U.S. patent application number 12/931931 was filed with the patent office on 2012-02-16 for systems, devices, and methods including implantable devices with anti-microbial properties.
This patent application is currently assigned to Searete LLC, a Limited liability corporation of the State of Delaware. Invention is credited to Eleanor V. Goodall, Roderick A. Hyde, Elizabeth A. Sweeney, Lowell L. Wood, JR..
Application Number | 20120041287 12/931931 |
Document ID | / |
Family ID | 44902389 |
Filed Date | 2012-02-16 |
United States Patent
Application |
20120041287 |
Kind Code |
A1 |
Goodall; Eleanor V. ; et
al. |
February 16, 2012 |
Systems, devices, and methods including implantable devices with
anti-microbial properties
Abstract
Systems, devices, methods, and compositions are described for
providing an actively controllable implant configured to, for
example, monitor, treat, or prevent microbial growth or adherence
to the implant.
Inventors: |
Goodall; Eleanor V.;
(Seattle, WA) ; Hyde; Roderick A.; (Redmond,
WA) ; Sweeney; Elizabeth A.; (Seattle, WA) ;
Wood, JR.; Lowell L.; (Bellevue, WA) |
Assignee: |
Searete LLC, a Limited liability
corporation of the State of Delaware
|
Family ID: |
44902389 |
Appl. No.: |
12/931931 |
Filed: |
February 14, 2011 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
12931921 |
Feb 14, 2011 |
|
|
|
12931931 |
|
|
|
|
12931924 |
Feb 14, 2011 |
|
|
|
12931921 |
|
|
|
|
12931928 |
Feb 14, 2011 |
|
|
|
12931924 |
|
|
|
|
12931929 |
Feb 14, 2011 |
|
|
|
12931928 |
|
|
|
|
12931923 |
Feb 14, 2011 |
|
|
|
12931929 |
|
|
|
|
12931925 |
Feb 14, 2011 |
|
|
|
12931923 |
|
|
|
|
12931930 |
Feb 14, 2011 |
|
|
|
12931925 |
|
|
|
|
12931920 |
Feb 14, 2011 |
|
|
|
12931930 |
|
|
|
|
12931926 |
Feb 14, 2011 |
|
|
|
12931920 |
|
|
|
|
12931927 |
Feb 14, 2011 |
|
|
|
12931926 |
|
|
|
|
12931922 |
Feb 14, 2011 |
|
|
|
12931927 |
|
|
|
|
12315880 |
Dec 4, 2008 |
|
|
|
12931922 |
|
|
|
|
12315881 |
Dec 4, 2008 |
|
|
|
12315880 |
|
|
|
|
12315882 |
Dec 4, 2008 |
|
|
|
12315881 |
|
|
|
|
12315883 |
Dec 4, 2008 |
|
|
|
12315882 |
|
|
|
|
12315884 |
Dec 4, 2008 |
|
|
|
12315883 |
|
|
|
|
12315885 |
Dec 4, 2008 |
|
|
|
12315884 |
|
|
|
|
12380553 |
Feb 27, 2009 |
|
|
|
12315885 |
|
|
|
|
12592976 |
Dec 3, 2009 |
|
|
|
12380553 |
|
|
|
|
12660156 |
Feb 19, 2010 |
|
|
|
12592976 |
|
|
|
|
12800766 |
May 21, 2010 |
|
|
|
12660156 |
|
|
|
|
12800774 |
May 21, 2010 |
|
|
|
12800766 |
|
|
|
|
12800778 |
May 21, 2010 |
|
|
|
12800774 |
|
|
|
|
12800779 |
May 21, 2010 |
|
|
|
12800778 |
|
|
|
|
12800780 |
May 21, 2010 |
|
|
|
12800779 |
|
|
|
|
12800781 |
May 21, 2010 |
|
|
|
12800780 |
|
|
|
|
12800786 |
May 21, 2010 |
|
|
|
12800781 |
|
|
|
|
12800790 |
May 21, 2010 |
|
|
|
12800786 |
|
|
|
|
12800791 |
May 21, 2010 |
|
|
|
12800790 |
|
|
|
|
12800792 |
May 21, 2010 |
|
|
|
12800791 |
|
|
|
|
12800793 |
May 21, 2010 |
|
|
|
12800792 |
|
|
|
|
12800798 |
May 21, 2010 |
|
|
|
12800793 |
|
|
|
|
12927297 |
Nov 10, 2010 |
|
|
|
12800798 |
|
|
|
|
12927284 |
Nov 10, 2010 |
|
|
|
12927297 |
|
|
|
|
12927288 |
Nov 10, 2010 |
|
|
|
12927284 |
|
|
|
|
12927296 |
Nov 10, 2010 |
|
|
|
12927288 |
|
|
|
|
12927287 |
Nov 10, 2010 |
|
|
|
12927296 |
|
|
|
|
12927294 |
Nov 10, 2010 |
|
|
|
12927287 |
|
|
|
|
12927285 |
Nov 10, 2010 |
|
|
|
12927294 |
|
|
|
|
12927290 |
Nov 10, 2010 |
|
|
|
12927285 |
|
|
|
|
12927291 |
Nov 10, 2010 |
|
|
|
12927290 |
|
|
|
|
12927295 |
Nov 10, 2010 |
|
|
|
12927291 |
|
|
|
|
Current U.S.
Class: |
600/309 |
Current CPC
Class: |
A61L 29/00 20130101;
A61L 2/24 20130101; A61L 31/026 20130101; A61L 31/16 20130101; A61M
25/0045 20130101; B82Y 30/00 20130101; A61L 2/232 20130101; A61L
17/145 20130101; A61L 29/16 20130101; A61L 2300/606 20130101; A61M
27/006 20130101; A61L 2/08 20130101; A61L 27/54 20130101; B82Y 5/00
20130101; A61L 2/26 20130101; A61L 2202/14 20130101; A61L 2300/108
20130101; B82Y 40/00 20130101; A61L 31/08 20130101; A61L 27/306
20130101; A61L 2300/404 20130101; A61L 2/14 20130101; A61L 31/024
20130101; A61L 31/14 20130101; A61L 27/28 20130101; A61L 29/08
20130101; A61L 2/0011 20130101; A61L 2300/10 20130101 |
Class at
Publication: |
600/309 |
International
Class: |
A61B 5/00 20060101
A61B005/00 |
Claims
1. A insertable device, comprising: a body structure having an
outer surface and an inner surface defining one or more fluid-flow
passageways; one or more anti-microbial regions of the body
structure including at least one selectively actuatable
anti-microbial agent reservoir, the reservoir configured to be
actuated by the presence of at least one microorganism, and
configured to actively deliver one or more anti-microbial agents to
the one or more anti-microbial regions of the body structure.
2. The insertable device of claim 1, further comprising at least
one sensor operably coupled to at least one selectively actuatable
anti-microbial agent reservoir.
3. The insertable device of claim 2, wherein the at least one
sensor is configured to detect the presence of at least one
microorganism in at least one of the anti-microbial regions within
at least one of the one or more fluid-flow passageways.
4. The insertable device of claim 1, wherein the anti-microbial
regions form a spatial or temporal pattern extending over at least
a portion of the body structure.
5. The insertable device of claim 1, further comprising at least
one sensor configured for detecting the presence of at least one
microorganism.
6. The insertable device of claim 5, further comprising a
controller operably coupled to the at least one sensor, the
controller configured to actuate at least one of the anti-microbial
regions in response to detected information from the at least one
sensor.
7. The insertable device of claim 5, further comprising a
controller operably coupled to the at least one sensor, the
controller configured to actuate at least one of the plurality of
the anti-microbial regions in response to at least one of a
scheduled program, external command, history of a previous presence
of a microorganism, or history of a previous activation.
8. The insertable device of claim 5, further comprising activating
means for concurrently or sequentially activating two or more of
the anti-microbial regions determined to have at least one
microorganism present.
9. The insertable device of claim 8, wherein the activating means
includes one or more switching elements.
10. The insertable device of claim 8, wherein the activating means
includes at least one of an electro-mechanical switch,
electrochemical switch, optical switch, electrical switch, magnetic
switch, electro-optical switch, or acousto-optical switch.
11. The insertable device of claim 5, wherein the sensor includes
at least one identification code.
12. The insertable device of claim 11, wherein the at least one
sensor is configured to implement instructions according to the at
least one identification code.
13. The insertable device of claim 5, wherein the sensor is
operably coupled to a microorganism biomarker array.
14.-16. (canceled)
17. The insertable device of claim 5, wherein the sensor includes
one or more functionalized cantilevers.
18. The insertable device of claim 5, wherein the sensor includes a
microbial component capture layer.
19. The insertable device of claim 18, wherein the microbial
component capture layer includes an array of different binding
molecules that specifically bind one or more components of at least
one microorganism.
20. The insertable device of claim 5, further comprising at least
one computing device.
21. The insertable device of claim 20, further comprising one or
more instructions that when executed on the at least one computing
device cause the at least one computing device to generate at least
one output to a user.
22. The insertable device of claim 21, wherein the at least one
output includes at least one of a treatment protocol,
identification of a detected microorganism, status of the
insertable device, or location of a detected microorganism.
23. The insertable device of claim 21, wherein the user includes at
least one entity.
24. The insertable device of claim 23, wherein the at least one
entity includes at least one person or computer.
25. The insertable device of claim 21, wherein the at least one
output is in real-time.
26. The insertable device of claim 21, wherein the at least one
output is associated with historical information.
27. The insertable device of claim 21, wherein the at least one
output includes output to a user readable display.
28. The insertable device of claim 27, wherein the user readable
display is operably coupled to the insertable device.
29. The insertable device of claim 27, wherein the user readable
display includes a human readable display.
30. The insertable device of claim 27, wherein the user readable
display includes one or more active displays.
31. The insertable device of claim 27, wherein the user readable
display includes one or more passive displays.
32. The insertable device of claim 27, wherein the user readable
display includes one or more of a numeric format, graphical format,
or audio format.
33. The insertable device of claim 1, wherein the anti-microbial
agent includes at least one of an anti-fungal agent, anti-parasitic
agent, bacteriophage or antibiotic.
34. The insertable device of claim 33, wherein the bacteriophage
includes an engineered enzymatically active bacteriophage.
35. The insertable device of claim 33, wherein the anti-microbial
agent includes at least two different bacteriophage sets.
36.-47. (canceled)
48. The insertable device of claim 1, wherein the body structure
further includes at least one porous material.
49. The insertable device of claim 1, wherein at least one of the
plurality of anti-microbial regions includes at least one porous
material.
50. The insertable device of claim 49, wherein the at least one
porous material is configured to capture at least one microorganism
proximate to at least one of the inner surface or the outer surface
of the body structure.
51. The insertable device of claim 50, wherein the at least one
porous material is further configured to retain the captured
microorganism.
52. The insertable device of claim 50, wherein the porous material
includes hydrophobic polycations bound thereto.
53. The insertable device of claim 52, wherein the hydrophobic
polycations are covalently bound to the porous material.
54.-55. (canceled)
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is related to and claims the benefit
of the earliest available effective filing dates from the following
listed applications (the "Related Applications") (e.g., claims
earliest available priority dates for other than provisional patent
applications or claims benefits under 35 U.S.C. .sctn.116(e) for
provisional patent applications, for any and all parent,
grandparent, great-grandparent, etc. applications of the Related
Applications). All subject matter of the Related Applications and
of any and all parent, grandparent, great-grandparent, etc.
applications of the Related Applications is incorporated herein by
reference to the extent such subject matter is not inconsistent
herewith.
RELATED APPLICATIONS
[0002] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming ELEANOR V. GOODALL, RODERICK A. HYDE, ELIZABETH
A. SWEENEY, LOWELL L. WOOD, JR. as inventors, filed 14 Feb. 2011,
having Docket No. 0307-004-032-CIP001.
[0003] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming ELEANOR V. GOODALL, RODERICK A. HYDE, ELIZABETH
A. SWEENEY, LOWELL L. WOOD, JR. as inventors, filed 14 Feb. 2011,
having Docket No. 0307-004-032A-CIP001.
[0004] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming ELEANOR V. GOODALL, RODERICK A. HYDE, ELIZABETH
A. SWEENEY, LOWELL L. WOOD, JR. as inventors, filed 14 Feb. 2011,
having Docket No. 0307-004-032B-CIP001.
[0005] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming ELEANOR V. GOODALL, RODERICK A. HYDE, ELIZABETH
A. SWEENEY, LOWELL L. WOOD, JR. as inventors, filed 14 Feb. 2011,
having Docket No. 0307-004-032C-CIP001.
[0006] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming ELEANOR V. GOODALL, RODERICK A. HYDE, ELIZABETH
A. SWEENEY, LOWELL L. WOOD, JR. as inventors, filed 14 Feb. 2011,
having Docket No. 0307-004-032D-CIP001.
[0007] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming ELEANOR V. GOODALL, RODERICK A. HYDE, ELIZABETH
A. SWEENEY, LOWELL L. WOOD, JR. as inventors, filed 14 Feb. 2011,
having Docket No. 0307-004-032E-CIP001.
[0008] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming ELEANOR V. GOODALL, RODERICK A. HYDE, ELIZABETH
A. SWEENEY, LOWELL L. WOOD, JR. as inventors, filed 14 Feb. 2011,
having Docket No. 0307-004-032G-CIP001.
[0009] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming EDWARD S. BOYDEN, ROY P. DIAZ, RODERICK A. HYDE,
JORDIN T. KARE, ELIZABETH A. SWEENEY, LOWELL L. WOOD, JR. as
inventors, filed 14 Feb. 2011, having Docket No.
0307-004-032-CIP002.
[0010] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming EDWARD S. BOYDEN, ROY P. DIAZ, RODERICK A. HYDE,
JORDIN T. KARE, ELIZABETH A. SWEENEY, LOWELL L. WOOD, JR. as
inventors, filed 14 Feb. 2011, having Docket No.
0307-004-032A-CIP002.
[0011] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled. SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming EDWARD S. BOYDEN, ROY P. DIAZ, RODERICK A. HYDE,
JORDIN T. KARE, ELIZABETH A. SWEENEY, LOWELL L. WOOD, JR. as
inventors, filed 14 Feb. 2011, having Docket No.
0307-004-032B-CIP002.
[0012] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. To be Assigned, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING IMPLANTABLE DEVICES WITH ANTI-MICROBIAL
PROPERTIES, naming EDWARD S. BOYDEN, ROY P. DIAZ, RODERICK A. HYDE,
JORDIN T. KARE, ELIZABETH A. SWEENEY, LOWELL L. WOOD, JR. as
inventors, filed 14 Feb. 2011, having Docket No.
0307-004-032C-CIP002.
[0013] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/315,880, titled SYSTEM, DEVICES, AND
METHODS INCLUDING ACTIVELY-CONTROLLABLE SUPEROXIDE WATER GENERATING
SYSTEMS, naming EDWARD S. BOYDEN, RALPH G. DACEY, JR., GREGORY J.
DELLA ROCCA, JOSHUA L. DOWLING, RODERICK A. HYDE, MURIEL Y.
ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD,
DENNIS J. RIVET, PAUL SANTIAGO, MICHAEL A. SMITH, TODD J. STEWART,
ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L. WOOD, JR.,
VICTORIA Y. H. WOOD as inventors, filed 4 Dec. 2008, which is
currently co-pending, or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0014] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/315,881, titled SYSTEM, DEVICES, AND
METHODS INCLUDING STERILIZING EXCITATION DELIVERY IMPLANTS WITH
CRYPTOGRAPHIC LOGIC COMPONENTS, naming EDWARD S. BOYDEN, RALPH G.
DACEY, JR., GREGORY J. DELLA ROCCA, JOSHUA L. DOWLING, RODERICK A.
HYDE, MURIEL Y. ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN
P. MYHRVOLD, DENNIS J. RIVET, PAUL SANTIAGO, MICHAEL A. SMITH, TODD
J. STEWART, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L.
WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 4 Dec. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0015] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/315,882, titled SYSTEM, DEVICES, AND
METHODS INCLUDING STERILIZING EXCITATION DELIVERY IMPLANTS WITH
GENERAL CONTROLLERS AND ONBOARD POWER, naming EDWARD S. BOYDEN,
RALPH G. DACEY, JR., GREGORY J. DELLA ROCCA, JOSHUA L. DOWLING,
RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN T. KARE, ERIC C.
LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET, PAUL SANTIAGO,
MICHAEL A. SMITH, TODD J. STEWART, ELIZABETH A. SWEENEY, CLARENCE
T. TEGREENE, LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors,
filed 4 Dec. 2008, which is currently co-pending, or is an
application of which a currently co-pending application is entitled
to the benefit of the filing date.
[0016] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/315,883, titled SYSTEM, DEVICES, AND
METHODS INCLUDING STERILIZING EXCITATION DELIVERY IMPLANTS WITH
GENERAL CONTROLLERS AND ONBOARD POWER, naming EDWARD S. BOYDEN,
RALPH G. DACEY, JR., GREGORY J. DELLA ROCCA, JOSHUA L. DOWLING,
RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN T. KARE, ERIC C.
LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET, PAUL SANTIAGO,
MICHAEL A. SMITH, TODD J. STEWART, ELIZABETH A. SWEENEY, CLARENCE
T. TEGREENE, LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors,
filed 4 Dec. 2008, which is currently co-pending, or is an
application of which a currently co-pending application is entitled
to the benefit of the filing date.
[0017] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/315,884, titled SYSTEM, DEVICES, AND
METHODS INCLUDING ACTIVELY CONTROLLABLE STERILIZING EXCITATION
DELIVERY IMPLANTS, naming EDWARD S. BOYDEN, RALPH G. DACEY, JR.,
GREGORY J. DELLA ROCCA, JOSHUA L. DOWLING, RODERICK A. HYDE, MURIEL
Y. ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD,
DENNIS J. RIVET, PAUL SANTIAGO, MICHAEL A. SMITH, TODD J. STEWART,
ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L. WOOD, JR.,
VICTORIA Y. H. WOOD as inventors, filed 4 Dec. 2008, which is
currently co-pending, or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0018] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/315,885, titled CONTROLLABLE ELECTROSTATIC
AND ELECTROMAGNETIC STERILIZING EXCITATION DELIVERY SYSTEMS,
DEVICE, AND METHODS, naming EDWARD S. BOYDEN, RALPH G. DACEY, JR.,
GREGORY J. DELLA ROCCA, JOSHUA L. DOWLING, RODERICK A. HYDE, MURIEL
Y. ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD,
DENNIS J. RIVET, PAUL SANTIAGO, MICHAEL A. SMITH, TODD J. STEWART,
ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L. WOOD, JR.,
VICTORIA Y. H. WOOD as inventors, filed 4 Dec. 2008, which is
currently co-pending, or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0019] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/380,553, titled SYSTEM, DEVICES, AND
METHODS INCLUDING ACTIVELY CONTROLLABLE STERILIZING EXCITATION
DELIVERY IMPLANTS, naming EDWARD S. BOYDEN, RALPH G. DACEY, JR.,
GREGORY J. DELLA ROCCA, JOSHUA L. DOWLING, RODERICK A. HYDE, MURIEL
Y. ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD,
DENNIS J. RIVET, PAUL SANTIAGO, MICHAEL A. SMITH, TODD J. STEWART,
ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L. WOOD, JR.,
VICTORIA Y. H. WOOD as inventors, filed 27 Feb. 2009, which is
currently co-pending, or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0020] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/592,976, titled SYSTEM, DEVICES, AND
METHODS INCLUDING ACTIVELY-CONTROLLABLE STERILIZING EXCITATION
DELIVERY IMPLANTS, naming EDWARD S. BOYDEN, RALPH G. DACEY, JR.,
GREGORY J. DELLA ROCCA, JOSHUA L. DOWLING, RODERICK A. HYDE, MURIEL
Y. ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD,
DENNIS J. RIVET, PAUL SANTIAGO, MICHAEL A. SMITH, TODD J. STEWART,
ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L. WOOD, JR.,
VICTORIA Y. H. WOOD as inventors, filed 3 Dec. 2009, which is
currently co-pending or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0021] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/660,156, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 19
Feb. 2010, which is currently co-pending or is an application of
which a currently co-pending application is entitled to the benefit
of the filing date.
