable, automatic,
remote-controlled, and feedback-control. In illustrative
embodiments, for example, subsequent excitation energy
characteristics may be determined based on one or more
characteristics of the fluorescent emissions associated with the
characteristics of the previous excitation energy selected. For
example, if the previous excitation energy induced a fluorescent
response with high background and/or non-specific emissions, or
without a target signal, a different excitation energy might be
selected. In illustrative embodiments, for example, excitation
energy may be at least partially determined by the location, and/or
as a result of a prior ablation.
[0306] In illustrative embodiments, a first possible dataset
includes data representative of ablation energy 117. Data
representative of ablation energy 117 optionally includes, but is
not limited to data representative of one or more characteristics
of the ablation energy 117. One or more characteristics of the
ablation energy include, but are not limited to, strength of the
ablation energy, one or more wavelengths of the ablation energy,
one or more spatial parameters of the ablation energy, and/or one
or more directional parameters of the ablation energy. One or more
spatial parameters of the ablation energy include, but are not
limited to, one or more spatial limitations of the ablation energy,
optionally including, but not limited to, spatially focused and
spatially collimated. One or more directional parameters of the
ablation energy include, but are not limited to, directionally
limited, directionally varied and directionally variable.
[0307] One or more characteristics of the ablation energy include,
but are not limited to, manual, programmable, automatic,
remote-controlled, and feedback-controlled. One or more
characteristics of the ablation energy include, but are not limited
to, the minimum energy associated with at least partially ablating
one or more target areas and/or one or more non-target areas. One
or more characteristics of the ablation energy include, but are not
limited to, the one or more characteristics of the optimum energy
associated with at least partially ablating one or more target
areas while minimizing and/or reducing the ablation of one or more
non-target areas (e.g. reducing collateral damage). In illustrative
embodiments, one or more characteristics of ablation energy may be
determined based on detection of only partial ablation from a prior
ablation.
[0308] In some embodiments, ablation energy 117 is one or more of
charged particles (e.g. from a particle beam) 112 or
electromagnetic energy 111. In some embodiments, particle beam
energy 112 may include, but is not limited to, electrons, protons,
alpha particles, beta particles and/or gamma particles. In some
embodiments, electromagnetic energy 111 may include, but is not
limited to, optical energy 113 and/or X-ray 115 energy. In some
embodiments, ablation energy 117 is pulsed energy.
[0309] In illustrative embodiments of a receiving operation 160,
170, and/or 180, receiving a first input associated with a first
possible dataset includes, but is not limited to, receiving a first
data entry associated with the first possible dataset. In
illustrative embodiments, a first data entry may include, but is
not limited to, one or more measurements of energy (optionally
electromagnetic energy) and/or one or more measurements of one or
more temporal-spatial locations of a fluorescent response (e.g. a
target fluorescent response). In illustrative embodiments, a first
data entry may include, but is not limited to, data representative
of one or more characteristics of one or more targets, one or more
diseases, and/or one or more disorders.
[0310] In illustrative embodiments of a receiving operation 160,
170, and/or 180, receiving a first input associated with a first
possible dataset includes, but is not limited to, receiving a first
data entry from a sensor, from a database, and/or from a user
interface (e.g. from at least one submission element of a graphical
user interface).
[0311] In illustrative embodiments of a receiving operation 160,
170, and/or 180, receiving a first input associated with a first
possible dataset includes, but is not limited to, receiving a first
data entry at least partially identifying one or more elements of
the first possible dataset. In illustrative embodiments, one or
more elements of the first possible dataset include one or more of
one or more measurements of electromagnetic energy, one or more
measurements of one or more temporal-spatial locations of a target
fluorescent response, data representative of excitation energy,
and/or data representative of ablation energy 117.
[0312] In illustrative embodiments of a receiving operation 160,
170, and/or 180, receiving a first input associated with a first
possible dataset includes, but is not limited to, receiving a first
request associated with the first possible dataset. In illustrative
embodiments, the first request includes, but is not limited to,
selecting and/or determining data representative of one or more
measurements of electromagnetic energy, data representative of one
or more measurements of one or more temporal-spatial locations of
the target fluorescent response, and/or data representative of one
or more characteristics of ablation energy.
[0313] In illustrative embodiments of a receiving operation 160,
170, and/or 180, receiving a first input associated with a first
possible dataset includes, but is not limited to, receiving a first
request from a user interface (e.g. at least one submission element
of a graphical user interface). In illustrative embodiments, the
first request at least partially identifies and/or selects one or
more elements of the first possible dataset. In illustrative
embodiments, the first request provides instructions identifying,
specifying, and/or determining data representative of one or more
elements of the first possible dataset.
[0314] In illustrative embodiments of an optional accessing
operation 260, 270, and/or 280 accessing the first possible dataset
in response to the first input includes, but is not limited to,
accessing the first possible dataset using a database management
system engine. In some embodiments, the database management system
engine is configured to query a first database to retrieve the
first possible dataset therefrom. In illustrative embodiments,
accessing the first possible dataset in response to the first input
includes, but is not limited to, accessing the first possible
dataset by querying a first database to retrieve data
representative of one or more characteristics of one or more
targets associated with one or more diseases and/or disorders.