[0022] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,766, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0023] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,774, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0024] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,778, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0025] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,779, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0026] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,780, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0027] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,781, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0028] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,786, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0029] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,790, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0030] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,791, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0031] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,792, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0032] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,793, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0033] For purposes of the United States Patent and Trademark
Office (USPTO) extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/800,798, titled SYSTEMS, DEVICES, AND
METHODS INCLUDING INFECTION-FIGHTING AND MONITORING SHUNTS, naming
RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN
T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 21 May
2010, which is currently co-pending or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0034] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,297, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS HAVING COMPONENTS THAT ARE ACTIVELY CONTROLLABLE BETWEEN
TRANSMISSIVE AND REFLECTIVE STATES, naming RALPH G. DACEY, JR.,
RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN T. KARE, ERIC C.
LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET, MICHAEL A. SMITH,
ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L. WOOD, JR.,
VICTORIA Y. H. WOOD as inventors, filed 10 Nov. 2010, which is
currently co-pending or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0035] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,284, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS HAVING COMPONENTS THAT ARE ACTIVELY CONTROLLABLE BETWEEN
TWO OR MORE WETTABILITY STATES, naming RALPH G. DACEY, JR.,
RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN T. KARE, ERIC C.
LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET, MICHAEL A. SMITH,
ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L. WOOD, JR.,
VICTORIA Y. H. WOOD as inventors, filed 10 Nov. 2010, which is
currently co-pending or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0036] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,288, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS HAVING AN ACTIVELY CONTROLLABLE THERAPEUTIC AGENT
DELIVERY COMPONENT, naming RALPH G. DACEY, JR., RODERICK A. HYDE,
MURIEL Y. ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P.
MYHRVOLD, DENNIS J. RIVET, MICHAEL A. SMITH, ELIZABETH A. SWEENEY,
CLARENCE T. TEGREENE, LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as
inventors, filed 10 Nov. 2010, which is currently co-pending or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date.
[0037] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,296, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS HAVING UV-ENERGY EMITTING COATINGS, naming RALPH G.
DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN T. KARE,
ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET, MICHAEL A.
SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L. WOOD,
JR., VICTORIA Y. H. WOOD as inventors, filed 10 Nov. 2010, which is
currently co-pending or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0038] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,287, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS HAVING SELF-CLEANING SURFACES, naming RALPH G. DACEY,
JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN T. KARE, ERIC C.
LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET, MICHAEL A. SMITH,
ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE, LOWELL L. WOOD, JR.,
VICTORIA Y. H. WOOD as inventors, filed 10 Nov. 2010, 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.
[0039] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,294, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS CONFIGURED TO MONITOR BIOFILM FORMATION HAVING BIOFILM
SPECTRAL INFORMATION CONFIGURED AS A DATA STRUCTURE, naming RALPH
G. DACEY, JR., RODERICK A. HYDE, MURIEL Y. ISHIKAWA, JORDIN T.
KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD, DENNIS J. RIVET,
MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE T. TEGREENE,
LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors, filed 10
Nov. 2010, 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.
[0040] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,285, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS HAVING ACOUSTICALLY ACTUATABLE WAVEGUIDE COMPONENTS FOR
DELIVERING A STERILIZING STIMULUS TO A REGION PROXIMATE A SURFACE
OF THE CATHETER, naming RALPH G. DACEY, JR., RODERICK A. HYDE,
MURIEL Y. ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P.
MYHRVOLD, DENNIS J. RIVET, MICHAEL A. SMITH, ELIZABETH A. SWEENEY,
CLARENCE T. TEGREENE, LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as
inventors, filed 10 Nov. 2010, 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.
[0041] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,290, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS HAVING LIGHT REMOVABLE COATINGS BASED ON A SENSED
CONDITION, naming RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y.
ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD,
DENNIS J. RIVET, MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE
T. TEGREENE, LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors,
filed 10 Nov. 2010, 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.
[0042] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,291, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS HAVING LIGHT REMOVABLE COATINGS BASED ON A SENSED
CONDITION, naming RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y.
ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD,
DENNIS J. RIVET, MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE
T. TEGREENE, LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors,
filed 10 Nov. 2010, 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.
[0043] For purposes of the USPTO extra-statutory requirements, the
present application is related to U.S. patent application Ser. No.
12/927,295, titled SYSTEMS, DEVICES, AND METHODS INCLUDING
CATHETERS CONFIGURED TO RELEASE ULTRAVIOLET ENERGY ABSORBING
AGENTS, naming RALPH G. DACEY, JR., RODERICK A. HYDE, MURIEL Y.
ISHIKAWA, JORDIN T. KARE, ERIC C. LEUTHARDT, NATHAN P. MYHRVOLD,
DENNIS J. RIVET, MICHAEL A. SMITH, ELIZABETH A. SWEENEY, CLARENCE
T. TEGREENE, LOWELL L. WOOD, JR., VICTORIA Y. H. WOOD as inventors,
filed 10 Nov. 2010, 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.
[0044] The United States Patent Office (USPTO) has published a
notice to the effect that the USPTO's computer programs require
that patent applicants reference both a serial number and indicate
whether an application is a continuation, continuation-in-part, or
divisional of a parent application. Stephen G. Kunin, Benefit of
Prior-Filed Application, USPTO Official Gazette Mar. 18, 2003. 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 has provided designation(s) of a
relationship between the present application and its parent
application(s) as set forth above, but expressly points out that
such designation(s) are not to be construed in any way as any type
of commentary and/or admission as to whether or not the present
application contains any new matter in addition to the matter of
its parent application(s).
SUMMARY
[0045] The present disclosure is directed to, among other things, a
insertable device. In an embodiment, the insertable device includes
a body structure having an outer surface and an inner surface
defining one or more fluid-flow passageways. In an embodiment,
systems and methods of operating the insertable device are
included.
[0046] In an embodiment, the insertable device includes a plurality
of anti-microbial regions arranged in at least one of a spatial
pattern or temporal pattern, the plurality of anti-microbial
regions included on at least one of the outer surface or the inner
surface, or embedded in the body structure.
[0047] In an embodiment, the a body structure defines one or more
fluid-flow passageways; the body structure including one or more
selectively actuatable anti-microbial regions including at least
one anti-microbial agent, the one or more selectively actuatable
anti-microbial regions configured to direct at least one
anti-microbial agent to one or more areas of at least one of the
outer surface of the body structure, the inner surface of the body
structure, or embedded in the internal body structure; and one or
more sensors configured to detect at least one microbial component
proximate one or more areas of the body structure.
[0048] In an embodiment, the insertable device includes a body
structure having an outer surface and an inner surface defining one
or more fluid-flow passageways, the body structure having a
plurality of actuatable anti-microbial regions that are selectively
actuatable between at least a first actuatable state and a second
actuatable state; one or more sensors configured to detect at least
one microbial component in a biological sample proximate at least
one of the outer surface or the inner surface of the body
structure.
[0049] In an embodiment, the insertable device includes a body
structure having an outer surface and an inner surface defining one
or more fluid-flow passageways; at least one anti-microbial region
configured to deliver at least one anti-microbial agent to one or
more areas of at least one of the outer surface, the inner surface,
or embedded in the internal body structure; a sensor configured to
detect at least one microbial component proximate at least one of
the outer surface or the inner surface of the body structure; and
one or more computer-readable memory media having microbial marker
information configured as a data structure, the data structure
including a characteristic information section having
characteristic microbial information representative of the presence
of at least one microorganism proximate at least one of the outer
surface or the inner surface of the body structure, or the interior
of the fluid-flow passageway.
[0050] In an embodiment, the insertable device includes a body
structure having an outer surface and an inner surface defining one
or more fluid-flow passageways; one or more anti-microbial regions
including at least one D-amino acid coating on at least one of the
outer surface, inner surface, or embedded in the body
structure.
[0051] In an embodiment, the insertable device includes a body
structure having an outer surface and an inner surface defining one
or more fluid-flow passageways; one or more anti-microbial regions
including at least one anti-microbial coating actuatable by the
presence of at least one microorganism, and configured to actively
elute at least one anti-microbial agent proximate to at least one
of the outer surface, or inner surface of the body structure.
[0052] In an embodiment, the insertable device includes a body
structure having an outer surface and an inner surface defining one
or more fluid-flow passageways; one or more anti-microbial regions
of the body structure including at least one anti-microbial agent
reservoir, the reservoir configured to release one or more
anti-microbial agents to the one or more anti-microbial regions of
the body structure.
[0053] In an embodiment, the insertable device includes a body
structure having an outer surface and an inner surface defining one
or more fluid-flow passageways; one or more anti-microbial regions
of the body structure including at least one selectively actuatable
anti-microbial agent reservoir, the reservoir configured to be
actuated by the presence of at least one microorganism, and
configured to actively deliver one or more anti-microbial agents to
the one or more anti-microbial regions of the body structure.
[0054] In an embodiment, the insertable device includes a body
structure having an outer surface and an inner surface defining one
or more fluid-flow passageways; and one or more actuatable
anti-microbial regions configured to direct at least one
anti-microbial agent to one or more regions proximate at least one
of the outer surface or inner surface of the body structure.
[0055] 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
[0056] FIG. 1A illustrates a particular embodiment of a device
disclosed herein.
[0057] FIG. 1B illustrates a close up view of a component of the
device illustrated in FIG. 1A.
[0058] FIG. 2A illustrates a particular embodiment of a device
disclosed herein.
[0059] FIG. 2B illustrates a close up of the device illustrated in
FIG. 2A.
[0060] FIG. 3 illustrates a particular embodiment of a device in an
embodiment of a system disclosed herein.
[0061] FIG. 4A illustrates a close up of a particular embodiment of
a component of a device disclosed herein.
[0062] FIG. 4B illustrates a close up of a particular embodiment of
a component of a device disclosed herein.
[0063] FIG. 5A illustrates a close up of a particular embodiment of
a component of a device disclosed herein.
[0064] FIG. 5B illustrates a close up of a particular embodiment of
a component of a device disclosed herein.
[0065] FIG. 6 illustrates a particular embodiment of a component of
a device disclosed herein.
[0066] FIG. 7 illustrates a particular embodiment of a device in an
embodiment of a system disclosed herein.
[0067] FIG. 8 illustrates a particular embodiment of a device in an
embodiment of a system disclosed herein.
[0068] FIG. 9 illustrates a partial view of an embodiment of a
method disclosed herein.
[0069] FIG. 10 illustrates a partial view of an embodiment of a
method disclosed herein.
[0070] FIG. 11 illustrates a partial view of an embodiment of a
method disclosed herein.
[0071] FIG. 12 illustrates a partial view of an embodiment of a
method disclosed herein.
[0072] FIG. 13 illustrates a partial view of an embodiment of a
method disclosed herein.
[0073] FIG. 14 illustrates a partial view of an embodiment of a
method disclosed herein.
[0074] FIG. 15 illustrates a partial view of an embodiment of a
method disclosed herein.
[0075] FIG. 16 illustrates a partial view of an embodiment of a
method disclosed herein.
[0076] FIG. 17 illustrates a partial view of an embodiment of a
method disclosed herein.
[0077] FIG. 18 illustrates a partial view of an embodiment of a
method disclosed herein.
[0078] FIG. 19 illustrates a partial view of an embodiment of a
method disclosed herein.
[0079] FIG. 20 illustrates a partial view of an embodiment of a
method disclosed herein.
[0080] FIG. 21 illustrates a partial view of an embodiment of a
method disclosed herein.
[0081] FIG. 22 illustrates a partial view of an embodiment of a
method disclosed herein.
[0082] FIG. 23 illustrates a partial view of an embodiment of a
method disclosed herein.
[0083] FIG. 24 illustrates a partial view of an embodiment of a
method disclosed herein.
[0084] FIG. 25 illustrates a partial view of an embodiment of a
method disclosed herein.
[0085] FIG. 26 illustrates a partial view of an embodiment of a
method disclosed herein.
[0086] FIG. 27 illustrates a partial view of an embodiment of a
method disclosed herein.
[0087] FIG. 28 illustrates a partial view of an embodiment of a
method disclosed herein.
[0088] FIG. 29 illustrates a partial view of an embodiment of a
method disclosed herein.
[0089] FIG. 30 illustrates a partial view of an embodiment of a
method disclosed herein.
DETAILED DESCRIPTION
[0090] In the following detailed description, reference is made to
the accompanying drawings, which form a part hereof. In the
drawings, similar symbols typically identify similar components,
unless context dictates otherwise. The illustrative embodiments
described in the detailed description, drawings, and claims are not
meant to be limiting. Other embodiments can be utilized, and other
changes can be made, without departing from the spirit or scope of
the subject matter presented here.
[0091] Insertable devices, such as implantable shunts (e.g.,
cardiac shunts, cerebral shunts, portacaval shunts, portosystemic
shunts, pulmonary shunts, or the like), catheters (e.g., central
venous catheters, multi-lumen catheters, peripherally inserted
central catheters, Quinton catheters, Swan-Ganz catheters, tunneled
catheters, or the like), or medical ports (e.g., arterial ports,
low profile ports, multi-lumen ports, vascular ports, or the like)
are useful for, among other things, managing movement of fluids;
directly detecting (e.g., assessing, calculating, evaluating,
determining, gauging, identifying, measuring, monitoring,
quantifying, resolving, sensing, or the like) mechanical, physical,
or biochemical information (e.g., the presence of a biomarker,
intracranial pressure, blood pressure, a disease state, or the
like) associated with a biological subject; draining or collecting
body fluids; as well as for administering therapeutics,
medications, pharmaceuticals, intravenous fluids, blood products,
or delivering parenteral nutrition.
[0092] Infections, malfunctions (e.g., blocked or clogged
fluid-flow passageways), and failures account for many of the
complications associated with catheter devices and pose tremendous
consequences for patients. For example, during an infection, an
infectious agent (e.g., fungi, micro-organisms, parasites,
pathogens (e.g., viral pathogens, bacterial pathogens, or the
like), prions, viroids, viruses, or the like) generally interferes
with the normal functioning of a biological subject, and causes, in
some cases, chronic wounds, gangrene, loss of an infected tissue,
loss of an infected limb, and occasionally death of the biological
subject. Infections associated with catheter devices account for a
significant number of nosocomial infections. Despite sterilization
and aseptic procedures, infection remains a major impediment to
medical implants and catheter devices, including artificial hearts
or heart valves, subcutaneous sensors, contact lens, artificial
joints, artificial prosthetics, breast implants, cochlear implants,
dental implants, neural implants, orthopedic implants, ocular
implants, prostheses, implantable electronic devices, implantable
medical devices, catheters, contact lens, implantable biological
fluid drainage system, mechanical heart valves, stents,
subcutaneous sensors, shunts, vertebral spacers, and the like.
Implant associated (including catheter device-associated)
infections are often difficult to detect, problematic to cure, and
expensive to manage. For example, in cases where the infection does
not quickly subside, it sometimes becomes necessary to remove the
catheter device. Implant device-associated infections can result
from microorganism (e.g., bacteria) adhesion and possibly
subsequent biofilm formation proximate an implantation site. For
example, biofilm-forming microorganisms sometimes colonize catheter
devices at least partially implanted into a biological subject.
Once a biofilm-induced infection takes hold, it can prove difficult
to treat, and can even be fatal for the biological subject.
[0093] The present disclosure includes, but is not limited to,
systems, devices, and methods, of a catheter device configured to,
for example, detect (e.g., assess, calculate, evaluate, determine,
gauge, identify, measure, monitor, quantify, resolve, sense, or the
like) an infectious agent (e.g., microorganism) present in, for
example, a biological fluid. A non-limiting example includes
systems, devices, and methods including a catheter device
configured to, for example, detect an infectious agent present in,
for example, a tissue proximate a catheter device that is at least
partially implanted into a biological subject.
[0094] An aspect includes systems, devices, methods, and
compositions for actively or passively detecting, treating, or
preventing an infection, a fluid vessel abnormality (e.g., an
obstruction), a biological fluid abnormality (e.g., cerebrospinal
fluid abnormality, hematological abnormality, components
concentration or level abnormality, flow abnormality, or the like),
or the like. A non-limiting example includes systems, devices, and
methods for actively detecting, treating, or preventing an
infection or presence of at least one microorganism associated with
a shunt or other catheter device. An aspect includes systems,
devices, and methods for managing movement of fluids; directly
detecting and monitoring functions or conditions (e.g., mechanical,
physical, physiological, or biochemical functions or conditions)
associated with a biological subject; draining or collecting body
fluids; providing access to an interior of a biological subject;
distending at least one passageway; as well as for administering
therapeutics, medications, pharmaceuticals, intravenous fluids, or
parenteral nutrition. A non-limiting example includes systems,
devices, and methods for actively detecting, treating, or
preventing fluid-flow obstructions in shunts or other catheter
devices.
[0095] In certain aspects, at least one of the inner surface or the
outer surface of the body structure of a catheter device disclosed
herein includes at least one surface with reversibly switchable or
actuatable properties. For example, in an embodiment, the surface
includes a nanolayer or microlayer of a material that switches from
a first conformation (i.e. a first anti-microbial state) to a
second conformation (i.e. a second anti-microbial state) as a
result of surface chemistry or charge (which can be triggered by
the presence of a microorganism or other pathogen, for example). In
another example, the surface material is actuatable when an
external stimulus is applied (e.g., electrical, electrochemical,
magnetic, optical, electro-optical, etc.). See, for example, U.S.
Patent App. Pub. No. 2006/0263033, which is incorporated herein by
reference. In an embodiment, the presence of at least one
microorganism acts as the external stimulus. In an embodiment, the
external stimulus includes at least one of a chemical, electrical,
or electro-chemical property. In an embodiment, the external
stimulus includes at least one temporal gradient, spatial gradient,
or concentration gradient.
[0096] For example, wettability of a surface can be switched or
actuated. The wettability of a substrate can be determined using
various technologies and methodologies including contact angle
methods, the Goniometer method, the Whilemy method, or the Sessile
drop technique. Wetting is a process by which a liquid interacts
with a solid. Wettability (the degree of wetting) is determined by
a force balance between adhesive and cohesive force and is often
characterized by a contact angle. The contact angle is the angle
made by the intersection of the liquid/solid interface and the
liquid/air interface. Alternatively, it is the angle between a
solid sample's surface and the tangent of a droplet's ovate shape
at the edge of the droplet. Contact angle measurements provide a
measure of interfacial energies and conveys direct information
regarding hydrophilicity or hydrophobicity of a surface. For
example, superhydrophilic surfaces have contact angles less than
about 5 degrees, hydrophilic surfaces have contact angles less than
about 90 degrees, hydrophobic surfaces have contact angles greater
than about 90 degrees, and superhydrophobic surfaces have contact
angles greater than about 150 degrees.
[0097] In an embodiment, the anti-microbial region includes at
least one nanotube forest of vertically aligned carbon nanotubes.
See, for example, Gjerde, et al., Nanotech. Vol. 17, pp. 4917-4922
(2006), which is incorporated herein by reference. For example, the
nanotube forest, due to its roughness, not only exhibits very low
static friction and dynamic friction, but it also acts as a springy
and mechanically compliant surface, making it possible to lift up
and manipulate delicate nanostructures such as organic nanofibers.
Id.
[0098] In an embodiment, the surface of at least one of the inner
surface or outer surface of the body structure includes a
capillarity-based switchable surface, which includes a surface
tension force from several small liquid bridges, whose contacts are
quickly made or broken with electronic controls, thus switching the
surface. See, for example, Vogel and Steen, PNAS Early Edition on
the web at pnas.org/cgi/doi/10.1073/pnas.0914720107), the content
of which is incorporated herein by reference.
[0099] In an embodiment, at least one of the inner surface or outer
surface of the body structure includes a wettablity switchable
surface, including, for example a metal/polymer membrane with
hydrophobic microposts. See Chen, et al. J. Micromech. Microeng.
Vol. 17, pp. 489-495 (2007), which is incorporated herein by
reference. For example, the water contact angles can be manipulated
from 131 degrees to 152 degrees, depending on the fraction of a
liquid/solid interface. Id. The process of surface wetting induced
by morphology change (SWIM) allows a change in total surface area
that contacts a water droplet, based on the number of microposts
that are articulated at any given time, this allows for the change
in wettability state. Id.
[0100] In an embodiment, the anti-microbial region includes at
least one patterned surface configured to resist or enhance
bioadhesion of microbes compared to the base surface. In an
embodiment, the at least one anti-microbial region includes a
surface with reversibly switchable properties (e.g., the surface
switches from a first conformation state to a second conformation
state when an external stimulus is applied). See, for example, U.S.
Patent App. Pub. No. 2006/0263033, which is incorporated herein by
reference.
[0101] In an embodiment, at least one sensor is operably coupled to
the surface and is configured to detect at least one microbial
component. For example, in particular instances the surface
properties are switchable or actuatable between or among at least
one of hydrophilicity, hydrophobicity, electrical charge, chemical
composition, polarizability, transparence, conductivity, light
absorption, osmotic potential, zeta potential, surface energy,
coefficient of friction, or tackiness.
[0102] Infections account for one of the many complications
associated with surgery and pose tremendous consequences for
patients. During an infection, an infecting agent (e.g., fungi,
micro-organisms, parasites, pathogens (e.g., viral pathogens,
bacterial pathogens, and the like), prions, viroids, viruses, and
the like) generally interferes with the normal functioning of a
biological subject, and causes, in some cases, chronic wounds,
gangrene, loss of an infected tissue, loss of an infected limb, and
occasionally death of the biological subject.
[0103] Implant-associated infections account for a significant
amount of nosocomial infections and despite sterilization and
aseptic procedures, remain as a major impediment to medical
implants including artificial hearts, artificial joints, artificial
prosthetics, breast implants, catheters, contact lens, mechanical
heart valves, subcutaneous sensors, vertebral spacers, and the
like. Implant-associated infections are often difficult to detect,
problematic to cure, and at times expensive to manage. For example,
in cases where the infection does not quickly subside, it sometimes
becomes necessary to remove the implant.
[0104] Implant-associated infections can result from bacterial
adhesion and subsequent biofilm formation proximate an implantation
site. For example, biofilm-forming microorganisms sometimes
colonize implants. Once a biofilm-induced infection takes hold, it
can prove difficult to treat.
[0105] As a non-limiting example, certain systems, devices,
methods, and compositions described herein provide an actively
controllable disinfecting implantable device configured to, for
example, treat or prevent an infection (e.g., an implant-associated
infection, hematogenous implant-associated infection, and the
like), a hematological abnormality, and the like. One non-limiting
approach for treating or preventing an infection, a hematological
abnormality, and the like includes systems, devices, and methods
for administrating a perioperative antibiotic prophylaxis to a
patient. Another non-limiting approach includes systems, devices,
methods, and compositions for actively forming an antimicrobial
agent, in vivo. Another non-limiting approach includes systems,
devices, methods, and compositions for impeding bacterial adherence
to the implant surface. Another non-limiting approach includes
systems, devices, methods, and compositions for actively impeding
biofilm formation on an implant. Another non-limiting approach
includes systems, devices, and methods including coating an implant
with active agent compositions having, for example, anti-biofilm
activity. Another non-limiting approach includes systems, devices,
methods, and compositions for providing an implant with a
scaffold-forming material. Another non-limiting approach includes
systems, devices, and methods including coating an implant with one
or more coatings having self-cleaning properties. Another
non-limiting approach includes systems, devices, and methods
including an implant with a self-cleaning coating having
self-cleaning, and anti-bacterial activity. Another non-limiting
approach includes systems, devices, and methods including an
implant having one or more self-cleaning surfaces.
[0106] For example, in an embodiment the implantable device
includes at least one actively controllable anti-microbial region.
In an embodiment, the actively controllable anti-microbial region
includes at least one actively controllable excitation component,
which may include at least one energy-emitting elements (e.g.,
electric circuits, electrical conductors, electrodes,
electrocautery electrodes, cavity resonators, conducting traces,
ceramic patterned electrodes, electro-mechanical components,
lasers, quantum dots, laser diodes, light-emitting diodes, arc
flashlamps, continuous wave bulbs, ultrasonic emitting elements,
ultrasonic transducers, thermal energy emitting elements,
etc.).
[0107] In an embodiment, the medical device includes a power
source. In an embodiment, the power source includes at least one
piezoelectric material. In an embodiment, the power source includes
at least one alternating-current nanogenerator. For example, a
two-ends-bonded piezoelectric nanowire (e.g., zinc) is subjected to
a periodic mechanical stretching and releasing, the
mechanical-electric coupling effect of the nanowire, combined with
the gate effect of the Schottky contact at the interface, results
in an alternating flow of the charge in the external circuit. See,
Li, et al., Adv. Mater. Vol. 22, pp. 1-4 (2010), which is
incorporated herein by reference.
[0108] In an embodiment, at least one of the inner surface or the
outer surface of the body structure includes at least one tunable
static or dynamic contact angle anisotropy on gradient microscale
patterned topography. See, Long, et al., Langmuir Abstract, vol.
25, no. 22, pp. 12982-12989 (2009), which is incorporated herein by
reference. For example, translationally symmetric topographies are
designed to induce anisotropy of static or dynamic contact angles
fabricated out of a polymer (e.g., poly (dimethyl siloxane)
elastomer). Id.
Microorganisms Associated with Catheter Use
[0109] A catheter device is described herein for detecting and
treating microorganisms in at least one of a plurality of
anti-microbial regions of the body structure of the catheter.
Examples of catheters include but are not limited to intravascular
catheters, hemodialysis catheters, urinary catheters, peritoneal
dialysis catheters, enteral feeding tubes, gastrostomy tubes,
endotracheal tubes, tracheostomy tubes, and umbilical catheters. An
intravascular catheter can be further designated by the type of
vessel it occupies (e.g., peripheral venous, central venous, or
arterial); its intended life span (e.g., temporary or short-term
versus permanent of long-term); its site of insertion (e.g.,
subclavian, femoral, internal jugular, peripheral, and peripherally
inserted central catheter (PICC)); its pathway from skin to vessel
(e.g., tunneled versus nontunneled); its physical length (e.g.,
long versus short); or some specific characteristic of the catheter
(e.g., presence or absence of a cuff, impregnation with heparin,
antibiotics, or antiseptics, and the number of lumens). See, e.g.,
O'Grady, et al., MMWR Recomm. Rep., 51(RR-10):1-32, 2002, which is
incorporated herein by reference.
[0110] In some instances, a bloodstream infection can occur when
bacteria or other microorganisms travel down a catheter and enter
the blood and/or tissue. Catheter related bloodstream infections
cause considerable morbidity, mortality, and healthcare costs. An
estimated 82,000 catheter related bloodstream infections and up to
28,000 attributable deaths occur in intensive care units annually
at an estimated cost of $45,000 per infection. Over 250,000 cases
of central venous catheter-associated bloodstream infections have
been estimated to occur annually in the hospital setting with an
attributable mortality estimated at 12%-25%. See, e.g., Provonost,
et al., BMJ, 340:c309, 2010; O'Grady, et al., MMWR Recomm. Rep.,
51(RR-10):1-32, 2002, which are incorporated herein by
reference.
[0111] The most common microorganism associated with intravascular
catheters is reportedly coagulase-negative staphylococci accounting
for 37% of isolated causes of hospital acquired bloodstream
infection. Other microorganisms associated with intravascular
catheter biofilms and hospital acquired bloodstream infections
include bacteria, e.g., Staphylococcus epidermidis, Staphylococcus
aureus, Pseudomonoas aeruginosa, Klebsiella pneumoniae,
Enterobacteriaceae and Enterococcus faecalis and fungi, e.g.,
Candida albicans and other Candida species. Microorganisms commonly
contaminating urinary catheters films include S. epidermidis,
Enterococcus faecalis, E. coli, Proteus mirabilis, P. aeruginosa,
K. pneumoniae, and other gram-negative organisms. Donlan, Emerging
Infectious Diseases, 7:277-281, 2001; O'Grady, et al., MMWR Recomm.
Rep., 51(RR-10):1-32, 2002, which are incorporated herein by
reference
[0112] Of particular concern are emerging multi-drug resistant
gram-negative bacteria for which there are increasingly fewer
effective antibiotics. Gram negative bacteria accounted for 14% of
catheter-associated bloodstream infections during the period
spanning 1992-1999. An increasing percentage of ICU-related
bacterial isolates contain Enterobacteriaceae that produce extended
spectrum beta-lactamases, particularly Klebsiella pneumonia, which
tend to be resistant to extended spectrum cephalosporins and broad
spectrum antimicrobial agents. Examples of gram-negative bacteria
associated with hospital acquired bacterial infections include but
are not limited to Pseudomonas aeruginosa, Escherichia coli,
Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter spp.,
Serratia marcescens, Enterobacter aerogenes, Stenotrophomonas
maltophilia, Proteus mirabilis, Klebsiella oxytoca, and Citrobacter
freundii. See, e.g., Lockhart et al., J. Clin. Microbiol.,
45:3352-3359, 2007, which is incorporated herein by reference.
Antibiotics for use in treating gram-negative bacteria include but
are not limited to carbapenems, exemplified by imipenem and
meropenem. Multidrug resistance of gram-negative bacteria is
defined as resistance to at least one extended-spectrum
cephalosporin, one aminoglycoside, and ciprofloxacin and is
increasing among isolates of Acinetobacter spp., P. aeruginosa, K.
pneumoniae, and E. cloacae. Colistin and polymyxin B can be used to
treat gram-negative bacterial infection. These drugs were largely
abandoned sometime ago due to kidney and nerve damage, but because
of their infrequent use, bacteria have not had an opportunity to
develop resistance to them at present. See, e.g., Peleg &
Hooper, N. Engl. J. Med., 362:1804-1813, 2010, which is
incorporated herein by reference.
[0113] The types of organisms that most commonly cause
hospital-acquired blood stream infections change over time. During
1986-1989, for example, coagulase-negative staphylococci and
Staphylococcus aureus were the most frequently reported causes of
bloodstream infections, accounting for 27% and 16% of bloodstream
infections, respectively. From 1992 to 1999, coagulase-negative
staphylococci and enterococci were the most frequently isolated
causes of hospital acquired bloodstream infections.
Coagulase-negative staphylococci accounted for 37% and S. aureus
accounted from 12.6% BSIs. By 1999, >50% of all S. aureus
isolated from ICUs were resistant to oxacillin. In 1999,
enterococci accounted for 13.5% of BSIs with vancomycin resistance
escalating from 0.5% in 1989 to 25.9% in 1999. Candida spp. caused
8% of hospital-acquired BSIs reported during 1986-1989 and during
1992-1999. Resistance of Candida spp. to commonly used antifungal
agents is increasing. For example, 10% of C. albicans bloodstream
isolates from hospital patients were resistant to fluconazole.
Additionally 48% of Candida BSIs were caused by nonalbicans species
including C. glabrata and C. krusei which are more likely to
exhibit fluconazole resistance. See, e.g., O'Grady, et al., MMWR
Recomm. Rep., 51(RR-10):1-32, 2002, which is incorporated herein by
reference.
Pathogenesis
[0114] The most common route of infection for peripherally
inserted, short-term catheters is migration of microorganisms
associated with the patient's skin at the insertion site into the
cutaneous catheter tract with subsequent colonization of the
catheter tip. Contamination of the catheter hub contributes
substantially to intraluminal colonization of long-term catheters
by microorganisms. Occasionally, catheters might become
hematogenously seeded from another focus of infection. Rarely,
contamination of an infusate leads to catheter related bloodstream
infections.
[0115] There are a number of important determinants of
catheter-related infection including the material from which the
device is made and the intrinsic virulence factors of the infecting
microorganism. Catheters made of polyvinyl chloride or polyethylene
appear to be less resistant to the adherence of microorganisms than
are catheters made of Teflon, silicone elastomer, or polyurethane.
Surface irregularities of some catheter materials can also enhance
the microbial adherence of certain species (e.g.,
coagulase-negative staphylococci, Acinetobacter calcoaceticus, and
Pseudomonas aeruginosa) and catheters made from these materials are
especially vulnerable to microbial colonization and subsequent
infection. In addition, some catheter materials are more
thrombogenic than others, a characteristic that may predispose to
catheter colonization and catheter-related infection. This
association has led to emphasis on preventing catheter-related
thrombus as an additional mechanism for reducing catheter-related
bloodstream infections and inclusion of anticoagulant flush
solutions in the treatment regimen. The adherence properties of a
given microorganism also are important in the pathogenesis of
catheter-related infection. In general, coagulase-negative
staphylococci adhere to polymer surfaces more readily than do other
pathogens and certain strains of coagulase-negative staphylococci
produce an extracellular polysaccharide often referred to as
"slime". This slime potentiates the pathogenicity of
coagulase-negative staphylococci by allowing the bacteria to
withstand host defense mechanisms (e.g., acting as a barrier to
engulfment and killing by polymorphonuclear lymphocytes) or by
making them less susceptible to antimicrobial agents (e.g., forming
a matrix that binds antimicrobials before their contact with the
organism cell wall). As another example, S. aureus can adhere to
host proteins (e.g., fibronectin) commonly present on catheters.
Certain Candida spp., in the presence of glucose-containing fluids,
can produce slime similar to that of their bacterial counterparts,
potentially explaining the increased proportion of bloodstream
infections caused by fungal pathogens among patients receiving
parenteral nutrition fluids. See, e.g., O'Grady, et al., MMWR
Recomm. Rep., 51(RR-10):1-32, 2002, which is incorporated herein by
reference.
Sensors for Sensing Microorganisms on Catheter
[0116] The catheter device includes at least one sensor configured
to detect the presence of at least one microorganism in at least
one of a plurality of anti-microbial regions on the body structure
of the device. The at least one sensor includes at least one of a
plasmon sensor, pH sensor, temperature sensor, piezoelectric
sensor, electrostrictive sensor, magnetostrictive sensor,
biochemical sensor, optical sensor, or electronic sensor. Sensors
can be incorporated directly onto the inner or outer surface of the
catheter body structure. In an embodiment, the sensor is located in
microchannels incorporated into the inner and/or outer surface of
the catheter body structure, providing a localized measurement
chamber. See, e.g., U.S. Patent Applications 2008/0214909;
2009/0297574; which are incorporated herein by reference.
[0117] In an aspect, the at least one sensor can be a plasmon
sensor configured to detect at least one microorganism based on
changes in the refractive index on the sensor surface in response
to interaction of the microorganism with the sensor. In an aspect,
the surface of the sensor is a glass support or other solid support
coated with a thin film of metal, for example, gold. The sensor
surface can include a matrix to which is immobilized one or more
binding agents configured to recognize at least one microorganism.
The binding agents can be antibodies or fragments thereof,
oligonucleotide or peptide based aptamers, receptors or ligands,
artificial binding substrates formed by molecular imprinting, or
any other examples of molecules and or substrates that bind
microorganisms. As a microorganism moves along the inner or outer
surface of the catheter device, the microorganism interacts with
binding agents on the surface of the sensor. The sensor is
illuminated with a light source, e.g., a light emitting diode or
optical fiber. Resonance occurs at a specific angle of incident
light and is dependent on the concentration of microorganisms on
the surface. See, e.g., Barlen, et al., Sensors, 7:1427-1446, 2007;
Taylor, et al., "Surface plasmon resonance (SPR) sensors for the
detection of bacterial pathogens," in Principles of Bacterial
Detection: Biosensors, Recognition Receptors and Microsystems, ed.
M. Zourob, S. Elwary, & A. Turner, pp. 83-108, 2008, Springer
New York; and Kashyap & Nemova, J. Sensors, 2009:Article ID
645162, which are incorporated herein by reference.
[0118] The one or more sensors can be one or more label-free
optical biosensors that incorporate other optical methodologies,
e.g., interferometers, waveguides, fiber gratings, ring resonators,
and photonic crystals. See, e.g., Fan, et al., Anal. Chim. Acta
620:8-26, 2008, which is incorporated herein by reference.
[0119] In an aspect, the catheter device can include at least one
impedance based sensor configured to detect a microorganism based
on changes in electrical impedance. The sensor can include a
measurement chamber, e.g., a microfluidics channel, incorporated
into the inner or outer surface of the catheter device, with at
least one surface functionalized with a binding agent, e.g.,
antibodies, specific for one or more components of a microorganism.