[0315] In illustrative embodiments of an optional accessing
operation 260, 270, and/or 280 accessing the first possible dataset
in response to the first input includes, but is not limited to,
accessing the first possible dataset from within a first database
associated with a plurality of measurements of electromagnetic
energy, a plurality of measurements of one or more temporal-spatial
locations of the target fluorescent response, and/or a plurality of
characteristics of ablation energy.
[0316] In illustrative embodiments of an optional accessing
operation 260, 270, and/or 280 accessing the first possible dataset
in response to the first input includes, but is not limited to,
accessing the first possible dataset by associating data
representative of one or more measurements of electromagnetic
energy, data representative of one or more temporal-spatial
locations of the target fluorescent response, and/or data
representative of one or more characteristics of ablation energy
with one or more elements of the first possible dataset.
[0317] In illustrative embodiments of an accessing operation 260,
270, and/or 280 accessing the first possible dataset in response to
the first input includes, but is not limited to, accessing the
first possible dataset by corresponding data representative of one
or more measurements of electromagnetic energy, data representative
of one or more temporal-spatial locations of the target fluorescent
response, and/or data representative of one or more characteristics
of ablation energy with one or more elements of the first possible
dataset.
[0318] In illustrative embodiments of an accessing operation 260,
270, and/or 280 accessing the first possible dataset in response to
the first input includes, but is not limited to, accessing the
first possible dataset as being associated with data representative
one or more measurements of electromagnetic energy, data
representative of one or more measurements of one or more
temporal-spatial locations of the target fluorescent response,
and/or data representative of one or more characteristics of
ablation energy.
[0319] In illustrative embodiments of an optional generating
operation 360, 370, and/or 380, generating the first possible
dataset in response to the first input includes, but is not limited
to, generating the first possible dataset using a database
management system engine. In illustrative embodiments, generating
the first possible dataset in response to the first input includes,
but is not limited to, generating the first possible dataset using
a database management system engine to retrieve data representative
of one or more characteristics of one or more targets associated
with one or more diseases and/or disorders.
[0320] In illustrative embodiments of an optional generating
operation 360, 370, and/or 380, generating the first possible
dataset in response to the first input includes, but is not limited
to, generating the first possible dataset by corresponding and/or
associating data representative of one or more measurements of
electromagnetic energy, data representative of one or more
measurements of temporal-spatial locations of the target
fluorescent response, and/or data representative of one or more
characteristics of ablation energy with one or more elements of the
first possible dataset.
[0321] In illustrative embodiments of an optional generating
operation 360, 370, and/or 380, generating the first possible
dataset in response to the first input includes, but is not limited
to, receiving a first request associated with the first possible
dataset; and generating the first possible dataset in response to
the first request, the first request specifying data representative
of one or more measurements of electromagnetic energy, data
representative of one or more measurements of one or more
temporal-spatial locations of the target fluorescent response
and/or data representative of one or more characteristics of
ablation energy. In illustrative embodiments, the first request
specifies one or more characteristics of one or more targets.
[0322] In illustrative embodiments of an optional generating
operation 360, 370, and/or 380, generating the first possible
dataset in response to the first input includes, but is not limited
to, receiving a first request, the first request specifying data
representative of one or more measurements of electromagnetic
energy; and generating the first possible dataset in response to
the first request at least partially by performing an analysis of
data representative of one or more measurements of one or more
temporal-spatial locations of the target fluorescent response.
[0323] In illustrative embodiments of an optional generating
operation 360, 370, and/or 380, generating the first possible
dataset in response to the first input includes, but is not limited
to, receiving a first request, the first request specifying data
representative of one or more measurements of one or more
temporal-spatial locations of the target fluorescent response; and
generating the first possible dataset in response to the first
request at least partially by performing an analysis of data
representative of one or more measurements of electromagnetic
energy.
[0324] In illustrative embodiments of an optional generating
operation 360, 370, and/or 380, generating the first possible
dataset in response to the first input includes, but is not limited
to, receiving a first request, the first request specifying data
representative of one or more characteristics of ablation energy;
and generating the first possible dataset in response to the first
request at least partially by performing an analysis of data
representative of one or more measurements of electromagnetic
energy.
[0325] In illustrative embodiments of an optional generating
operation 360, 370, and/or 380, generating the first possible
dataset in response to the first input includes, but is not limited
to, receiving a first request, the first request specifying data
representative of one or more characteristics of ablation energy;
and generating the first possible dataset in response to the first
request at least partially by performing an analysis of data
representative one or more measurements of one or more
temporal-spatial locations of the target fluorescent response.
[0326] In illustrative embodiments of an optional determining
operation 460, 470, and/or 480, determining a graphical
illustration of the first possible dataset includes, but is not
limited to, determining the graphical illustration of the first
possible dataset for inclusion in a display element of a graphical
user interface. In illustrative embodiments, determining a
graphical illustration of the first possible dataset includes, but
is not limited to, determining a graphical illustration of data
representative of one or more characteristics of one or more
targets associated with one or more diseases and/or disorders.
[0327] In illustrative embodiments of an optional determining
operation 460, 470, and/or 480, determining a graphical
illustration of the first possible dataset includes, but is not
limited to, performing an analysis of one or more elements of the
first possible dataset to determine the location of the target
area; and determining the graphical illustration based on the
analysis.