Microorganisms entering the measurement chamber by diffusion and/or
surface migration bind to the functionalized chamber surface. The
cell membrane of the entrapped microorganism acts as an insulator
at low alternating current frequency and produces a measureable
change in the impedance within the chamber. Microorganisms may be
detected based on volume using electrical impedance as commonly
practiced using a Coulter counter. A MEMS resembling a miniaturized
Coulter counter can be incorporated into the device described
herein and can be constructed using thin platinum electrodes with a
sensing zone of, for example, 20-100 microns (see, e.g., Zheng et
al. (2006) Proceedings of 2006 International Conference on
Microtechnologies in Medicine and Biology, IEEE, Okinawa, Japan,
9-12 May, 2006; Gao et al. (2003) Proceedings of the 25.sup.th
Annual International Conference of the IEEE EMBS, Cancun, Mexico,
Sep. 17-21, 2003), which is incorporated herein by reference.
[0120] In an aspect, the at least one sensor can incorporate
electrochemical impedance spectroscopy. Electrochemical impedance
spectroscopy can be used to measure impedance across a natural
and/or artificial lipid bilayer. The sensor can incorporate an
artificial bilayer that is tethered to the surface of a solid
electrode. One or more receptors, e.g., ion channels, can be
embedded into the lipid bilayer and configured to open and close in
response to binding of a specific microorganism. The open and
closed states can be quantitatively measured as changes in
impedance across the lipid bilayer. See, e.g., Yang, et al., IEEE
SENSORS 2006, EXCO, Daegu, Korea/Oct. 22-25, 2006, which is
incorporated herein by reference. Other examples of impedance-based
sensors for detecting bacteria and fungi are reviewed in Heo &
Hua, Sensors, 9:4483-4502, 2009, which is incorporated herein by
reference.
[0121] In an aspect, the at least one sensor can include a parallel
set of electrode configuration like interdigitated array (IDA)
microelectrodes. An IDA sensor consists of a pair of microcomb
array electrodes functionalized with a binding agent, e.g.,
microorganism selective antibody. A large number of parallel
electrodes can be used to improve detection. An IDA sensor can be
placed in a microfluidic channel using photolithographic
techniques. Binding of a microorganism, e.g., bacteria, on the
surface of the array of electrodes alters both current flow and
capacitance between the neighboring electrodes, causing a
measurable impedance change in a frequency-dependent manner. See,
e.g., Heo & Hau, Sensors, 9:4483-4502, 2009, which is
incorporated herein by reference.
[0122] In an aspect, the at least one sensor can include a
microcantilever configured to detect changes in cantilever bending
or vibrational frequency in response to binding of one or more
microorganisms to the surface of the sensor. In an aspect the
sensor can be bound to a microcantilever or a microbead as in an
immunoaffinity binding array. In another aspect, a biochip can be
formed that uses microcantilever bi-material formed from gold and
silicon, as sensing elements. See, e.g. Vashist J. Nanotech Online
3:DO: 10.2240/azojono0115, 2007, which is incorporated herein by
reference. The gold component of the microcantilever can be
functionalized with one or more binding elements configured to bind
one or more microorganisms. Aptamers or antibodies specific for one
or more microorganisms can be used to functionalize the
microcantilevers. See, e.g., U.S. Pat. No. 7,097,662, which is
incorporated herein by reference. A number of microcantilever
deflection detection methods can be used to measure microorganism
binding including, among other things, piezoresistive deflection
detection, optical deflection detection, capacitive deflection
detection, interferometry deflection detection, optical diffraction
grating deflection detection, and charge coupled device detection.
In some aspects, the one or more microcantilever can be a
nanocantilever with nanoscale components. The one or more
microcantilevers and/or nanocantilevers can be arranged into arrays
for detection of one or more target cells. Both microcantilevers
and nanocantilevers can find utility in microelectromechnical
systems (MEMS) and/or nanoelectromechnical systems (NEMS).
[0123] In an aspect, catheter device can include a field effect
transistor (FET) based biosensor, in which a change in electrical
signal is used to detect interaction of one or more microorganisms
with one or more components of the sensor. See, e.g., U.S. Pat. No.
7,303,875, which is incorporated herein by reference. An example
includes the use of carbon nanotubes functionalized with a
microorganism-specific binding agent. See, e.g., Zelada-Guillen, et
al., Angew. Chem. Int. Ed., 48:7334-7337, 2009, which is
incorporated herein by reference. Single walled carbon nanotubes
can act as efficient ion-to-electron transducers in potentiometric
analysis. The carbon nanotubes can be functionalized with a binding
agent, e.g., an oligonucleotide aptamer, configured to selectively
bind one or more microorganisms. The binding agent is modified with
an amine group and covalently immobilized onto a layer of
previously carboxylated single-walled carbon nanotubes. The
aptamers are self-assembled on the carbon nanotubes through
stacking interactions between the purine and pyrimidine bases of
the oligonucleotide aptamers and the walls of the carbon nanotubes.
Upon microorganism binding to the aptamer, the aptamers change
conformation, separating the phosphate groups of the aptamer from
the side-walls of the carbon nanotubes and inducing a charge change
to the carbon nanotube and recorded potential. Carbon nanotubes can
be used to form composites with silicone, polyurethane, and
poly(vinyl) chloride, materials commonly used in production of
medical catheters. See, e.g., Xanthos, "Polymers and Polymer
Composites," in Functional Fillers for Plastics, ed. M. Xanthos,
2010, pp. 3-18, WILEY-VCH Verlag GMBH & Co. KGaA, Weinheim;
U.S. Patent Applications 2009/0012610 and 2010/0104652, which is
incorporated herein by reference.
[0124] In a further aspect, the catheter device can include at
least one sensor that relies on optical imaging to sense one or
more microorganisms. The microorganisms may be sensed using any of
a number of imaging or optical methods including among other things
light scattering, electrical impedance, infrared spectroscopy,
acoustic imaging, thermal imaging, photothermal imaging, visible
light absorption and refraction, and autofluorescence. See, e.g.,
U.S. Patent Application 2009/0093728; Doornbos et al. Cytometry
14:589-594, 1993; Gao et al. Proceedings of the 25.sup.th Annual
International Conference of the IEEE EMBS, Cancun, Mexico, Sep.
17-21, 2003; Oberreuter et al. Int. J. Syst. Evol. Microbiol.
52:91-100, 2002; Baddour et al. Ultrasonics Symposium IEEE
2:1639-1644, 2002; Zharov et al. J. Cell. Biochem. 97:916-932,
2006; Zharov et al. J. Biomed. Opt. 11:054034-1-4, 2006; Koenig et
al. J. Fluoresc. 4:17-40, 1994; which are each incorporated herein
by reference
[0125] In another aspect, the device can include at least one
sensor configured to detect microorganisms based on
autofluorescence. A microorganism can be detected by
autofluorescence induced by electromagnetic energy. Naturally
occurring autofluorescence in bacteria is derived from biomolecules
containing fluorophores, such as porphyrins, amino acids
tryptophan, tyrosine, and phenylalanine, and the coenzymes NADP,
NADPH, and flavins. See, e.g., Koenig et al. J. Fluoresc. 4:17-40,
1994 which is incorporated herein by reference. Bacteria can be
detected using fluorescence lifetimes measured at 280-540 nm after
excitation at 250-450 nm (Bouchard et al. J. Biomed. Opt.
11:014011, 2006, which is incorporated herein by reference). For
example, Streptococcus pneumoniae, can be detected using
fluorescence spectroscopy at excitation wavelengths of 250 and 550
nm and emission wavelengths of 265 and 700 nm (Ammor J. Fluoresc.
17:455-459, 2007, which is incorporated herein by reference).
Autofluorescence may also be used to detect members of the fungi
family. Candida albicans and Aspergillus niger autofluoresce at
wavelengths ranging from 515 nm to 560 nm when irradiated with
electromagnetic energy at wavelengths of 465-495 nm. See, e.g.,
Mateus et al. Antimicrob. Agents and Chemother. 48:3358-3336, 2004;
Sage et al. American Biotechnology Laboratory 24:20-23, 2006, which
are incorporated herein by reference. Autofluorescence associated
with the food vacuole of the malaria parasite Plasmodium spp. can
used to detect infected red blood cells within the blood stream.
See, e.g., Wissing et al. J. Biol. Chem. 277:37747-37755, 2002,
which is incorporated herein by reference.
[0126] In an aspect, the catheter device includes at least one
sensor configured to detect a microorganism based on changes in
fluorescent signaling. The sensor can include a charged coupled
device (CCD) or complementary metal-oxide-semiconductor (CMOS)
sensor in combination with a binding agent that exhibits altered
optical, e.g., fluorescence, properties in response to binding a
microorganism. In an aspect, the sensor can include a one-chip CMOS
detector and light emitting diode for exciting and measuring
fluorescence associated with the sensor. See, e.g., Tamura, et al.,
J. Neurosci. Methods, 173:114-120, 2008, which is incorporated
herein by reference.
[0127] In an aspect, the at least one sensor includes a binding
molecule, e.g., an antibody or oligonucleotide aptamer, configured
to exhibit Forster or fluorescence resonance energy transfer (FRET)
in response to binding one or more microorganisms. FRET is a
distance-dependent interaction between the electronic excited
states of two fluorophore molecules in which excitation is
transferred from a donor molecule to an acceptor molecule without
emission of a photon. For use in a sensor, one or more binding
molecules, e.g., antibodies or oligonucleotide aptamers, associated
with the one or more sensors are configured with at least one donor
molecule and at least one acceptor molecule. The interaction of a
metabolic analyte with the binding molecule of the sensor results
in a conformation change in the binding molecule, leading to
changes in the distance between the donor and acceptor molecules
and changes in measurable fluorescence.
[0128] A variety of donor and acceptor fluorophore pairs can be
considered for FRET including, among other things, fluorescein and
tetramethylrhodamine; IAEDANS and fluorescein; fluorescein and
fluorescein; and BODIPY FL and BODIPY FL, and various Alexa Fluor
pairings as described herein. The cyanine dyes Cy3, Cy5, Cy5.5 and
Cy7, which emit in the red and far red wavelength range (>550
nm) as well as semiconductor quantum dots can also be used for
FRET-based detection systems. Quenching dyes can also be used to
quench the fluorescence of visible light-excited fluorophores,
examples of which include DABCYL, the non-fluorescing
diarylrhodamine derivative dyes QSY 7, QSY 9 and QSY 21 (Molecular
Probes, Carlsbad, Calif., USA), the non-fluorescing Black Hole
Quenchers BHQ0, BHQ1, BHQ2, and BHQ3 (Biosearch Technologies, Inc.,
Novato, Calif., USA) and Eclipse (Applera Corp., Norwalk, Conn.,
USA). A variety of donor fluorophore and quencher pairs can be
considered for FRET associated with the binding molecule including,
among other things, fluorescein with DABCYL; EDANS with DABCYL; or
fluorescein with QSY 7 and QSY 9. In general, QSY 7 and QSY 9 dyes
efficiently quench the fluorescence emission of donor dyes
including blue-fluorescent coumarins, green- or orange-fluorescent
dyes, and conjugates of the Texas Red and Alexa Fluor 594 dyes. QSY
21 dye efficiently quenches all red-fluorescent dyes. A number of
the Alexa Fluor (AF) fluorophores (Molecular Probes-Invitrogen,
Carlsbad, Calif., USA) can be paired with quenching molecules as
follows: AF 350 with QSY 35 or DABCYL; AF 488 with QSY 35, DABCYL,
QSY7 or QSY9; AF 546 with QSY 35, DABCYL, QSY7 or QSY9; AF 555 with
QSY7 or QSY9; AF 568 with QSY7, QSY9 or QSY21; AF 594 with QSY21;
and AF 647 with QSY 21.
Possible Microorganism Specific Biomolecules Recognized by Catheter
Associated Sensors
[0129] In an aspect, the catheter device includes at least one
sensor configured to detect a microorganism. The at least one
sensor can be configured to detect at least one component of at
least one microorganism. The at least one component of a
microorganism can include at least one of a lipid, peptide,
polypeptide, glycolipid, proteoglycan, lipoprotein, glycoprotein,
glycopeptide, metalloprotein, enzyme, carbohydrate, cytokine,
microorganism cell membrane, microorganism cell receptor, or other
microorganism component. For example, the sensor can be configured
to detect at least one component of the outer membrane, cell wall,
and/or cytoplasmic membrane of bacteria. Components of bacterial
cell walls include peptidoglycan, a mesh-like polymer of N-acetyl
glucosamine, N-acetyl muramic acid and amino acids, most commonly
L-alanine, D-alanine, D-glutamic acid, and diaminopimelic acid. The
cell wall of Gram-positive bacteria contains a thick layer of
peptidoglycan that encircles the cell and further includes teichoic
acid, a phosphodiester polymer of glycerol or ribitol joined by
phosphate groups. In contrast, the cell wall of Gram-negative
bacteria contains a thin layer of peptidoglycan separating the
cytoplasmic membrane and the outer membrane. The cell wall of
gram-negative bacteria further includes Braun's lipoprotein, which
is covalently linked to the peptidoglycan and extends a hydrophobic
anchor into the lipid bilayer of the outer membrane. Components of
the outer membrane of Gram-negative bacteria include, but are not
limited to, lipids, proteins, and lipopolysaccharides.
Lipopolysaccharides are composed of Lipid A, a conserved core
polysaccharide, and a highly variable O-polysaccharide. Proteins
associated with the outer membrane include the OMP (outer membrane
protein) porins, exemplified by OmpC, OmpF and PhoP of E. coli.
[0130] The at least one sensor can be configured to detect
components of the inner bacterial cytoplasmic membrane including,
but are not limited to, the MPA1-C (also called polysaccharide
copolymerase, PCP2a) family of proteins, the MPA2 family of
proteins, and the ABC bacteriocin exporter accessory protein (BEA)
family of proteins. Other examples of components of bacteria
include, but are not limited to, transporters, e.g., sugar porter
(major facilitator superfamily), amino-acid/polyamine/organocation
(APC) superfamily, cation diffusion facilitator,
resistance-nodulation-division type transporter, SecDF,
calcium:cation antiporter, inorganic phosphate transporter,
monovalent cation:proton antiporter-1, monovalent cation:proton
antiporter-2, potassium transporter, nucleobase:cation symporter-2,
formate-nitrite transporter, divalent anion:sodium symporter,
ammonium transporter, and multi-antimicrobial extrusion; channels,
e.g., major intrinsic protein, chloride channel, and metal ion
transporter; and primary active transporters, e.g., P-type ATPase,
arsenite-antimonite efflux, Type II secretory pathway (SecY), and
sodium-transporting carboxylic acid decarboxylase. A number of
other components of bacteria have been described in Chung, et al.,
J. Bacteriology 183:1012-1021, 2001, which is incorporated herein
by reference.
[0131] In an aspect, the catheter device includes at least one
sensor configured to sense one or more components on the outer
surface of a pathogenic fungus, examples of which include Candida
albicans, Candida glabrata, and Asperigillus species. The cell wall
of most fungi is composed of glycoproteins embedded within a
polysaccharide matrix or scaffolding. Additionally, some fungal
species produce a polysaccharide capsule that surrounds the cell
wall (e.g., the glucuronoxylomannan capsule produced by
Cryptococcus neoformans). In certain instances, carbohydrates are
the first fungal components to contact the host tissue.
Carbohydrate chains or glycans within the cell wall of fungi are
composed of various combinations and derivatives of three
monosaccharides: D-glucose, N-acetyl-D-glucosamine, and D-mannose.
The cell envelope of Candida albicans, for example, contains highly
branched polymers of glucose (glucan), linear polymers of
N-acetyl-D-glucosamine (chitin), and mannose (mannan) incorporated
into various glycoproteins. Sialic acid may also be a component of
the fungal cell wall. See, e.g., Masuoka, Clin. Microbiol. Rev.
17:281-310, 2004, which is incorporated herein by reference.
[0132] In an aspect, the at least one sensor can be configured to
sense one or more components secreted by a microorganism. Examples
include various membrane-active peptides and exotoxins, in
particular those produced by bacteria, for example, pneumolysins
secreted by streptococci and alpha-toxin a major cytolysin secreted
by Staphylococcus aureus. Other examples of toxins secreted by S.
aureus include toxic shock syndrome toxin-1, enterotoxins,
leukicidins, and phenyl-soluble modulins. Secretion of pore-forming
exotoxins by bacteria is abundant and endotoxins, such as
lipopolysaccharides (LPS). Examples of pore-forming toxins include
but are not limited to perfringiolysin, hemolysin, listeriolysin,
alpha toxin, pneumolysin, streptolysin O, and leukocidin. Examples
of pyrogenic exotoxins include but are not limited to
staphylococcal enterotoxins serotypes A-E, G, and H; group A
streptococcal pyrogenic exotoxins A-c; staphylococcal exfoliatin
toxin; and staphylococcal toxic shock syndrome toxin-1. Other
toxins include exotoxin A (Pseudomonas aeruginosa). Examples of
toxins secreted by other microorganisms include fungal toxins such
as, for example, aflatoxin and gliotoxin secreted by Aspergillus
species.
[0133] In an aspect, the catheter device can include at least one
sensor configured to differentiate between microorganisms based on
detecting distinguishing components specific for a given
microorganism. For example, Gram-positive bacteria can be
differentiated from Gram-negative bacteria based on detection of
lipoteichoic acid, the latter of which is expressed on the
Gram-positive bacteria Listeria monocytogenes, Streptococcus
pneumoniae, Staphylococcus aureus, and Staphylococcus epidermidis.
Gram-negative bacteria can be detected based on detection of
lipopolysaccharides. In general, reagents, e.g., antibodies, that
can distinguish between components of Gram-positive and
Gram-negative bacteria can be developed using standard methods or
are commercially available (from, e.g., Santa Cruz Biotechnology,
Inc., Santa Cruz, Calif.; Novus Biologicals, LLC, Littleton, Colo.;
GenWay Biotech, Inc., San Diego, Calif.). Fungi can be
distinguished from bacteria based on the detection of glucan,
chitin, mannan, or combinations thereof. For example, Sendid, et
al., describe development of antibodies against glucan, chitin and
mannan for detection of Candida albicans (in, Clin. Vaccine
Immunol., 15:1868-1877, 2008, which is incorporated herein by
reference).
Binding Agents Specific for Recognition Targets
[0134] The at least one sensor can include at least one binding
agent configured to bind a component of a microorganism. The at
least one binding agent for selectively binding a component of a
microorganism can include, but is not limited to, antibodies,
antibody fragments, peptides, oligonucleotides, DNA, RNA, aptamers,
protein nucleic acids, proteins, receptors, receptor ligands,
lectins, an artificial binding substrate formed by molecular
imprinting, or other examples of binding agents configured to bind
microorganisms.
[0135] The at least one binding agent associated with the sensor(s)
include, but is not limited to, antibodies configured to bind one
or more components of a microorganism. Antibodies or fragments
thereof for use as one or more binding agents can include, but are
not limited to, monoclonal antibodies, polyclonal antibodies, Fab
fragments of monoclonal antibodies, Fab fragments of polyclonal
antibodies, Fab.sub.2 fragments of monoclonal antibodies, and
Fab.sub.2 fragments of polyclonal antibodies, chimeric antibodies,
non-human antibodies, fully human antibodies, among others. Single
chain or multiple chain antigen-recognition sites can be used.
Multiple chain antigen-recognition sites can be fused or unfused.
Antibodies or fragments thereof can be generated using standard
methods. See, e.g., Harlow & Lane (Antibodies: A Laboratory
Manual, Cold Spring Harbor Laboratory Press; 1.sup.st edition
1988), which is incorporated herein by reference.
[0136] Alternatively, an antibody or fragment thereof directed
against one or more inflammatory mediators can be generated, for
example, using phage display technology. See, e.g., Kupper, et al.
BMC Biotechnology 5:4, 2005, which is incorporated herein by
reference. An antibody, a fragment thereof, or an artificial
antibody, e.g., Affibody.RTM. artificial antibodies (Affibody AB,
Bromma, Sweden) can be prepared using in silico design (See Knappik
et al., J. Mol. Biol. 296: 57-86, 2000), which is incorporated
herein by reference. In some aspects, antibodies directed against
one or more components of a microorganism may be available from a
commercial source (from, e.g., Novus Biological, Littleton, Colo.;
Sigma-Aldrich, St. Louis, Mo.; United States Biological,
Swampscott, Mass.). Fenelon, et al., describe development of
antibodies specific for three Aspergillus species commonly
associated with human disease; A. fumigatus, A. flavus, and A.
niger (in, J. Clin. Microbiol., 37:1221-1223, 1999, which is
incorporated herein by reference). Sendid, et al., describe
development of antibodies against glucan, chitin and mannan for
detection of Candida albicans (in, Clin. Vaccine Immunol.,
15:1868-1877, 2008, which is incorporated herein by reference)
[0137] The at least one binding agent associated with the sensor(s)
includes but is not limited to, aptamers configured to bind one or
more components of a microorganism. The aptamer can be an
oligonucleotide RNA- or DNA-based aptamer. Aptamers are artificial
oligonucleotides (DNA or RNA) which bind to a wide variety of
entities (e.g., metal ions, small organic molecules, proteins, and
cells) with high selectivity, specificity, and affinity. Aptamers
can be isolated from a large library of 10.sup.14 to 10.sup.15
random oligonucleotide sequences using an iterative in vitro
selection procedure often termed "systematic evolution of ligands
by exponential enrichment" (SELEX). See, e.g., Cao, et al., Current
Proteomics 2:31-40, 2005; Proske, et al., Appl. Microbiol.
Biotechnol. 69:367-374, 2005; Jayasena Clin. Chem. 45:1628-1650,
1999, which are incorporated herein by reference. In general, SELEX
may be used to generate aptamers against microorganisms including
bacteria, fungi and parasites. For example, Cao, et al., describe
using SELEX and whole bacteria to generate a panel of DNA aptamers
configured to detect Staphylococcus aureus (in Nucleic Acids Res.,
37:4621-4628, 2009), which is incorporated herein by reference. For
Gram positive bacteria, teichoic acids and peptidoglycan will serve
as targets. For Gram negative bacteria, common lipopolysaccharide
moieties such as 2-keto-3-deoxyoctanate (KDO antigen) will be
targeted for aptamer development. Similarly, for fungi, cell wall
chitin will be used to select highly specific FRET-aptamers from a
randomized DNA library. Other examples are described in Shangguan,
et al., Proc. Natl. Acad. Sci. USA. 103:11838-11843; Chen, et al.,
Biochem. Biophys. Res. Commun. 357:743-748, 2007; Ulrich, et al.,
J. Biol. Chem. 277:20756-20762, 2002; and Low, et al., Biochem.
Biophys. Res. Commun., 378:701-705, 2009, which are incorporated
herein by reference.
[0138] In an aspect, the at least one binding agent associated with
the sensor(s) include but is not limited to peptide-based aptamers
configured to bind one or more components of a microorganism.
Peptide-based aptamers are artificial proteins in which inserted
peptides are expressed as part of the primary sequence of a
structurally stable protein. See, e.g., Crawford, et al., Brief.
Funct. Genomic Proteomic 2:72-79, 2003, which is incorporated
herein by reference. Peptide-based aptamers can be generated by
screening a target microorganism or parts thereof against yeast
two-hybrid libraries, yeast expression libraries, bacterial
expression libraries and/or retroviral libraries. Peptide-based
aptamers can have binding affinities comparable to antibodies.
[0139] In an aspect, the at least one binding agent associated with
the sensor(s) includes but is not limited to lectins configured to
bind one or more components of a microorganism. While the term
"lectin" was originally used to define agglutinins involved in the
agglutination process, the term "lectin" is currently used more
generally to include sugar-binding proteins. Lectins are able to
recognize specific carbohydrate structures such that even
oligosaccharides with identical sugar compositions can be
distinguished or separated. Some lectins will bind only to
structures with mannose or glucose residues, while others may
recognize only galactose residues. Some lectins require that the
particular sugar is in a terminal non-reducing position in the
oligosaccharide, while others can bind to sugars within the
oligosaccharide chain. As such, specific lectins can be used to
distinguish various microorganisms based on the composition and
pattern of cell surface carbohydrates. For example, Serra, et al.,
describe the use of lectins as binding agents in piezoelectric
biosensors capable of detecting and quantifying Staphylococcus
aureus (in, Anal. Bioanal. Chem., 391:1853-1860, 2008), which is
incorporated herein by reference.
[0140] Examples of lectins include, but are not limited to, algal
lectins, e.g., b-prism lectin; animal lectins, e.g., tachylectin-2,
C-type lectins, C-type lectin-like, calnexin-calreticulin, capsid
protein, chitin-binding protein, ficolins, fucolectin, H-type
lectins, 1-type lectins, sialoadhesin, siglec-5, siglec-7,
micronemal protein, P-type lectins, pentrxin, b-trefoil, galectins,
congerins, selenocosmia huwena lectin-I, Hcgp-39, Ym1; bacterial
lectins, e.g., Pseudomonas PA-IL, Burkholderia lectins,
chromobacterium CV-IIL, Pseudomonas PA IIL, Ralsonia RS-ILL,
ADP-ribosylating toxin, Ralstonia lectin, Clostridium
hemagglutinin, botulinum toxin, tetanus toxin, cyanobacterial
lectins, FimH, GafD, PapG, Staphylococcal enterotoxin B, toxin
SSL11, toxin SSL5; fungal and yeast lectins, e.g., Aleuria aurantia
lectin, integrin-like lectin, Agaricus lectin, Sclerotium lectin,
Xerocomus lectin, Laetiporus lectin, Marasmius oreades agglutinin,
agrocybe galectin, coprinus galectin-2, Ig-like lectins, L-type
lectins; plant lectins, e.g., alpha-D-mannose-specific plant
lectins, amaranthus antimicrobial peptide, hevein, pokeweed lectin,
Urtica dioica UD, wheat germ WGA-1, WGA-2, WGA-3, artocarpin,
artocarpus hirsute AHL, banana lectin, Calsepa, heltuba, jacalin,
Maclura pomifera MPA, MornigaM, Parkia lectins, abrin-a, abrus
agglutinin, amaranthin, castor bean ricin B, ebulin, mistletoe
lectin, TKL-1, cyanovirin-N homolog, and various legume lectins;
and viral lectins, e.g., capsid protein, coat protein, fiber knob,
hemagglutinin, and tailspike protein (see, e.g., E. Bettler, R.
Loris, A. Imberty "3D-Lectin database: A web site for images and
structural information on lectins" 3rd Electronic Glycoscience
Conference, The internet and World Wide Web, 6-17 Oct. 1997; on the
worldwide web at cermav.cnrs.fr/lectines, Sahly, et al., Infect.
Immunity, 78:1322-1332, 2008, which is incorporated herein by
reference.
[0141] The at least one binding agent associated with the sensor(s)
includes but is not limited to, one or more artificial binding
substrates formed by the process of molecular imprinting and
configured to bind one or more components of a microorganism. In
the process of molecular imprinting, a template, e.g., a whole
microorganism or parts thereof, is combined with functional
monomers which, upon cross-linking, form a polymer matrix that
surrounds the template. (See Alexander, et al., J. Mol. Recog.
19:106-180, 2006, which is incorporated herein by reference).
Removal of the template leaves a stable cavity in the polymer
matrix that is complementary in size and shape to the template. In
an aspect, functional monomers of acrylamide and ethylene glycol
dimethacrylate can be mixed with a microorganism or parts thereof,
in the presence of a photoinitiator and ultraviolet irradiation
used to cross-link the monomers. The resulting polymer can be
crushed or ground into smaller pieces and washed to remove the
microorganism or parts thereof, leaving a particulate matrix
material capable of binding the microorganism. For example, Cohen
et al., describe using whole cell imprinting in sol-gel imprinted
films to generate a bacterial sensor (in, Int. J. Mol. Sci.,
11:1236-1252, 2010), which is incorporated herein by reference.
Examples of other functional monomers, cross-linkers and initiators
may be used to generate an artificial binding substrate are
provided. See, e.g., U.S. Pat. No. 7,319,038; Alexander, et al., J.
Mol. Recognit. 19:106-180, 2006, which are incorporated herein by
reference. In a further aspect, hydrogels may be used for molecular
imprinting. See, e.g., Byrne et al., "Molecular imprinting within
hydrogels", Advanced Drug Delivery Reviews, 54: 149-161, 2002,
which is incorporated herein by reference. Other examples of
synthetic binders are provided. See, e.g., U.S. Pat. Nos.
6,255,461; 5,804,563; 6,797,522; 6,670,427; and 5,831,012; and U.S.
Patent Application 20040018508; and Ye and Haupt, Anal Bioanal
Chem. 378: 1887-1897, 2004; Peppas and Huang, Pharm Res. 19:
578-587 2002, which are incorporated herein by reference.
Reservoirs
[0142] In an aspect, the catheter includes at least one
anti-microbial agent reservoir configured to deliver one or more
anti-microbial agents to one or more anti-microbial regions of the
body structure of the catheter. The at least one anti-microbial
agent reservoir can be positioned in one or more sites in at least
one of the outer surface of the body structure, the inner surface
of the body structure, embedded in the body structure itself, or
combinations thereof. In an aspect, the at least one anti-microbial
agent reservoir is in communication with one or more sensors. In an
aspect, the reservoir is configured for controllable delivery of
one or more anti-microbial agents in response to a signal from a
sensor indicative of the presence of a microorganism. In an aspect,
the catheter includes a single anti-microbial agent reservoir with
multiple outlets for delivery of one or more anti-microbial agents
to one or more anti-microbial regions. In an aspect, the catheter
includes multiple anti-microbial agent reservoirs with one or more
outlets for delivery of one or more anti-microbial agents to one or
more anti-microbial regions. In an aspect, the catheter includes
one or more anti-microbial agent reservoirs embedded in one or more
pores in the catheter body structure. See, e.g., U.S. Pat. No.
7,575,593, which is incorporated herein by reference.
[0143] In an aspect, the at least one anti-microbial-agent
reservoir includes at least one outlet with a release mechanism
operably connected to one or more sensors for controllable delivery
of an anti-microbial agent. The release mechanism can include but
is not limited to a valve, a switch, a plug, a cap, or a membrane.
In an aspect, the anti-microbial-agent reservoir includes a valve
for controllable delivery of an anti-microbial agent. Various
examples of micro valves or microelectromechanical systems (MEMS)
valves for controlling fluid flow in micro devices have been
described. See, e.g., Luckevich M. Valve World, May 2007, pp.
79-83; Givrad T K., et al., Proceedings of BIOMed2008, 3.sup.rd
Frontiers in Biomedical Devices Conference. Jun. 18-20, 2008,
Irvine, Calif., USA; U.S. Pat. Nos. 6,612,535; 7,124,773, each of
which is incorporated herein by reference.
[0144] In an aspect, the at least one anti-microbial-agent
reservoir can include at least one outlet covered with a removable
membrane. The membrane can be responsive to a directly applied
stimulus (e.g., an applied voltage or potential) or to a change in
the local environment of the device (e.g., local pH change), or any
of a number of other stimuli including among other things heat,
light (e.g., laser), and magnetic field. See, e.g., U.S. Pat. No.
6,808,522; Grayson, R. et al., Proceedings of IEEE 92:6-21, 2004,
which are each incorporated herein by reference. As an example, the
at least one anti-microbial-agent reservoir can be an array of
microreservoirs on a microchip in which each aliquot of one or more
anti-microbial agents is contained in its own reservoir and capped
by an environmentally sensitive material. In an aspect, the
microreservoirs can be capped with a gold membrane which is
weakened and ruptured by electrochemical dissolution in response to
application of an anode voltage to the membrane in the presence of
chloride ions, resulting in release of contents of the
microreservoir as described in U.S. Pat. No. 5,797,898 and in
Prescott, et al., Nat. Biotech., 24:437-438, 2006, which are
incorporated, herein by reference.
[0145] Alternatively, the microreservoirs can be capped by a
temperature sensitive material which can be ruptured in response to
selective application of heat to one or more of the reservoirs as
described in U.S. Pat. No. 6,669,683, which is incorporated herein
by reference. For example, Elman, et al., describe a multi-layered
temperature-responsive drug delivery system that includes a
reservoir layer containing a drug solution; a membrane layer that
hermetically seals the drug reservoir, and from where the drug is
ejected; and an actuation layer, where bubbles are formed in
response to localized heat application (in, Biomedical
Microdevices, 11:625-631, 2009, which is incorporated herein by
reference). The actuation layer is defined by micro-resistors,
which once actuated, rapidly and locally heat a contained fluid to
generate bubbles. The increase in pressure caused by the bubbles
ruptures the membrane and jets the contained drug solution out of
the device, allowing for rapid drug delivery.
[0146] In an embodiment, the system includes one or more
computer-readable media (e.g., drives, interface sockets, Universal
Serial Bus (USB) ports, memory card slots, input/output components
(e.g., graphical user interface, display, keyboard, keypad,
trackball, joystick, touch-screen, mouse, switch, dial, etc.)).
[0147] In an embodiment, the computer-readable media is configured
to accept signal-bearing media. In an embodiment, a program for
causing the system to execute any of the disclosed methods can be
stored on, for example, a computer-readable recording medium, a
signal-bearing medium, or the like. Examples of signal-bearing
media include, among others, a recordable type medium such as
magnetic tape, floppy disk, hard disk drive, Compact Disc (CD),
Digital Video Disk (DVD), Blu-Ray Disc, digital tape, computer
memory, etc., and transmission type medium (digital and/or analog).
Other non-limiting examples of signal bearing media include, for
example, DVD-ROM, DVD-RAM, DVD+RW, DVD-RW, DVD-R, DVD+R, CD-ROM,
Super Audio CD, CD-R, CD+R, CD+RW, CD-RW, Video Compact Discs,
Super Video Discs, flash memory, magnetic tape, magneto-optic disk,
MINIDISC, non-volatile memory card, EEPROM, optical disk, optical
storage, RAM, ROM, system memory, web server, etc.
[0148] In an aspect, the at least one anti-microbial agent
reservoir can be configured to include a release mechanism that is
a natural and/or synthetic stimulus-responsive hydrogel or polymer
which changes conformation rapidly and reversibly in response to
environmental stimuli such as, for example, temperature, pH, ionic
strength, electrical potential, light, magnetic field or
ultrasound. See, e.g., U.S. Pat. No. 5,226,902; and Stubbe, et al.,
Pharmaceutical Res., 21:1732-1740, 2004, which are incorporated
herein by reference. Examples of polymers are described in U.S.
Pat. Nos. 5,830,207; 6,720,402; and 7,033,571, which are
incorporated herein by reference. For example, a hydrogel or other
polymer or other smart material may be used as an environmentally
sensitive actuator to control flow of an agent out of an
implantable device as described in U.S. Pat. Nos. 6,416,495;
6,571,125; and 6,755,621, which are incorporated herein by
reference. As such, the at least one anti-microbial agent reservoir
can incorporate a hydrogel or other polymer that modulates delivery
of one or more anti-microbial agents in response to a trigger from
a sensor.
[0149] The anti-microbial agent reservoirs can include one or more
target-responsive microparticles attached to the catheter device in
at least one of a plurality of regions and configured to release
one or more anti-microbial agent upon interaction with a
microorganism. The one or more target-responsive microparticles can
include one or more binding elements incorporated into the
microparticles and configured to bind at least one microorganism
component. Examples of binding elements include but are not limited
to antibodies, aptamers, oligonucleotides, protein nucleic acids,
receptors, ligands, lectins, synthetic binding moieties, molecular
imprinting, or combinations thereof. Binding of a microorganism to
the microparticles changes the properties of the microparticle and
allows for release of an encapsulated anti-microbial agent. For
example, Yang et al. describe target-responsive microparticles
which include a target-specific aptamer, two additional overlapping
oligonucleotides linked to polymerized acrylamide, and an
encapsulated material. Binding of a target to the target-specific
aptamer disrupts the interaction of the overlapping
oligonucleotides causing aggregates of polymerized acrylamide to
separate from one another and allowing for release of the
encapsulated material. See, e.g., Yang et al., J. Am. Chem. Soc.,
130:6320-6321, 2008; and Gu, et al., Proc. Natl. Acad. Sci., USA,
105:2586-2591, 2008, which are incorporated herein by reference. In
another example, Miyata, et al., describe target-responsive
hydrogels prepared by molecular imprinting in which ligands
reactive with a target, such as, for example, lectins and/or
antibodies, are conjugated with acrylate and polymerized with
acrylamide to form a target-responsive hydrogel (Proc. Natl. Acad.
Sci., USA, 103:1190-1193, 2006, which is incorporated herein by
reference).
[0150] The one or more microparticles can include
temperature-responsive microparticles configured to release an
encapsulated anti-microbial agent in response to changes in
temperature. In this instance, the change in temperature can
include elevated endogenous temperature of the subject either
globally due to a fever or locally due to inflammation, ischemia,
or neoplastic tissue. The change in temperature can also include
application of an energy source to the catheter to induce a
localized increase in temperature. Temperature-responsive
microparticles can include thermally sensitive lipid-based and/or
polymer-based micelles. The micelles can be configured to
encapsulate one or more anti-microbial agents and remain stable
until a critical solution temperature (LCST) has been reached. For
example, micelles fabricated from
poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide--
co-glycolide) are stable at 37.degree. C. but begin to release
their contents at a LCST of 39.degree. C. See, e.g., Liu, et al.,
Mol. BioSyst., 1:158-165, 2005, which is incorporated herein by
reference. Temperature-responsive micelles composed of
N-(2-hydroxypropyl)methyl acrylamide (lactate) and optionally
polyethylene glycol have also been described. See, e.g., U.S. Pat.
No. 7,425,581, which is incorporated herein by reference. Examples
of other polymers for use in generating temperature-responsive
microparticles include but are not limited to
poly(N-(3-ethoxypropyl)acrylamide), dimethylaminoethyl
methacrylate, ethylene glycol dimethacrylate, and N-isopropyl
acrylamide. See, e.g., U.S. Pat. No. 6,451,429, which is
incorporated herein by reference.