[0328] In illustrative embodiments of an optional determining
operation 460, 470, and/or 480, determining a graphical
illustration of the first possible dataset includes, but is not
limited to, performing an analysis of one or more elements of the
first possible dataset to determine the location of the target
area; and determining the graphical illustration including data
representative of one or more measurements of electromagnetic
energy, data representative of one or more measurements of one or
more temporal-spatial locations of the target fluorescent response,
and/or data representative of one or more characteristics of
ablation energy in association with a visual indicator related to
the location of the target area.
[0329] In illustrative embodiments of an optional determining
operation 460, 470, and/or 480, determining a graphical
illustration of the first possible dataset includes, but is not
limited to, performing an analysis of one or more elements of the
first possible dataset to determine a first possible outcome; and
determining the graphical illustration based on the analysis. In
illustrative embodiments, the first possible outcome optionally
includes, but is not limited to, one or more of a possible risk, a
possible result, or a possible consequence.
[0330] In illustrative embodiments of an optional determining
operation 460, 470, and/or 480, determining a graphical
illustration of the first possible dataset includes, but is not
limited to, performing an analysis of one or more elements of the
first possible dataset to determine a first possible outcome; and
determining the graphical illustration including data
representative of one or more measurements of electromagnetic
energy, data representative of one or more measurements of one or
more temporal-spatial locations of the target fluorescent response,
and/or data representative of one or more characteristics of
ablation energy in association with a visual indicator related to
the first possible outcome.
[0331] In illustrative embodiments of an optional determining
operation 460, 470, and/or 480, determining a graphical
illustration of the first possible dataset includes, but is not
limited to, determining a correlation between a first possible
outcome and a type or characteristic of a visual indicator used in
the graphical illustration to represent the first possible
outcome.
[0332] In illustrative embodiments of an optional determining
operation 460, 470, and/or 480, determining a graphical
illustration of the first possible dataset includes, but is not
limited to, determining the graphical illustration of a first
possible outcome based on use of ablation energy having one or more
characteristics. A first possible outcome may include, but is not
limited to, partial ablation, complete ablation, non-target partial
ablation, and/or non-target complete ablation, among others.
[0333] In illustrative embodiments of a determining operation 570
and/or 580, determining data representative of a location of a
target area at least partially based on the first possible dataset
includes, but is not limited to, determining data representative of
the location of the target area at least partially based on the
first possible dataset, the first possible dataset including one or
more measurements of electromagnetic energy, and/or one or more
measurements of the target fluorescent response. In illustrative
embodiments, determining data representative of a location of a
target area at least partially based on the first possible dataset
includes, but is not limited to, determining data representative of
one or more characteristics of one or more targets associated with
one or more diseases and/or disorders.
[0334] In illustrative embodiments of a determining operation 570
and/or 580, determining data representative of a location of a
target area at least partially based on the first possible dataset
includes, but is not limited to, performing an analysis of one or
more elements of the first possible dataset; and determining data
representative of the location of the target area at least
partially based on the analysis. In illustrative embodiments,
analysis of the first possible dataset my include a determination
of coordinates for ablation, and/or a determination that one or
more target locations are not within range of ablation energy,
and/or a determination that ablation of one or more targets has a
possibility of causing non-target damage.
[0335] In illustrative embodiments of a determining operation 570
and/or 580, determining data representative of a location of a
target area at least partially based on the first possible dataset
includes, but is not limited to, performing an analysis of one or
more elements of the first possible dataset and at least one
additional instruction; and determining data representative of the
location of the target area at least partially based on the
analysis.
[0336] In illustrative embodiments of an optional generating
operation 680, generating the first possible output in response to
the first input includes, but is not limited to, generating the
first possible output at least partially based on information
associated with the location of a target and movement of an
untethered device associated with ablation. In illustrative
embodiments, one or more target is identified, optionally in a
location too distant and/or obstructed for ablation and one or more
parameters associated with movement of the untethered device to a
location optionally to facilitate ablation are generated. In
illustrative embodiments, no targets are identified in a particular
location and one or more parameters associated with movement of the
untethered device to another location optionally to facilitate
further screening are generated.
[0337] In illustrative embodiments of an optional sending operation
560, 670, and/or 780, sending a first output associated with the
first possible dataset includes, but is not limited to, sending a
first output to one or more of a motive source 150, a power source
140, and/or an energy source 110, optionally an excitation energy
source 116 and/or an ablation energy source 117. In some
embodiments, sending a first output associated with the first
possible dataset includes, but is not limited to, sending a first
output to one or more external sources, optionally to one or more
control circuitry 130, optionally in an external and/or remote
location, that optionally provide a graphical illustration of the
output, and/or that provide analysis and feedback at least
partially based on the output.
[0338] In illustrative embodiments of an optional determining
operation 660, 770, and/or 880, determining data representative of
one or more characteristics of excitation energy 116 for inducing
the target fluorescent response includes, but is not limited to,
determining one or more characteristics of excitation energy 116
based at least partially on one or more of, but not limited to, the
location of the lesion, the lumen, and/or the internal location,
the environmental characteristics of the location, the distance,
depth of tissue, and putative target, as well as the
characteristics of the expected surrounding constituents.
[0339] In illustrative embodiments, one or more characteristics of
the excitation energy 116 include, but are not limited to, one or
more of strength of the excitation energy, wavelengths of the
excitation energy, spatial parameters of the excitation energy,
and/or directional parameters of the excitation energy. In some
embodiments, one or more spatial parameters of the excitation
energy include, but are not limited to, one or more spatial
limitations of the excitation energy and/or a depth of focus of the
excitation energy. In some embodiments, one or more spatial
limitations include, but are not limited to, spatially focused and
spatially collimated. In some embodiments, one or more
characteristics of the depth of focus of the excitation energy
includes, but are not limited to, a depth of focus is below a
surface of a lesion, beyond a surface of a wall of a lumen, and/or
beyond a surface of an internal location. In illustrative
embodiments, a depth of focus is approximately 0.1 mm to 3 mm below
a surface of a lesion, beyond a surface of a wall of a lumen,
and/or beyond a surface of an internal location. In some
embodiments, one or more directional parameters include, but are
not limited to, directionally limited, directionally varied and
directionally variable.
[0340] In illustrative embodiments, one or more characteristics of
the excitation energy 116 include, but are not limited to, manual,
programmable, automatic, remote-controlled, and
feedback-controlled. In illustrative embodiments, a care-giver
(physician, veterinarian, dentist, etc.) makes the final
determination for ablation based on information determined by one
or more program, and manually releases the programmably determined
ablation energy.
[0341] In illustrative embodiments, excitation energy 116 is
electromagnetic energy, optionally optical energy. In illustrative
embodiments, excitation energy 116 is pulsed energy. In
illustrative embodiments, excitation energy 116 is optionally
single photon electromagnetic energy, two photon electromagnetic
energy, multiple wavelength electromagnetic energy, and/or
extended-spectrum electromagnetic energy. In some embodiments, two
photon electromagnetic energy is coupled through a virtual energy
level and/or through an intermediate energy level. In some
embodiments, two photon electromagnetic energy is generated by two
photons having the same wavelength or by two photons having a
different wavelength.
[0342] In Illustrative embodiments of an optional determining
operation 760, 870, and/or 980, determining data representative of
one or more characteristics of ablation energy for at least
partially ablating the target area includes, but is not limited to,
assessing one or more characteristics of one or more constituents,
assessing one or more characteristics of the target (e.g. location,
size, depth, distance, etc.), and/or selecting one or more energy
sources. In illustrative embodiments, the one or more
characteristics of the ablation energy are selected to optimally
ablate the target area while minimizing ablation outside the target
area.
[0343] In illustrative embodiments, optional receiving and
determining operations 860 and/or 970 include receiving a second
input associated with a second possible dataset, the second
possible dataset including data representative of a second target
fluorescent response following at least partial ablation of the
target area; and determining data representative of one or more
characteristics of ablation energy for further ablating the target
area at least partially based on the second possible dataset. In
illustrative embodiments, excitation energy is optionally provided
following at least partial ablation of one or more target
optionally to determine the extent of ablation of target and/or
non-target tissues and/or cells. Emission information detected by
one or more sensor is optionally used to determine locations
(optionally coordinates) for additional ablation, as necessary.
[0344] In illustrative embodiments, optional receiving and
determining operations 960 and/or 1070 include receiving a third
input associated with a third possible dataset, the third possible
dataset including data representative of a fluorescent response;
and determining data representative of one or more characteristics
of excitation energy for inducing the target fluorescent response
at least partially based on the third possible dataset. In
illustrative embodiments, excitation energy of one or more
characteristics may not elicit an identifiable and/or detectable
target fluorescent response by the sensor. At least partially based
on the lack of detection of a target fluorescent response (and the
characteristics of the excitation energy released), characteristics
of an additional excitation energy for release are selected, and
optionally provided to the electromagnetic energy source 111,
optionally one or more excitation energy source 116.
[0345] In illustrative embodiments of a providing operation 1060
and/or 1170, providing a first output to a first energy source in
real time includes, but is not limited to, sending the first output
to the first energy source in real time.
[0346] In illustrative embodiments of a providing operation 1060
and/or 1170, providing a first output to a first energy source in
real time includes, but is not limited to, sending a first
instruction associated with the first possible dataset to the first
energy source. In illustrative embodiments, the first instruction
contains data representative of one or more measurements of
electromagnetic energy, data representative of one or more
measurements of target fluorescent energy, data representative of
one or more characteristics of ablation energy, data representative
of one or more characteristics of targeting energy, and/or data
representative of the location of the target area to be at least
partially ablated.
[0347] In illustrative embodiments of a providing operation 1060
and/or 1170, providing a first output to a first energy source in
real time includes, but is not limited to, sending the first output
to the first targeting energy source in real time, the first output
providing data representative of the one or more ablation
characteristics for at least partially ablating the target
area.
[0348] In illustrative embodiments, a first energy source 110 is an
electromagnetic energy source 111, optionally an optical energy
source 113 and/or an X-ray energy source 115. In some embodiments,
the first energy source 110 is a laser. In illustrative
embodiments, a first energy source 110 is a charged particle source
112 that optionally provides particles including, but not limited
to, electrons, protons, alpha particles, beta particles, and/or
gamma particles.