Anti-Microbial Agents
[0151] Further non-limiting examples of anti-microbial agent
include compounds, molecules, or treatments that elicit a
biological response from any biological subject. Further
non-limiting examples of anti-microbial agents include active
agents (e.g., antimicrobial active agents), pharmaceuticals (e.g.,
a drug, a therapeutic compound, pharmaceutical salts, and the like)
non-pharmaceuticals (e.g., a cosmetic substance, and the like),
nutraceuticals, antioxidants, phytochemicals, homeopathic agents,
and the like. Further non-limiting examples of anti-microbial
agents include peroxidases (e.g., haloperoxidases such as
chloroperoxidase, and the like), oxidoreductase (e.g.,
myeloperoxidase, eosinophil peroxidase, lactoperoxidase, and the
like) oxidases, and the like.
[0152] Further non-limiting examples of anti-microbial agents
include one or more pore-forming toxins. Non-limiting examples of
pore-forming toxins include beta-pore-forming toxins, e.g.,
hemolysin, Panton-Valentine leukocidin S, aerolysin, Clostridial
epsilon-toxin; binary toxins, e.g., anthrax, C. perfringens lota
toxin, C. difficile cytolethal toxins; cholesterol-dependent
cytolysins; pneumolysin; small pore-forming toxins; and gramicidin
A.
[0153] Further non-limiting examples of anti-microbial agents
include one or more pore-forming antimicrobial peptides.
Antimicrobial peptides represent an abundant and diverse group of
molecules that are naturally produced by many tissues and cell
types in a variety of invertebrate, plant and animal species. The
amino acid composition, amphipathicity, cationic charge and size of
antimicrobial peptides allow them to attach to and insert into
microbial membrane bilayers to form pores leading to cellular
disruption and death. More than 800 different antimicrobial
peptides have been identified or predicted from nucleic acid
sequences, a subset of which have are available in a public
database (see, e.g., Wang & Wang, Nucleic Acids Res.
32:D590-D592, 2004); on the worldwide web at
asp.unmc.edu/AP/main.php, which is incorporated herein by
reference). More specific examples of antimicrobial peptides
include, but are not limited to, anionic peptides, e.g., maximin H5
from amphibians, small anionic peptides rich in glutamic and
aspartic acids from sheep, cattle and humans, and dermcidin from
humans; linear cationic alpha-helical peptides, e.g., cecropins
(A), andropin, moricin, ceratotoxin, and melittin from insects,
cecropin P1 from Ascaris nematodes, magainin (2), dermaseptin,
bombinin, brevinin-1, esculentins and buforin II from amphibians,
pleurocidin from skin mucous secretions of the winter flounder,
seminalplasmin, BMAP, SMAP (SMAP29, ovispirin), PMAP from cattle,
sheep and pigs, CAP18 from rabbits and LL37 from humans; cationic
peptides enriched for specific amino acids, e.g.,
praline-containing peptides including abaecin from honeybees,
praline- and arginine-containing peptides including apidaecins from
honeybees, drosocin from Drosophila, pyrrhocoricin from European
sap-sucking bug, bactenicins from cattle (Bac7), sheep and goats
and PR-39 from pigs, praline- and phenylalanine-containing peptides
including prophenin from pigs, glycine-containing peptides
including hymenoptaecin from honeybees, glycine- and
praline-containing peptides including coleoptericin and holotricin
from beetles, tryptophan-containing peptides including indolicidin
from cattle, and small histidine-rich salivary polypeptides,
including histatins from humans and higher primates; anionic and
cationic peptides that contain cysteine and from disulfide bonds,
e.g., peptides with one disulphide bond including brevinins,
peptides with two disulfide bonds including alpha-defensins from
humans (HNP-1, HNP-2, cryptidins), rabbits (NP-1) and rats,
beta-defensins from humans (HBD1, DEFB118), cattle, mice, rats,
pigs, goats and poultry, and rhesus theta-defensin (RTD-1) from
rhesus monkey, insect defensins (defensin A); and anionic and
cationic peptide fragments of larger proteins, e.g., lactoferricin
from lactoferrin, casocidin 1 from human casein, and antimicrobial
domains from bovine alpha-lactalbumin, human hemoglobin, lysozyme,
and ovalbumin (see, e.g., Brogden, Nat. Rev. Microbiol. 3:238-250,
2005, which is incorporated herein by reference).
[0154] Further non-limiting examples of anti-microbial agents
include antibacterial drugs. Non-limiting examples of antibacterial
drugs include beta-lactam compounds, such as penicillin,
methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin,
ampicillin, ticarcillin, amoxicillin, carbenicillin, and
piperacillin; cephalosporins and cephamycins such as cefadroxil,
cefazolin, cephalexin, cephalothin, cephapirin, cephradine,
cefaclor, cefamandole, cefonicid, cefuroxime, cefprozil,
loracarbef, ceforanide, cefoxitin, cefmetazole, cefotetan,
cefoperazone, cefotaxime, ceftazidine, ceftizoxine, ceftriaxone,
cefixime, cefpodoxime, proxetil, cefdinir, cefditoren, pivoxil,
ceftibuten, moxalactam, and cefepime; other beta-lactam drugs such
as aztreonam, clavulanic acid, sulbactam, tazobactam, ertapenem,
imipenem, and meropenem; other cell wall membrane active agents
such as vancomycin, teicoplanin, daptomycin, fosfomycin,
bacitracin, and cycloserine; tetracyclines such as tetracycline,
chlortetracycline, oxytetracycline, demeclocycline, methacycline,
doxycycline, minocycline, and tigecycline; macrolides such as
erythromycin, clarithromycin, azithromycin, and telithromycin;
aminoglycosides such as streptomycin, neomycin, kanamycin,
amikacin, gentamicin, tobramycin, sisomicin, and netilmicin;
sulfonamides such as sulfacytine, sulfisoxazole, silfamethizole,
sulfadiazine, sulfamethoxazole, sulfapyridine, and sulfadoxine;
fluoroquinolones such as ciprofloxacin, enoxacin, gatifloxacin,
gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin,
norfloxacin, and ofloxacin; antimycobacteria drugs such as
isoniazid, rifampin, rifabutin, rifapentine, pyrazinamide,
ethambutol, ethionamide, capreomycin, clofazimine, and dapsone; and
miscellaneous antimicrobials such as colistimethate sodium,
methenamine hippurate, methenamine mandelate, metronidazole,
mupirocin, nitrofurantoin, polymyxin B, clindamycin,
choramphenicol, quinupristin-dalfopristin, linezolid,
spectinomycin, trimethoprim, pyrimethamine, and
trimethoprim-sulfamethoxazole.
[0155] Further non-limiting examples of anti-microbial agents
include antifungal agents. Non-limiting examples of antifungal
agents include anidulafungin, amphotericin B, butaconazole,
butenafine, caspofungin, clotrimazole, econazole, fluconazole,
flucytosine griseofulvin, itraconazole, ketoconazole, miconazole,
micafungin, naftifine, natamycin, nystatin, oxiconazole,
sulconazole, terbinafine, terconazole, tioconazole, tolnaftate,
and/or voriconazole.
[0156] In an embodiment, the anti-microbial agents include, but are
not limited to, oxidizing chemicals suitable to disrupt or destroy
cell membranes. For example, some oxidizing chemicals may withdraw
electrons from a cell membrane causing it to, for example, become
destabilized. Destroying the integrity of cell membranes of, for
example, a pathogen may lead to cell death.
[0157] Further non-limiting examples of anti-microbial agents
include antiseptics and disinfectants. Non-limiting examples of
antiseptics and disinfectants include acetic acid, acrisorcin,
aluminum acetate, alcohols (e.g., ethanol, isopropanol, benzyl
alcohol, phenylethyl alcohol), aldehydes (e.g., formaldehyde,
glutaraldehyde), benzoic acid, boric acid, butylparaben,
chlorhexidine gluconate, chlorine sodium hypochlorite,
hexachlorophene, iodine, povidone-iodine, phenols, oxidizing agents
(e.g., hydrogen peroxide), parabens (e.g., butylparaben,
ethylparaben, methylparaben, propylparaben), phenylmercuric
acetate, phenylmercuric nitrate, potassium permanganate, propylene
oxide, pyrithione zinc, and quaternary ammonium (e.g., benzalkonium
chloride, cetylpyridinum chloride, benzethonium chloride),
nitrofurazone, selenium sulfide, silver nitrate, and silver
sulfadiazine.
[0158] Non-limiting examples of carriers include any matrix that
allows for transport of, for example, a disinfecting agent across
any tissue, cell membranes, and the like of a biological subject,
or that is suitable for use in contacting a biological subject, or
that allows for controlled release formulations of the compositions
disclosed herein. Further non-limiting examples of carriers include
at least one of creams, liquids, lotions, emulsions, diluents,
fluid ointment bases, gels, organic and inorganic solvents,
degradable or non-degradable polymers, pastes, salves, vesicle, and
the like. Further non-limiting examples of carriers include cyclic
oligosaccharides, ethasomes, hydrogels, liposomes, micelle,
microspheres, nisomes, non-ionic surfactant vesicles, organogels,
phospholipid surfactant vesicles, phospholipid surfactant vesicles,
transfersomes, virosomes. Further non-limiting examples of
energy-sensitive carriers and the like include electrical
energy-sensitive, light sensitive, pH-sensitive, ion-sensitive,
sonic energy sensitive, ultrasonic energy sensitive carriers.
Further non-limiting examples of energy-sensitive carriers and the
like include cavitationally actuated drug delivery carriers,
acoustically actuated drug delivery carries, and the like
[0159] In an embodiment, the anti-microbial agent includes at least
one active agent that selectively targets bacteria. For example, in
an embodiment, the anti-microbial agent includes at least one
bacteriophage that, for example, selectively targets bacteria.
Bacteriophages generally comprise an outer protein hull enclosing
genetic material. The genetic material can be ssRNA, dsRNA, ssDNA,
or dsDNA. Bacteriophages are generally smaller than the bacteria
they destroy, and range from about 20 nm to about 200 nm.
Non-limiting examples of bacteriophages include T2, T4, T6,
phiX-174, MS2, and the like. In an embodiment, the bacteriophage
includes at least one engineered enzymatically active
bacteriophage. For example, particular enzymatically active
bacteriophage sets assist in dispersing biofilms. See U.S. Patent
App. Pub. No. 20090155215, which is incorporated herein by
reference.
[0160] Among antimicrobial agent compositions, examples include,
but are not limited to, diluted solutions of NaCl, hypochlorous
acid solutions (HAS), oxidative reduction potential aqueous
compositions, STERILOX TX (PuriCore Inc.), STERILOX Solutions
(PuriCore Inc.), MICROCYN (Nofil Corp.), superoxidized aqueous
compositions, superoxidized water, superoxide dismutase
compositions, physiologically balanced ionized acidic solutions,
and the like. Further non-limiting examples of antimicrobial agent
compositions may be found in, for example, the following documents
(the contents of which are incorporated herein by reference): U.S.
Pat. Nos. 7,276,255 (issued Oct. 2, 2007), 7,183,048 (issued Feb.
27, 2007), 6,506,416 (issued Jan. 14, 2003), 6,426,066 (issued Jul.
30, 2002), and 5,622,848 (Apr. 22, 1997); and U.S. Patent Nos.
2007/0196357 (published Aug. 23, 2007), 2007/0173755 (published
Jul. 26, 2007), and 2005/0142157 (published Jun. 30, 2005).
[0161] In an aspect, the type of anti-microbial agent delivered and
the spatial and temporal sequence of delivery is tailored to the
catheter for the presence and/or development of drug resistant
microorganisms. For example, the antibiotic nafcillin is a
preferred first line of defense against methicillin-sensitive
Staphylococcus aureus [MSSA]. Other antibiotics used to treat MSSA
include but are not limited to cefazolin, clindamycin, and/or
dicloxacillin. However, methicillin-resistant Staphylococcus aureus
[MRSA] no longer responds to nafcillin and may require treatment
with other anti-microbial agents, including among other things
vancomycin, telavancin (a synthetic derivative of vancomycin),
trimethoprim-sulfamethoxazole (for some strains of MRSA),
minocycline, linezolid, quinupristin/dalfopristin, daptomycin,
and/or tigecycline. See, e.g., Herchline, "Staphylococcal
Infections," eMedicine, updated Jan. 8, 2010, accessed May 24, 2010
(emedicine.medscape.com), the content of which is incorporated
herein by reference. In a recent study of 182 bacterial isolates
from ICU patients infected with coagulase-negative staphylococcus,
95% were resistant to penicillin, 86% were resistant to oxacillin,
48% were resistant to erythromycin, 42% were resistant to
clindamycin, 54% were resistant to gentamicin, 66% were resistant
to ciprofloxacin, and 0% were resistant to vancomycin. In this same
study, multiresistance was commonly seen: 21% of the isolates were
resistant to six tested antibiotics, 34% to at least five tested
antibiotics and 59% were resistant to at least four of the seven
tested antibiotics. See, e.g., Agvald-Ohman, et al., Crit. Care,
8:R42-R47, 2004, which is incorporated herein by reference.
[0162] In an embodiment, the anti-microbial agent delivered from
one or more anti-microbial regions or reservoirs includes at least
one D-amino acid. For example, it has been reported that a factor
including at least one of D-leucine, D-methionine, D-tyrosine, or
D-tryptophan is capable of breaking down biofilms, and is capable
of preventing biofilm formation. In particular, biofilm formation
by Staphylococcus aureus and Pseudomonas aeruginosa were inhibited.
See, for example, Kolodkin-Gal, et al., SCIENCE Vol. 328, pp.
627-629 (2010), which is incorporated herein by reference.
[0163] Among the one or more coatings, functionalized surfaces,
surface treatments, immuno-stimulating coatings, and the like,
examples include, among other things, polymeric compositions that
resist bacterial adhesion, antimicrobial coating, coatings that
controllably release antimicrobial agents, quaternary ammonium
silane coatings, chitosan coatings, and the like. Further
non-limiting examples of coatings, functionalized surfaces, surface
treatments, immuno-stimulating coatings, and the like may be found
in, for example, the following documents (the contents of which are
incorporated herein by reference): U.S. Pat. Nos. 7,348,021 (issued
Mar. 25, 2008), 7,217,425 (issued May 15, 2007), 7,151,139 (issued
Dec. 19, 2006), and 7,143,709 (issued Dec. 5, 2006). In an
embodiment, at least a portion of an inner or an outer surface of
the implantable device includes one or more self-cleaning coating
materials. Examples of self-cleaning coating (e.g., Lotus Effect)
materials include, but are not limited to titanium dioxide,
superhydrophobic materials, carbon nanotubes with nanoscopic
paraffin coating, or the like. Further non-limiting examples of
self-cleaning (e.g., non fouling) coating materials include
antimicrobial, and nonfouling zwitterionic polymers, zwitterionic
surface forming materials, zwitterionic polymers,
poly(carboxybetaine methacrylate) (pCBMA), poly(carboxybetaine
acrylic amide) (pCBAA), poly(oligo(ethylene glycol) methyl ether
methacrylate) (pOEGMA),
poly(N,N-dimethyl-N-(ethoxycarbonylmethyl)-N-[2'-(methacryloylo-
xy)ethyl]-ammonium bromide), cationic pC8NMA, switchable pCBMA-1
C2, pCBMA-2, and the like. See, e.g., WO 2008/083390 (published
Jul. 10, 2008) (the contents of which are incorporated herein by
reference).
[0164] In an embodiment, at least one of the inner surface or the
outer surface of the body structure includes at least one
high-aspect ratio polymer nanofibrillar structure (e.g., in the
form of stooped or crispated nanohairs). See, for example, Kim, et
al. Langmuir, vol. 25, no. 16, pp. 8879-8882 (2009), which is
incorporated herein by reference. In an embodiment, the
nanofibrillar surface can be controlled by oblique electron beam
irradiation, such that the geometry of polymer nanohairs is tunable
according to the tilting angle of the electron beam, the
acceleration voltage, and the exposure time. Id.
[0165] In an embodiment, at least one of the inner surface or the
outer surface of the body structure is switchable by exposure to
ultraviolet light. For example, a fluorinated diarylethene molecule
with two thiophene rings decorated with methoxy and methylated
silane pendant groups undergo reversible photoisomerization between
open and closed ring forms when irradiated with UV light. See,
Greene, Materials Today, vol. 9, no. 11, p. 15 (2006), which is
incorporated herein by reference.
[0166] In an embodiment, at least one of the inner surface or outer
surface of the body structure includes graphene film configured to
be superhydrophobic (contact angle of about 160 degrees) to
superhydrophilic (contact angle of about 0 degrees), by
manipulating the roughness of the surface.
[0167] In an embodiment, at least one anti-microbial region
includes at least one self-cleaning coating, or other coating. In
an embodiment, at least one anti-microbial region includes at least
one surface structure composition or deposition. In an embodiment,
the surface structure includes at least one substrate manufactured
to include nanoscale topographic anti-microbial features.
[0168] Further non-limiting examples of coatings include
superhydrophobic conducting polypyrrole films, coating, or
components that are electrically switchable between an oxidized
state and a neutral state, resulting in reversibly switchable
superhydrophobic and superhydrophilic properties (see, e.g., Lahann
et al., A Reversibly Switching Surface, 299 (5605): 371-374 (2003)
21:47-51 (2003), the contents of which are incorporated herein by
reference); coatings including electrically isolatable
fluid-support structures (see, e.g., U.S. Pat. No. 7,535,692
(issued May 19, 2009), the contents of which are incorporated
herein by reference); coatings including a plurality of
volume-tunable nanostructures (see, e.g., U.S. Patent Publication
No. 2008/0095977 (published Apr. 24, 2008), the contents of which
are incorporated herein by reference); coatings including
re-entrant surface structures (see, e.g., Tuteja et al., Robust
Omniphobic Surfaces, Epub 2008 Nov. 10, 105(47):18200-5 (2008), the
contents of which are incorporated herein by reference); coatings
including superhydrophobic conducting polypyrrole materials,
coatings including zwitterionic polymers (see, e.g., Cheng et al.,
A Switchable Biocompatible Polymer Surface with Self-Sterilizing
and Nonfouling Capabilities, Angew. Chem. Int. Ed. 8831-8834
(2008), the contents of which are incorporated herein by
reference); or the like.
[0169] Among active agents, examples include, but are not limited
to, adjuvants, allergens, analgesics, anesthetics, antibacterial
agents, antibiotics, antifungals, anti-inflammatory agents (e.g.,
nonsteroidal anti-inflammatory drugs), antimicrobials,
antioxidants, antipyretics, anti-tumor agents, antivirals,
bio-control agents, biologics or bio-therapeutics, chemotherapy
agents, disinfecting agents, energy-actuatable active agents,
immunogens, immunological adjuvants, immunological agents,
immuno-modulators, immuno-response agents, immuno-stimulators
(e.g., specific immuno-stimulators, non-specific
immuno-stimulators, or the like), immuno-suppressants,
non-pharmaceuticals (e.g., cosmetic substances, or the like),
pharmaceuticals, protease inhibitors or enzyme inhibitors, receptor
agonists, receptor antagonists, active agents, tolerogens,
toll-like receptor agonists, toll-like receptor antagonists,
vaccines, or combinations thereof.