[0349] In illustrative embodiments, a first output includes data
representative of one or more characteristics of ablation energy
117 for at least partially ablating the target area. In
illustrative embodiments, ablation energy 117 is electromagnetic
energy and/or charged particles. In illustrative embodiments, a
first output includes targeting data for at least partially
ablating the target area. In illustrative embodiments, a first
output includes data representative of the location of the target
area to be at least partially ablated.
[0350] In illustrative embodiments, a first targeting energy 118
has a different spatial irradiation extent than the first energy
source 110. in some embodiments, the first targeting energy source
provides electromagnetic targeting energy, optionally optical
targeting energy, optionally visual targeting energy.
[0351] In illustrative embodiments of a providing operation 1080,
providing a first output to a first motive source includes, but is
not limited to, providing a first output to a first motive source
in real time. In illustrative embodiments of a providing operation
1080, providing a first output to a first motive source includes,
but is not limited to, sending the first output to the first motive
source optionally in real time.
[0352] The following provides a description of illustrative
computer program products 1200, 1300, and/or 1400 based on one or
more of the operational flows 600, 700, and/or 800 and variations
thereof as described above. These computer program products may
also be executed in a variety of other contexts and environments,
and or in modified versions of those described herein. In addition,
although some of the computer program products are presented in
sequence, the various instructions may be performed in various
repetitions, concurrently, and/or in other orders than those that
are illustrated. Although instructions for several computer program
products are described separately herein, these instructions may be
performed in sequence, in various repetitions, concurrently, and in
a variety of orders not specifically illustrated herein. In
addition, one or more of the instructions described for one or more
computer program products may be added to another computer program
product and/or used to replace one or more instructions in the
computer program products, with or without deletion of one or more
instructions of the computer program products.
[0353] FIG. 14 and FIG. 15 show a schematic of a partial view of an
illustrative computer program product 1200 that includes a computer
program for executing a computer process on a computing device. An
illustrative embodiment of the illustrative computer program
product is provided using a signal bearing medium 1210, and may
include at least one of one or more instructions 1215 including:
one or more instructions for receiving a first input associated
with a first possible dataset, the first possible dataset including
data representative of a target fluorescent response; one or more
instructions for accessing the first possible dataset in response
to the first input; one or more instructions for generating the
first possible dataset in response to the first input; one or more
instructions for determining a graphical illustration of the first
possible dataset; one or more instructions for sending the first
output associated with the first possible dataset; one or more
instructions for determining data representative of one or more
characteristics of excitation energy for inducing the target
fluorescent response; one or more instructions for determining data
representative of one or more characteristics of ablation energy
for at least partially ablating a target; one or more instructions
for receiving a second input associated with a second possible
dataset, the second possible dataset including data representative
of a second target fluorescent response following at least partial
ablation of a target; one or more instructions for determining data
representative of one or more characteristics of ablation energy
for further ablating a target at least partially based on the
second possible dataset; one or more instructions for receiving a
third input associated with a third possible dataset, the third
possible dataset including data representative of a fluorescent
response; one or more instructions for determining data
representative of one or more characteristics of excitation energy
for inducing the target fluorescent response at least partially
based on the third possible dataset; one or more instructions for
providing a first output to a first energy source in real time, the
first output providing data associated with at least partial
ablation of a target at least partially based on the first possible
dataset. The one or more instructions may be, for example, computer
executable and/or logic implemented instructions. In some
embodiments, the signal bearing medium 1210 of the one or more
computer program products 1200 include a computer-readable medium
1220, a recordable medium 1230, and/or a communications medium
1240.
[0354] FIG. 16 and FIG. 17 show a schematic of a partial view of an
illustrative computer program product 1300 that includes a computer
program for executing a computer process on a computing device. An
illustrative embodiment of the illustrative computer program
product is provided using a signal bearing medium 1310, and may
include at least one of one or more instructions 1315 including:
one or more instructions for receiving a first input associated
with a first possible dataset, the first possible dataset including
data representative of a target fluorescent response; one or more
instructions for accessing the first possible dataset in response
to the first input; one or more instructions for generating the
first possible dataset in response to the first input; one or more
instructions for determining a graphical illustration of the first
possible dataset; one or more instructions for determining data
representative of a location of a target area at least partially
based on the first possible dataset; one or more instructions for
sending the first output associated with the first possible
dataset; one or more instructions for determining data
representative of one or more characteristics of excitation energy
for inducing the target fluorescent response; one or more
instructions for determining data representative of one or more
characteristics of ablation energy for at least partially ablating
a target; one or more instructions for receiving a second input
associated with a second possible dataset, the second possible
dataset including data representative of a second target
fluorescent response following at least partial ablation of a
target; one or more instructions for determining data
representative of one or more characteristics of ablation energy
for further ablating a target at least partially based on the
second possible dataset; one or more instructions for receiving a
third input associated with a third possible dataset, the third
possible dataset including data representative of a fluorescent
response; one or more instructions for determining data
representative of one or more characteristics of excitation energy
for inducing the target fluorescent response at least partially
based on the third possible dataset; one or more instructions for
providing a first output to a first energy source in real time, the
first output providing data representative of one or more ablation
characteristics for at least partially ablating the target area.
The one or more instructions may be, for example, computer
executable and/or logic implemented instructions. In some
embodiments, the signal bearing medium 1310 of the one or more
computer program products 1300 include a computer-readable medium
1320, a recordable medium 1330, and/or a communications medium
1340.