[0170] Further non-limiting examples of active agents include
nonsteroidal anti-inflammatory drugs such as acemetacin, aclofenac,
aloxiprin, amtolmetin, aproxen, aspirin, azapropazone, benorilate,
benoxaprofen, benzydamine hydrochloride, benzydamine hydrochloride,
bromfenal, bufexamac, butibufen, carprofen, celecoxib, choline
salicylate, clonixin, desoxysulindac, diflunisal, dipyone,
droxicam, etodolac, etofenamate, etoricoxib, felbinac, fenbufen,
fenoprofen, fentiazac, fepradinol, floctafenine, flufenamic acid,
indomethacin, indoprofen, isoxicam, ketoralac, licofelone,
lomoxicam, loxoprofen, magnesium salicylate, meclofenamic acid,
meclofenamic acid, mefenamic acid, meloxicam, morniflumate,
niflumic acid, nimesulide, oxaprozen, phenylbutazone, piketoprofen,
piroxicam, pirprofen, priazolac, propyphenazone, proquazone,
rofecoxib, salalate, salicylamide, salicylic acid, sodium
salicylate, sodium thiosalicylate, sulindac, suprofen, tenidap,
tenoxicam, tiaprofenic acid, tolmetin, tramadol, trolamine
salicylate, zomepirac, or the like. Further non-limiting examples
of active agents include energy (e.g., chemical energy, electrical
resistance, laser energy, terahertz energy, microwave energy,
optical energy, radio frequency energy, sonic energy, thermal
energy, thermal resistance heating energy or ultrasonic energy, or
the like)-actuatable active agents, and the like.
[0171] In an embodiment, the active agent includes at least one
active agent that selectively targets bacteria. For example, in an
embodiment, the active agent includes at least one bacteriophage
that can, for example, selectively target bacteria. Bacteriophages
generally comprise an outer protein hull enclosing genetic
material. The genetic material can be ssRNA, dsRNA, ssDNA, or
dsDNA. Bacteriophages are generally smaller than the bacteria they
destroy generally ranging from about 20 nm to about 200 nm.
Non-limiting examples of bacteriophages include T2, T4, T6,
phiX-174, MS2, or the like). In an embodiment, the active agent
includes at least one energy-actuatable agent that selectively
targets bacteria. For example, in an embodiment, the active agent
includes at least one triplet excited-state photosensitizer that
can, for example, selectively target bacteria.
[0172] Further non-limiting examples of active agents include
triplet excited-state photosensitizers, reactive oxygen species,
reactive nitrogen species, any other inorganic or organic ion or
molecules that include oxygen ions, free radicals, peroxides, or
the like. Further non-limiting examples of active agents include
compounds, molecules, or treatments that elicit a biological
response from any biological subject. Further non-limiting examples
of disinfecting agents include active agents (e.g., antimicrobial
active agents), pharmaceuticals (e.g., a drug, a therapeutic
compound, pharmaceutical salts, or the like) non-pharmaceuticals
(e.g., a cosmetic substance, or the like), nutraceuticals,
antioxidants, phytochemicals, homeopathic agents, and the like.
Further non-limiting examples of disinfecting agents include
peroxidases (e.g., haloperoxidases such as chloroperoxidase, or the
like), oxidoreductase (e.g., myeloperoxidase, eosinophil
peroxidase, lactoperoxidase, or the like) oxidases, and the
like.
[0173] Further non-limiting examples of active agents include one
or more pore-forming toxins. Non limiting examples of pore-forming
toxins include beta-pore-forming toxins, e.g., hemolysin,
Panton-Valentine leukocidin S, aerolysin, Clostridial
epsilon-toxin; binary toxins, e.g., anthrax, C. perfringens lota
toxin, C. difficile cytolethal toxins; cholesterol-dependent
cytolysins; pneumolysin; small pore-forming toxins; and gramicidin
A.
[0174] Further non-limiting examples of active agents include one
or more pore-forming antimicrobial peptides. Antimicrobial peptides
represent an abundant and diverse group of molecules that are
naturally produced by many tissues and cell types in a variety of
invertebrate, plant and animal species. The amino acid composition,
amphipathicity, cationic charge and size of antimicrobial peptides
allow them to attach to and insert into microbial membrane bilayers
to form pores leading to cellular disruption and death. More than
800 different antimicrobial peptides have been identified or
predicted from nucleic acid sequences, a subset of which are
available in a public database (see, e.g., Wang & Wang, Nucleic
Acids Res. 32:D590-D592, 2004); http://aps.unmc.edu/AP/main.php,
which is incorporated herein by reference). More specific examples
of antimicrobial peptides include, but are not limited to, anionic
peptides, e.g., maximin H5 from amphibians, small anionic peptides
rich in glutamic and aspartic acids from sheep, cattle and humans,
and dermcidin from humans; linear cationic alpha-helical peptides,
e.g., cecropins (A), andropin, moricin, ceratotoxin, and melittin
from insects, cecropin P1 from Ascaris nematodes, magainin 2,
dermaseptin, bombinin, brevinin-1, esculentins and buforin II from
amphibians, pleurocidin from skin mucous secretions of the winter
flounder, seminalplasmin, BMAP, SMAP (SMAP29, ovispirin), PMAP from
cattle, sheep and pigs, CAP18 from rabbits and LL37 from humans;
cationic peptides enriched for specific amino acids, e.g.,
praline-containing peptides including abaecin from honeybees,
praline- and arginine-containing peptides including apidaecins from
honeybees, drosocin from Drosophila, pyrrhocoricin from European
sap-sucking bug, bactenicins from cattle (Bac7), sheep and goats
and PR-39 from pigs, praline- and phenylalanine-containing peptides
including prophenin from pigs, glycine-containing peptides
including hymenoptaecin from honeybees, glycine- and
praline-containing peptides including coleoptericin and holotricin
from beetles, tryptophan-containing peptides including indolicidin
from cattle, and small histidine-rich salivary polypeptides,
including histatins from humans and higher primates; anionic and
cationic peptides that contain cysteine and from disulfide bonds,
e.g., peptides with one disulphide bond including brevinins,
peptides with two disulfide bonds including alpha-defensins from
humans (HNP-1, HNP-2, cryptidins), rabbits (NP-1) and rats,
beta-defensins from humans (HBD1, DEFB118), cattle, mice, rats,
pigs, goats and poultry, and rhesus theta-defensin (RTD-1) from
rhesus monkey, insect defensins (defensin A); and anionic and
cationic peptide fragments of larger proteins, e.g., lactoferricin
from lactoferrin, casocidin 1 from human casein, and antimicrobial
domains from bovine alpha-lactalbumin, human hemoglobin, lysozyme,
and ovalbumin (see, e.g., Brogden, Nat. Rev. Microbiol. 3:238-250,
2005, which is incorporated herein by reference).
[0175] Further non-limiting examples of active agents include
antibacterial drugs. Non-limiting examples of antibacterial drugs
include beta-lactam compounds such as penicillin, methicillin,
nafcillin, oxacillin, cloxacillin, dicloxacillin, ampicillin,
ticarcillin, amoxicillin, carbenicillin, and piperacillin;
cephalosporins and cephamycins such as cefadroxil, cefazolin,
cephalexin, cephalothin, cephapirin, cephradine, cefaclor,
cefamandole, cefonicid, cefuroxime, cefprozil, loracarbef,
ceforanide, cefoxitin, cefmetazole, cefotetan, cefoperazone,
cefotaxime, ceftazidine, ceftizoxine, ceftriaxone, cefixime,
cefpodoxime, proxetil, cefdinir, cefditoren, pivoxil, ceftibuten,
moxalactam, and cefepime; other beta-lactam drugs such as
aztreonam, clavulanic acid, sulbactam, tazobactam, ertapenem,
imipenem, and meropenem; other cell wall membrane active agents
such as vancomycin, teicoplanin, daptomycin, fosfomycin,
bacitracin, and cycloserine; tetracyclines such as tetracycline,
chlortetracycline, oxytetracycline, demeclocycline, methacycline,
doxycycline, minocycline, and tigecycline; macrolides such as
erythromycin, clarithromycin, azithromycin, and telithromycin;
aminoglycosides such as streptomycin, neomycin, kanamycin,
amikacin, gentamicin, tobramycin, sisomicin, and netilmicin;
sulfonamides such as sulfacytine, sulfisoxazole, silfamethizole,
sulfadiazine, sulfamethoxazole, sulfapyridine, and sulfadoxine;
fluoroquinolones such as ciprofloxacin, gatifloxacin, gemifloxacin,
levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, and
ofloxacin; antimycobacteria drugs such as isoniazid, rifampin,
rifabutin, rifapentine, pyrazinamide, ethambutol, ethionamide,
capreomycin, clofazimine, and dapsone; and miscellaneous
antimicrobials such as colistimethate sodium, methenamine
hippurate, methenamine mandelate, metronidazole, mupirocin,
nitrofurantoin, polymyxin B, clindamycin, choramphenicol,
quinupristin-dalfopristin, linezolid, spectrinomycin, trimethoprim,
pyrimethamine, and trimethoprim-sulfamethoxazole.
[0176] Further non-limiting examples of active agents include
antifungal agents. Non-limiting examples of antifungal agents
include anidulafungin, amphotericin B, butaconazole, butenafine,
caspofungin, clotrimazole, econazole, fluconazole, flucytosine
griseofulvin, itraconazole, ketoconazole, miconazole, micafungin,
naftifine, natamycin, nystatin, oxiconazole, sulconazole,
terbinafine, terconazole, tioconazole, tolnaftate, and/or
voriconazole.
[0177] Further non-limiting examples of active agents include
anti-parasite agents. Non-limiting examples of anti-parasite agents
include antimalaria drugs such as chloroquine, amodiaquine,
quinine, quinidine, mefloquine, primaquine,
sulfadoxine-pyrimethamine, atovaquone-proguanil,
chlorproguanil-dapsone, proguanil, doxycycline, halofantrine,
lumefantrine, and artemisinins; treatments for amebiasis such as
metronidazole, iodoquinol, paromomycin, diloxanide furoate,
pentamidine, sodium stibogluconate, emetine, and dehydroemetine;
and other anti-parasite agents such as pentamidine, nitazoxanide,
suramin, melarsoprol, eflornithine, nifurtimox, clindamycin,
albendazole, and tinidazole. Further non-limiting examples of
active agents include ionic silver, (SilvaSorb.RTM., Medline
Industries, Inc), anti-microbial silver compositions (Arglaes.RTM.,
Medline Industries, Inc), or the like. Further non-limiting
examples of active agents include superoxide-forming compositions.
Further non-limiting examples of active agents include
oxazolidinones, gram-positive antibacterial agents, or the like.
See, e.g., U.S. Pat. No. 7,322,965 (issued Jan. 29, 2008), which is
incorporated herein by reference.
[0178] In an embodiment, the active agent includes one or more
antimicrobial agents. In an embodiment, the antimicrobial agent is
an antimicrobial peptide. Amino acid sequence information for a
subset of these can be found as part of a public database (see,
e.g., Wang & Wang, Nucleic Acids Res. 32:D590-D592, 2004);
http://aps.unmc.edu/AP/main.php, which is incorporated herein by
reference). Alternatively, a phage library of random peptides can
be used to screen for peptides with antimicrobial properties
against live bacteria, fungi and/or parasites. The DNA sequence
corresponding to an antimicrobial peptide can be generated ex vivo
using standard recombinant DNA and protein purification
techniques.
[0179] In an embodiment, one or more of the active agent include
chemicals suitable to disrupt or destroy cell membranes. For
example, some oxidizing chemicals can withdraw electrons from a
cell membrane causing it to, for example, become destabilized.
Destroying the integrity of cell membranes of, for example, a
pathogen can lead to cell death.
[0180] Non-limiting examples of energy-actuatable active agents
include radiation absorbers, light energy absorbers, X-ray
absorbers, photoactive agents, and the like. Non-limiting examples
of photoactive agents include, but are not limited to photoactive
antimicrobial agents (e.g., eudistomin, photoactive porphyrins,
photoactive TiO.sub.2, antibiotics, silver ions, antibodies, nitric
oxide, or the like), photoactive antibacterial agents, photoactive
antifungal agents, and the like. Further non-limiting examples of
energy-actuatable agent includes energy-actuatable disinfecting
agents, photoactive agents, or a metabolic precursor thereof. In an
embodiment, the at least one energy-actuatable agent includes at
least one X-ray absorber. In an embodiment, the at least one
energy-actuatable agent includes at least one radiation
absorber.
[0181] The at least one active agent reservoir can include, for
example, among other things an acceptable carrier. In an
embodiment, at least one active agent is carried by, encapsulated
in, or forms part of, an energy-sensitive (e.g.,
energy-actuatable), carrier, vehicle, vesicle, pharmaceutical
vehicle, pharmaceutical carrier, pharmaceutically acceptable
vehicle, pharmaceutically acceptable carrier, or the like.
[0182] Non-limiting examples of carriers include any matrix that
allows for transport of, for example, a disinfecting agent across
any tissue, cell membranes, and the like of a biological subject,
or that is suitable for use in contacting a biological subject, or
that allows for controlled release formulations of the compositions
disclosed herein. Further non-limiting examples of carriers include
at least one of creams, liquids, lotions, emulsions, diluents,
fluid ointment bases, gels, organic and inorganic solvents,
degradable or non-degradable polymers, pastes, salves, vesicle, and
the like. Further non-limiting examples of carriers include cyclic
oligosaccharides, ethasomes, hydrogels, liposomes, micelle,
microspheres, nisomes, non-ionic surfactant vesicles, organogels,
phospholipid surfactant vesicles, phospholipid surfactant vesicles,
transfersomes, virosomes. Further non-limiting examples of
energy-sensitive carriers and the like include electrical
energy-sensitive, light sensitive, pH-sensitive, ion-sensitive,
sonic energy sensitive, ultrasonic energy sensitive carriers.
[0183] In an embodiment, one or more active agents are carried by
energy-sensitive vesicles (e.g., energy-sensitive cyclic
oligosaccharides, ethasomes, hydrogels, liposomes, micelles,
microspheres, nisomes, non-ionic surfactant vesicles, organogels,
phospholipid surfactant vesicles, transfersomes, virosomes, and the
like.). In an embodiment, at least one of the one or more energy
emitters is configured to provide energy of a character and for a
time sufficient to liberate at least a portion of an active agent
carried by the energy-sensitive vesicles.
[0184] Among tracer agents, examples include one or more in vivo
clearance agents, magnetic resonance imaging agents, contrast
agents, dye-peptide compositions, fluorescent dyes, or tissue
specific imaging agents. In an embodiment, the one or more tracer
agents include at least one fluorescent dye. In an embodiment, the
one or more tracer agents include indocyanine green.
Formulations for Anti-Microbial Agents in Reservoirs
[0185] An anti-microbial agent delivered from one or more
anti-microbial agent reservoirs can be administered alone or in
combination with one or more pharmaceutically acceptable carriers,
diluents, excipients, and/or vehicles such as, for example,
buffers, surfactants, preservatives, solubilizing agents,
isotonicity agents, and stablilizing agents as appropriate. In an
embodiment, the anti-microbial agent can be carried by,
encapsulated in, or forms part of, an energy-sensitive (e.g.,
energy-actuatable), carrier, vehicle, vesicle, pharmaceutically
vehicle, pharmaceutically carrier, pharmaceutically acceptable
vehicle, pharmaceutically acceptable carrier, or the like. A
"pharmaceutically acceptable" carrier, for example, may be approved
by a regulatory agency of the state and/or Federal government such
as, for example, the United States Food and Drug Administration (US
FDA) or listed in the U.S. Pharmacopeia or other generally
recognized pharmacopeia for use in animals, and more particularly
in humans. Conventional formulation techniques generally known to
practitioners are described in Remington: The Science and Practice
of Pharmacy, 20.sup.th Edition, Lippincott Williams & White,
Baltimore, Md. (2000), which is incorporated herein by reference in
its entirety.
[0186] Acceptable pharmaceutical carriers include, but are not
limited to, the following: sugars, such as lactose, glucose and
sucrose; starches, such as corn starch and potato starch;
cellulose, and its derivatives, such as sodium carboxymethyl
cellulose, ethyl cellulose, cellulose acetate, and
hydroxymethylcellulose; polyvinylpyrrolidone; cyclodextrin and
amylose; powdered tragacanth; malt; gelatin, agar and pectin; talc;
oils, such as mineral oil, polyhydroxyethoxylated castor oil,
peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil,
corn oil and soybean oil; polysaccharides, such as alginic acid and
acacia; fatty acids and fatty acid derivatives, such as stearic
acid, magnesium and sodium stearate, fatty acid amines,
pentaerythritol fatty acid esters; and fatty acid monoglycerides
and diglycerides; glycols, such as propylene glycol; polyols, such
as glycerin, sorbitol, mannitol and polyethylene glycol; esters,
such as ethyl oleate and ethyl laurate; buffering agents, such as
magnesium hydroxide, aluminum hydroxide and sodium benzoate/benzoic
acid; water; isotonic saline; Ringer's solution; ethyl alcohol;
phosphate buffer solutions; other non-toxic compatible substances
employed in pharmaceutical compositions.
[0187] In an aspect, the anti-microbial agent is incorporated into
the anti-microbial agent reservoir in a liquid form and diffuses or
expels out of the reservoir once the release mechanism has been
triggered. The anti-microbial agent can be formulated in a
pharmaceutically acceptable liquid carrier. In an aspect, the
liquid carrier or vehicle is a solvent or liquid dispersion medium
comprising, for example, water, saline solution, ethanol, a polyol,
vegetable oils, nontoxic glyceryl esters, and suitable mixtures
thereof. The solubility of an anti-microbial agent can be enhanced
using solubility enhancers such as, for example, water; diols, such
as propylene glycol and glycerol; mono-alcohols, such as ethanol,
propanol, and higher alcohols; DMSO (dimethylsulfoxide);
dimethylformamide, N,N-dimethylacetamide; 2-pyrrolidone,
N-(2-hydroxyethyl)pyrrolidone, N-methylpyrrolidone,
1-dodecylazacycloheptan-2-one and other
n-substituted-alkyl-azacycloalkyl-2-ones and other
n-substituted-alkyl-azacycloalkyl-2-ones (azones). In some
instances, it may be preferable to include isotonic agents such as,
for example, sugars, buffers, sodium chloride or combinations
thereof.