[0355] FIG. 18 and FIG. 19 show a schematic of a partial view of an
illustrative computer program product 1400 that includes a computer
program for executing a computer process on a computing device. An
illustrative embodiment of the illustrative computer program
product is provided using a signal bearing medium 1410, and may
include at least one of one or more instructions 1415 including:
one or more instructions for receiving a first input associated
with a first possible dataset, the first possible dataset including
data representative of a fluorescent response; one or more
instructions for accessing the first possible dataset in response
to the first input; one or more instructions for generating the
first possible dataset in response to the first input; one or more
instructions for determining a graphical illustration of the first
possible dataset; one or more instructions for determining data
representative of a location of a target area at least partially
based on the first possible dataset; one or more instructions for
generating the first possible output in response to the first
input; one or more instructions for sending the first output
associated with the first possible dataset; one or more
instructions for determining data representative of one or more
characteristics of excitation energy for inducing the target
fluorescent response; one or more instructions for determining data
representative of one or more characteristics of ablation energy
for at least partially ablating a target; one or more instructions
for providing a first possible output to a first motive source, the
first possible output providing data representative of one or more
parameters associated with movement of an untethered device in a
lumen at least partially based on the location of the target area.
The one or more instructions may be, for example, computer
executable and/or logic implemented instructions. In some
embodiments, the signal bearing medium 1410 of the one or more
computer program products 1400 include a computer-readable medium
1420, a recordable medium 1430, and/or a communications medium
1440.
[0356] The following provides a description of illustrative systems
based on one or more of the operational flows 600, 700, and/or 800
and/or computer program products 1200, 1300, and/or 1400 and/or
variations thereof as described above. These systems may also be
executed in a variety of other contexts and environments, and or in
modified versions of those described herein.
[0357] FIG. 20 and FIG. 21 show a schematic of an illustrative
system 1500 in which embodiments may be implemented. In some
embodiments, system 1500 may be the same as system 1600 and/or
system 1700. In some embodiments, system 1500 may be different from
system 1600 and/or system 1700. System 1500 may include a computing
system environment 1510. System 1500 also illustrates an operator
1501 (e.g. a medical or veterinary professional, optionally a
surgeon, a veterinarian, a nurse, a technician, etc.) using a
device 1540 that is optionally shown as being in communication with
a computing device 1520 by way of an optional coupling 1545. The
optional coupling may represent a local, wide area, or peer-to-peer
network, or may represent a bus that is internal to a computing
device (e.g. in illustrative embodiments the computing device 1520
is contained in whole or in part within the device 1510, 1540, 200,
300, and/or 400 or within one or more apparatus 100 and/or 500, or
one or more control circuitry 130). An optional storage medium 1525
may be any computer storage medium.
[0358] The computing device 1520 includes one or more computer
executable instructions 1530 that when executed on the computing
device 1520 cause the computing device 1520 receive a first input
associated with a first possible dataset, the first possible
dataset including data representative of a target fluorescent
response; access the first possible dataset in response to the
first input; generate the first possible dataset in response to the
first input; determine a graphical illustration of the first
possible dataset; send the first output associated with the first
possible dataset; determine data representative of one or more
characteristics of excitation energy for inducing the target
fluorescent response; determine data representative of one or more
characteristics of ablation energy for at least partially ablating
a target; receive a second input associated with a second possible
dataset, the second possible dataset including data representative
of a second target fluorescent response following at least partial
ablation of a target; determine data representative of one or more
characteristics of ablation energy for further ablating a target at
least partially based on the second possible dataset; receive a
third input associated with a third possible dataset, the third
possible dataset including data representative of a fluorescent
response; determine data representative of one or more
characteristics of excitation energy for inducing the target
fluorescent response at least partially based on the third possible
dataset; provide a first output to a first energy source in real
time, the first output providing data associated with at least
partial ablation of a target at least partially based on the first
possible dataset. In some illustrative embodiments, the computing
device 1520 may optionally be contained in whole or in part within
one or more parts of an apparatus 100 and/or 500 and/or one or more
devices 200, 300, and/or 400 (e.g. control circuitry 130 of one or
more tethered and/or untethered, internal and/or external, movable
and/or fixed apparatus and/or device), or may optionally be
contained in whole or in part within the operator device 1540.
[0359] The system 1500 includes at least one computing device 1510,
1520, 1540 and/or control circuitry 130 on which the
computer-executable instructions 1530 may be executed. For example,
one or more of the computing devices 1510, 1520, 1540 and/or
control circuitry 130 may execute the one or more computer
executable instructions 1530 and output a result and/or receive
information from the operator 1501, from other external sources,
and/or from one or more sensor 120, on the same or a different
computing device 1510, 1520, 1540, 1610, 1620, 1640, 1710, 1720,
and/or 1740 and/or output a result and/or receive information from
one or more apparatus 100 and/or 500 and/or one or more device 200,
300 and/or 400 in order to perform and/or implement one or more of
the techniques, processes, or methods described herein, and/or
other techniques.
[0360] The computing device 1510, 1520, and/or 1540 may include one
or more of a desktop computer, a workstation computer, a computing
system comprised a cluster of processors, a networked computer, a
tablet personal computer, a laptop computer, or a personal digital
assistant, or any other suitable computing unit. In some
embodiments, any one of the one or more computing devices 1510,
1520, and/or 1540 and/or control circuitry 130 may be operable to
communicate with a database to access the first possible dataset
and/or subsequent datasets. In some embodiments, the computing
device 1510, 1520, and/or 1540 is operable to communicate with the
one or more apparatus 100 and/or 500 and/or device 200, 300, and/or
400 (e.g. control circuitry 130).
[0361] FIG. 22 and FIG. 23 show a schematic of an illustrative
system 1600 in which embodiments may be implemented. In some
embodiments, system 1600 may be the same as system 1500 and/or
system 1700. In some embodiments, system 1600 may be different from
system 1500 and/or system 1700. System 1600 may include a computing
system environment 1510. System 1600 also illustrates an operator
1501 (e.g. a medical or veterinary professional, optionally a
surgeon, a veterinarian, a nurse, a technician, etc.) using a
device 1540 that is optionally shown as being in communication with
a computing device 1620 by way of an optional coupling 1545. An
optional storage medium 1525 may be any computer storage
medium.
[0362] The computing device 1620 includes one or more computer
executable instructions 1630 that when executed on the computing
device 1620 cause the computing device 1620 to receive a first
input associated with a first possible dataset, the first possible
dataset including data representative of a target fluorescent
response; access the first possible dataset in response to the
first input; generate the first possible dataset in response to the
first input; determine a graphical illustration of the first
possible dataset; determine data representative of a location of a
target area at least partially based on the first possible dataset;
send the first output associated with the first possible dataset;
determine data representative of one or more characteristics of
excitation energy for inducing the target fluorescent response;
determine data representative of one or more characteristics of
ablation energy for at least partially ablating a target; receive a
second input associated with a second possible dataset, the second
possible dataset including data representative of a second target
fluorescent response following at least partial ablation of a
target; determine data representative of one or more
characteristics of ablation energy for further ablating a target at
least partially based on the second possible dataset; receive a
third input associated with a third possible dataset, the third
possible dataset including data representative of a fluorescent
response; determine data representative of one or more
characteristics of excitation energy for inducing the target
fluorescent response at least partially based on the third possible
dataset; provide a first output to a first energy source in real
time, the first output providing data representative of one or more
ablation characteristics for at least partially ablating the target
area.
[0363] In some illustrative embodiments, the computing device 1620
may optionally be contained in whole or in part within one or more
parts of an apparatus 100 and/or 500 and/or one or more devices
200, 300, and/or 400 (e.g. control circuitry 130 of one or more
tethered and/or untethered, internal and/or external, movable
and/or fixed apparatus and/or device), or may optionally be
contained in whole or in part within the operator device 1540.
[0364] The system 1600 includes at least one computing device 1510,
1620, 1540 and/or control circuitry 130 on which the
computer-executable instructions 1630 may be executed. For example,
one or more of the computing devices 1510, 1620, 1540 and/or
control circuitry 130 may execute the one or more computer
executable instructions 1630 and output a result and/or receive
information from the operator 1501, from other external sources,
and/or from one or more sensor 120, on the same or a different
computing device 1510, 1520, 1540, 1620, and/or 1720 and/or output
a result and/or receive information from one or more apparatus 100
and/or 500 and/or one or more device 200, 300 and/or 400 in order
to perform and/or implement one or more of the techniques,
processes, or methods described herein, and/or other
techniques.
[0365] The computing device 1510, 1620, 1540 may include one or
more of a desktop computer, a workstation computer, a computing
system comprised a cluster of processors, a networked computer, a
tablet personal computer, a laptop computer, or a personal digital
assistant, or any other suitable computing unit. In some
embodiments, any one of the one or more computing devices 1510,
1620, and/or 1540 and/or control circuitry 130 may be operable to
communicate with a database to access the first possible dataset
and/or subsequent datasets. In some embodiments, the computing
device 1510, 1620, and/or 1540 is operable to communicate with the
one or more apparatus 100 and/or 500 and/or device 200, 300, and/or
400 (e.g. control circuitry 130).
[0366] FIG. 24 and FIG. 25 show a schematic of an illustrative
system 1700 in which embodiments may be implemented. In some
embodiments, system 1700 may be the same as system 1500 and/or
system 1600. In some embodiments, system 1700 may be different from
system 1500 and/or system 1600. System 1700 may include a computing
system environment 1510. System 1700 also illustrates an operator
1501 (e.g. a medical or veterinary professional, optionally a
surgeon, a veterinarian, a nurse, a technician, etc.) using a
device 1540 that is optionally shown as being in communication with
a computing device 1720 by way of an optional coupling 1545. An
optional storage medium 1525 may be any computer storage
medium.
[0367] The computing device 1720 includes one or more computer
executable instructions 1730 that when executed on the computing
device 1720 cause the computing device 1720 receive a first input
associated with a first possible dataset, the first possible
dataset including data representative of a fluorescent response;
access the first possible dataset in response to the first input;
generate the first possible dataset in response to the first input;
determine a graphical illustration of the first possible dataset;
determine data representative of a location of a target area at
least partially based on the first possible dataset; generate the
first possible output in response to the first input; send the
first output associated with the first possible dataset; determine
data representative of one or more characteristics of excitation
energy for inducing the target fluorescent response; determine data
representative of one or more characteristics of ablation energy
for at least partially ablating a target; provide a first possible
output to a first motive source, the first possible output
providing data representative of one or more parameters associated
with movement of an untethered device in a lumen at least partially
based on the location of the target area.
[0368] In some illustrative embodiments, the computing device 1720
may optionally be contained in whole or in part within one or more
parts of an apparatus 100 and/or 500 and/or one or more devices
200, 300, and/or 400 (e.g. control circuitry 130 of one or more
tethered and/or untethered, internal and/or external, movable
and/or fixed apparatus and/or device), or may optionally be
contained in whole or in part within the operator device 1540.
[0369] The system 1700 includes at least one computing device 1510,
1720, 1540 and/or control circuitry 130 on which the
computer-executable instructions 1730 may be executed. For example,
one or more of the computing devices 1510, 1720, 1540 and/or
control circuitry 130 may execute the one or more computer
executable instructions 1730 and output a result and/or receive
information from the operator 1501, from other external sources,
and/or from one or more sensor 120, on the same or a different
computing device 1510, 1520, 1540, 1620, and/or 1720 and/or output
a result and/or receive information from one or more apparatus 100
and/or 500 and/or one or more device 200, 300 and/or 400 in order
to perform and/or implement one or more of the techniques,
processes, or methods described herein, and/or other
techniques.
[0370] The computing device 1510, 1720, 1540 may include one or
more of a desktop computer, a workstation computer, a computing
system comprised a cluster of processors, a networked computer, a
tablet personal computer, a laptop computer, or a personal digital
assistant, or any other suitable computing unit. In some
embodiments, any one of the one or more computing devices 1510,
1720, and/or 1540 and/or control circuitry 130 may be operable to
communicate with a database to access the first possible dataset
and/or subsequent datasets. In some embodiments, the computing
device 1510, 1720, and/or 1540 is operable to communicate with the
one or more apparatus 100 and/or 500 and/or device 200, 300, and/or
400 (e.g. control circuitry 130).
[0371] There is little distinction left between hardware and
software implementations of aspects of systems; the use of hardware
or software 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. 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;
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.
[0372] 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 may 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, etc.).
[0373] Those skilled in the art will recognize that it is common
within the art to describe devices and/or processes in the fashion
set forth herein, and thereafter use engineering practices to
integrate such described devices and/or processes into data
processing systems. That is, at least a portion of the devices
and/or processes described herein can be integrated into a data
processing system via a reasonable amount of experimentation. Those
having skill in the art will recognize that a typical data
processing system generally includes one or more of a system unit
housing, a video display device, a memory such as volatile and
non-volatile memory, processors such as microprocessors and digital
signal processors, computational entities such as operating
systems, drivers, graphical user interfaces, and applications
programs, one or more interaction devices, such as a touch pad or
screen, and/or control systems including feedback loops and control
motors (e.g., feedback for sensing position and/or velocity;
control motors for moving and/or adjusting components and/or
quantities). A typical data processing system may be implemented
utilizing any suitable commercially available components, such as
those typically found in data computing/communication and/or
network computing/communication systems.
[0374] The herein described subject matter sometimes illustrates
different components contained within, or connected with, different
other components. It is to be understood that such depicted
architectures are merely exemplary, and that in fact many other
architectures can be implemented which achieve the same
functionality.
[0375] In a conceptual sense, any arrangement of components to
achieve the same functionality is effectively "associated" such
that the desired functionality is achieved. Hence, any two
components herein combined to achieve a particular functionality
can be seen as "associated with" each other such that the desired
functionality is achieved, irrespective of architectures or
intermedial components. Likewise, any two components so associated
can also be viewed as being "operably connected", or "operably
coupled", to each other to achieve the desired functionality, and
any two components capable of being so associated can also be
viewed as being "operably couplable", to each other to achieve the
desired functionality. Specific examples of operably couplable
include but are not limited to physically mateable and/or
physically interacting components and/or wirelessly interactable
and/or wirelessly interacting components and/or logically
interacting and/or logically interactable components.
[0376] With respect to the use of substantially any plural and/or
singular terms herein, those having skill in the art can translate
from the plural to the singular and/or from the singular to the
plural as is appropriate to the context and/or application. The
various singular/plural permutations may be expressly set forth
herein for sake of clarity.
[0377] For ease of reading, all values described herein, and all
numerical ranges described herein are approximate and should be
read as including the word "about" or "approximately" prior to each
numeral, unless context indicates otherwise. For example, the range
"0.0001 to 0.01" is meant to read as "about 0.0001 to about
0.01."
[0378] 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
inventions 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 virtually any
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. For example, the phrase
"A or B" will be understood to include the possibilities of "A" or
"B" or "A and B."
[0379] All references, including but not limited to patents, patent
applications, and non-patent literature are hereby incorporated by
reference herein in their entirety.
[0380] While various aspects and embodiments have been disclosed
herein, other aspects and embodiments will be apparent to those
skilled in the art. The various aspects and embodiments disclosed
herein are for purposes of illustration and are not intended to be
limiting, with the true scope and spirit being indicated by the
following claims.
* * * * *
References