[0188] In an aspect, the anti-microbial agent is incorporated into
the reservoir in a non-soluble form, either as one or more
dispersible particles or as an erodible form remaining in the
opened reservoir. For example, the anti-microbial agent can be
incorporated into the anti-microbial agent reservoir in solid form
and formulated to slowly dissolve in a time dependent manner once
in contact with the fluid environment of a patient's tissue. The
anti-microbial agent can be formulated in a slow release,
controlled release, or extended release biodegradable composition
that dissolves or breaks down in a time dependent manner. Examples
of slow release, controlled release, or extended release
compositions include but are not limited to hydrogels, polymers,
gelled and/or cross-linked water swellable polyolefins,
polycarbonates, polyesters, polyamides, polyethers, polyepoxides
and polyurethanes such as, for example, poly(acrylamide),
poly(2-hydroxyethyl acrylate), poly(2-hydroxypropyl acrylate),
poly(N-vinyl-2-pyrrolidone), poly(n-methylol acrylamide),
poly(diacetone acrylamide), poly(2-hydroxylethyl methacrylate),
poly(allyl alcohol). Other suitable polymers include but are not
limited to cellulose ethers, methyl cellulose ethers, cellulose and
hydroxylated cellulose, methyl cellulose and hydroxylated methyl
cellulose, gums such as guar, locust, karaya, xanthan gelatin, and
derivatives thereof.
[0189] As indicated in the Figures, in an embodiment, the device
includes at least one reservoir. In an embodiment, the reservoir
includes, but is not limited to, at least one of a metal, ceramic,
glass, non-crystalline material, semiconductor, composite, or
polymer. In an embodiment, the at least one reservoir includes at
least one active agent. In an embodiment, the at least one active
agent is in the form of a matrix including biodegradable material,
or biocompatible material. In certain instances, the release rate
of the at least one active agent can be regulated or controlled. In
an embodiment, the release rate of the at least one active agent is
continuous, for example, by diffusion out or through a material. In
an embodiment, the at least one reservoir includes at least one
biodegradable material. In an embodiment, degradation of the at
least one reservoir results in release of the contents of the at
least one reservoir, for example, by having at least a portion of
the at least one reservoir selectively degrade. In an embodiment,
the device includes multiple reservoirs. In an embodiment, one or
more of the multiple reservoirs are selectively degraded in order
to regulate release of the contests thereof.
[0190] One example of an active timed release device includes a
reservoir having a cap consisting of a thin film of conductive
material deposited over the reservoir and capable of dissolving or
disintegrating upon electrical conductivity. See, for example, U.S.
Patent App. Pub. No.: 20050149000, which is incorporated herein by
reference.
[0191] At least a portion of the devices and/or processes described
herein can be integrated into a data processing system. A data
processing system generally includes one or more of a system unit
housing, a video display device, memory such as volatile or
non-volatile memory, processors such as microprocessors or digital
signal processors, computational entities such as operating
systems, drivers, graphical user interfaces, and applications
programs, one or more interaction devices (e.g., a touch pad, a
touch screen, an antenna, etc.), and/or control systems including
feedback loops and control motors (e.g., feedback for detecting
position and/or velocity, control motors for moving and/or
adjusting components and/or quantities). A data processing system
can be implemented utilizing suitable commercially available
components, such as those typically found in data
computing/communication and/or network computing/communication
systems.
[0192] FIGS. 1A, 1B, 2A, and 2B show various embodiments of a
system 100 (e.g., a catheter system, an implantable catheter
system, an implantable system, an indwelling system, a partially
implantable system, a fluid management system, or the like
including an insertable device, partially implantable device, or
implantable device) in which one or more methodologies or
technologies can be implemented, such as, managing a transport of
fluids, providing surgical access, delivering therapeutics, as well
as actively detecting, treating, or preventing an infection (e.g.,
an implant-associated infection, a hematogenous associated
infection, an infection present in tissue or biological fluid, a
biofilm formation, a microbial colonization, or the like), a
biological sample abnormality (e.g., a cerebral spinal fluid
abnormality, a hematological abnormality, a tissue abnormality, or
the like), or the like. In an embodiment, the system 100 has at
least one component at least partially inserted into a biological
subject 222.
[0193] In an embodiment, the system 100 is configured to, among
other things, reduce an in vivo concentration of an infectious
agent (e.g., microorganism) present in a biological fluid (e.g.,
bodily fluid, blood, amniotic fluid, ascites, bile, cerebrospinal
fluid, interstitial fluid, pleural fluid, transcellular fluid, or
the like) managed by the system 100, or a biological sample 808
proximate one or more components of the system 100. In an
embodiment, the system 100 is configured to provide antimicrobial
therapy.
[0194] The system 100 can include, among other things, at least one
insertable device 102. In an embodiment, the insertable device 102
includes, among other things, a body structure 104 having an outer
surface 106 and an inner surface 108 defining one or more
fluid-flow passageways 110. In an embodiment, the system 100 is
configured to reduce the concentration of an infectious agent in
the immediate vicinity of an insertable device 102. For example, in
an embodiment, the system 100 is configured to controllably deliver
one or more anti-microbial agents to at least one of an inner
surface 108 or an outer surface 106 of one or more fluid-flow
passageways 110 of an insertable device 102.
[0195] The insertable device 102 can include, among other things,
one or more catheters 112. In an embodiment, the insertable device
102 is positioned to facilitate the administration of therapeutics
(e.g., anti-microbial agents or other therapeutic agents),
nutraceuticals, intravenous fluids, blood products, parenteral
nutrition, or the like. In an embodiment, the insertable device 102
is positioned to provide access for surgical instruments. In an
embodiment, the insertable device 102 is positioned to provide
vascular access. In an embodiment, the insertable device 102 is
positioned to facilitate drainage.
[0196] Among catheters 112, examples include, but are not limited
to, arterial catheters, dialysis catheters, drainage catheters,
indwelling catheters, long term non-tunneled central venous
catheters, long term tunneled central venous catheters, mechanical
catheters, peripheral venous catheters, peripherally insertable
central venous catheters, peritoneal catheters, pulmonary artery
Swan-Ganz catheters, short-term central venous catheters, urinary
catheters, ventricular catheters, and the like. In an embodiment,
the body structure 104 includes one or more catheters 112 each
having a proximal portion 114, a distal portion 116, and at least
one fluid-flow passageway 110 extending therethrough. In an
embodiment, one or more of the catheters 112 are configured for
insertion into a body cavity, a duct, or a vessel of a subject. In
an embodiment, the system 100 can include, among other things, one
or more power sources 900.
[0197] In an embodiment, at least one of the anti-microbial regions
202 is selectively actuatable 202a. In an embodiment, at least one
of the anti-microbial regions 202 is selectively actuatable between
at least a first actuatable state and a second actuatable state. In
an embodiment, at least one of the anti-microbial regions 202 is
independently addressable 202b. In an embodiment, the insertable
device 102 includes one or more ports 118 configured to provide
access to, or from, an interior environment of at least one of the
fluid-flow passageways 110.
[0198] In an embodiment, at least one of the anti-microbial regions
202 is configured to provide at least one anti-microbial property
204 of a character and for a time sufficient to inhibit microbial
growth or microbial adherence to at least one of the anti-microbial
regions 202 of the body structure 104. In an embodiment, at least
one of the anti-microbial regions 202 is configured to provide at
least one anti-microbial property 204 of a character and for a time
sufficient to inhibit at least one of microbial aggregation on the
surface of the body structure 104. In an embodiment, at least one
of the anti-microbial regions 202 is configured to provide at least
one anti-microbial property 204 of a character and for a time
sufficient to inhibit adherence of at least one extracellular
matrix component to the surface of the body structure 104. In an
embodiment, the extracellular matrix component includes at least
one of a protein, or glycosaminoglycan. In an embodiment, the at
least one anti-microbial property 204 includes at least one of
nano-scale or micro-scale roughness.
[0199] In an embodiment, the anti-microbial agent includes at least
one of an anti-fungal agent, anti-parasitic agent, energy emitter,
photoactive material, thermal plasmonic structure, thermal ridge,
nanostructure, microstructure, surface undulation, protease, amino
acid, surfactant, electricity, optical energy, plasmonic energy,
bacteriophage, photoactive material, or antibiotic. In an
embodiment, the bacteriophage includes an engineered enzymatically
active bacteriophage. In an embodiment, the anti-microbial agent
includes at least two different bacteriophage sets.
[0200] In an embodiment, the antibiotic includes at least one of
azithromycin, clarithromycin, clindamycin, dirithromycin,
erythromycin, lincomycin, troleandomycin, cinoxacin, ciprofloxacin,
enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin,
moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin,
trovafloxacin, oxolinic acid, gemifloxacin, perfloxacin,
imipenem-cilastatin, meropenem, aztreonam, amikacin, gentamicin,
kanamycin, neomycin, netilmicin, streptomycin, tobramycin,
paromomycin, teicoplanin, vancomycin, demeclocycline, doxycycline,
methacycline, minocycline, oxytetracycline, tetracycline,
chlortetracycline, mafenide, sulfadizine, sulfacetamide,
sulfadiazine, sulfamethoxazole, sulfasalazine, sulfisoxazole,
trimethoprim-sulfamethoxazole, sulfamethizole, linezolid,
quinopristin+dalfopristin, bacitracin, chloramphenicol,
colistemetate, fosfomycin, isoniazid, methenamine, metronidazol,
mupirocin, nitrofurantoin, nitrofurazone, novobiocin, polymyxin B,
spectinomycin, trimethoprim, coliistin, cycloserine, capreomycin,
ethionamide, pyrazinamide, para-aminosalicyclic acid, erythromycin
ethylsuccinate+sulfisoxazole, penicillin, beta-lactamase inhibitor,
methicillin, cefaclor, cefamandole nafate, cefazolin, cefixime,
cefinetazole, cefonioid, cefoperazone, ceforanide, cefotanme,
cefotaxime, cefotetan, cefoxitin, cefpodoxime proxetil,
ceftazidime, ceftizoxime, ceftriaxone, cefriaxone moxalactam,
cefuroxime, cephalexin, cephalosporin C, cephalosporin C sodium
salt, cephalothin, cephalothin sodium salt, cephapirin, cephradine,
cefuroximeaxetil, dihydratecephalothin, moxalactam, loracarbef
mafate, Amphotericin B, Carbol-Fuchsin, Ciclopirox, Clotrimzole,
Econazole, Haloprogin, Ketoconazole, Mafenide, Miconazole,
Naftifine, Nystatin, Oxiconazole Silver, Sulfadiazine, Sulconazole,
Terbinatine, Tioconazole, Tolnaftate, Undecylenic acid,
flucytosine, miconazole, cephabam, beta-lactam, or cephalosporin.
In an embodiment, the anti-microbial agent includes at least one of
a macrolide, lincosamine, quinolone, fluoroquinolone, carbepenem,
monobactam, aminoglycoside, glycopeptide, enzyme, tetracycline,
sulfonamide, rifampin, oxazolidonone, streptogramin, or a synthetic
moiety thereof. In an embodiment, the anti-microbial agent includes
at least one surfactant or amino acid. In an embodiment, the amino
acid includes at least one D-amino acid. In an embodiment, the
anti-microbial agent includes at least one of a ceramic,
super-oxide forming compound, enzyme, or polymer. In an embodiment,
the anti-microbial agent includes at least one metal, or salt
thereof. In an embodiment, the enzyme includes at least one of
DNAse, protease, glucosidase, or endopeptidase. In an embodiment,
the ceramic includes zeolite, optionally with silver ions exchanged
onto internal acidic sites of the zeolite. In an embodiment, the
anti-microbial agent includes polytetrafluoroethylene. In an
embodiment, the anti-microbial agent includes at least one of Group
B Streptococci phage lysin, aminoglycoside, carbapenem,
cephlasporin, fluoroquinolone, glycylcycline, macrolide,
monobactam, penicillin, polypeptide, sulfonamide, tetracycline,
metronidazole, rifampin, pyrazinamide, nitrofurantoin,
quinupristin-dalfopristin, spectinomycin, telithromycin,
vancomycin, linezolid, isoniazid, fosfomycin, ethambutol,
daptomycin, clindamycin, or chloramphenicol. In an embodiment at
least one of the anti-microbial regions 202 includes at least one
of silver, copper, zirconium, diamond, rubidium, platinum, gold,
nickel, lead, cobalt, potassium, zinc, bismuth, tin, cadmium,
chromium, aluminum, calcium, mercury, thallium, gallium, strontium,
barium, lithium, magnesium, oxides, hydroxides, or salts
thereof.
[0201] In an embodiment, an insertable device 102 includes a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; one or more
anti-microbial regions 202 including at least one D-amino acid
coating on at least one of the outer surface 106, inner surface
108, or embedded in the body structure 104. In an embodiment, the
D-amino acid includes at least one of D-leucine, D-methionine,
D-tyrosine, or D-tryptophan. In an embodiment, an insertable device
102 includes a body structure 104 having an outer surface 106 and
an inner surface 108 defining one or more fluid-flow passageways
110; one or more selectively actuatable anti-microbial regions 202a
including at least one anti-microbial reservoir 208 including at
least one D-amino acid, the anti-microbial reservoir 208 configured
to deliver at least one D-amino acid to at least one of the outer
surface 106 inner surface 108, or internal body structure 104.
[0202] In an embodiment, at least one of the anti-microbial regions
202 includes at least one of black silica, or hydrogenated diamond.
In an embodiment, at least one of the anti-microbial regions
includes at least one electroactive polymer. In an embodiment, at
least one of the anti-microbial regions includes at least one of
polyvinyl chloride, polyester, polyethylene, polypropylene,
ethylene, or polyolefin; or homopolymers or copolymers thereof.
[0203] In an embodiment, at least one of the anti-microbial regions
202 includes an anti-microbial property 204 selective for at least
one of a single phylum of microorganism, single genus of
microorganism, single strain of microorganism, or single
microorganism. In an embodiment, the at least one anti-microbial
property 204 is selected based on expected microorganism presence
or actual microorganism presence proximate the body structure 104.
In an embodiment, at least one anti-microbial property 204 is
selected based on expected microorganism response to at least one
other anti-microbial region 202 of the body structure 104.
[0204] In an embodiment, the body structure 104 of the insertable
device 102 includes at least one porous material 209. In an
embodiment, at least one of the anti-microbial regions 202 includes
at least one porous material 209. In an embodiment, the at least
one porous material 209 is configured to capture at least one
microorganism proximate to at least one of the inner surface 108 or
the outer surface 106 of the body structure 104. In an embodiment,
the at least one porous material 209 is further configured to
retain a captured microorganism. In an embodiment, the porous
material 209 includes hydrophobic polycations bound thereto. In an
embodiment, the hydrophobic polycations are covalently bound to the
porous material 209. In an embodiment, the hydrophobic polycations
include at least one of N-alkylated poly14-vinylpyridine,
hexyl-poly14-vinylpyridine, or N-hexylated-methylated high
molecular weight polyethylenimine. In an embodiment, the porous
material 209 includes at least one of cotton, wool, nylon, or
polyester.
[0205] In an embodiment, the insertable device 102 includes one or
more catheters 112 configured for directly detecting or monitoring
mechanical, physical, or biochemical functions associated with a
biological subject; draining or collecting body fluids; providing
access to an interior of a biological subject; or distending at
least one fluid-flow passageway 110; as well as for administering
therapeutics, nutraceuticals, intravenous fluids, nutrition, or the
like. In an embodiment, the insertable device 102 includes one or
more at least partially implantable catheters 112. In an
embodiment, the insertable device 102 includes one or more ports
118 configured to provide access to, or from, an interior
environment of at least one of the fluid-flow passageways 110. In
an embodiment, the insertable device 102 includes one or more
biocompatible materials, biodegradable materials, polymeric
materials, thermoplastics, silicone materials (e.g.,
polydimethysiloxanes), polyvinyl chloride materials, silk,
biodegradable polymer, hydrogel, latex rubber materials, or the
like.
[0206] In an embodiment, an at least partially implantable fluid
management system includes: a catheter assembly having a body
structure 104 including at least an outer surface 106 and an inner
surface 108 defining one or more fluid-flow passageways 110; and a
plurality of selectively actuatable anti-microbial regions 202a
configured to deliver at least one anti-microbial agent to at least
a portion of one or more of the outer surface 106, the inner
surface 108, or embedded in the internal body structure 104.
[0207] Further non-limiting examples of catheters 112, shunts,
medical ports, insertable devices, implantable devices, implantable
or insertable device assemblies, or components thereof, may be
found in, for example the following documents (the contents of each
of which is incorporated herein by reference): U.S. Pat. Nos.
7,524,298 (issued Apr. 28, 2009), 7,390,310 (issued Jun. 24, 2008),
7,334,594 (issued Feb. 26, 2008), 7,309,330 (issued Dec. 18, 2007),
7,226,441 (issued Jun. 5, 2007), 7,118,548 (issued Oct. 10, 2006),
6,932,787 (issued Aug. 23, 2005), 6,913,589 (issued Jul. 5, 2005),
6,743,190 (issued Jun. 1, 2004), 6,585,677 (issued Jul. 1, 2003);
and U.S. Patent Publication Nos. 2009/0118661 (published May 7,
2009), 2009/0054824 (published Feb. 26, 2009), 2009/0054827
(published Feb. 26, 2009), 2008/0039768 (published Feb. 14, 2008),
and 2006/0004317 (published Jan. 5, 2006).
[0208] In an embodiment, the one or more anti-microbial regions 202
can take a variety of shapes, configurations, or geometries,
including, but not limited to, cylindrical, conical, planar,
parabolic, regular or irregular forms. In an embodiment, a
plurality of anti-microbial regions 202 are configured as bands on
at least one of the outer surface 106, the inner surface 108, or
embedded in the body structure 104 of the device 102. The one or
more anti-microbial regions 202 can also form a variety of patterns
109 (e.g., spatial or temporal patterns), such as, repeating
pattern, non-repeating pattern, graduating pattern, blocking
pattern, or partially repeating pattern. In an embodiment, the at
least one spatial pattern or temporal pattern is derived from
information relating to the type of microorganism expected to be
present proximate the body structure 104. In an embodiment, the at
least one spatial pattern or temporal pattern is based at least in
part on information relating to at least one of the type of
microorganism previously detected on at least one anti-microbial
region of the body structure 104. In an embodiment, the blocking
pattern is configured such that it forms the sole pathway to
another pattern on the body structure 104. In an embodiment,
multiple anti-microbial regions 202 are formed from a single
substrate or structure. Non-limiting examples of anti-microbial
regions 202 include at least one anti-microbial surface property
204 (e.g., anti-microbial protruding elements 206 (e.g.,
anti-microbial nanostructures 206a, etc.), anti-microbial polymers,
anti-microbial metals, anti-microbial agents, etc., anti-microbial
reservoir 208 including at least one anti-microbial agent, or the
like). In an embodiment, the one or more anti-microbial regions 202
include at least one structure, agent, or other anti-microbial
surface property 204 suitable for directing at least one
microorganism toward or away from a particular location of the
insertable device 102. In an embodiment, the anti-microbial agent
is formulated to be released or activated over time.
[0209] In an embodiment, at least one of the anti-microbial regions
202 is actuatable 202a. In an embodiment, the actuatable
anti-microbial region 202a is configured to release at least one
anti-microbial agent based at least in part on at least one
detected microbial component associated with the biological sample
808. In an embodiment, at least one of the anti-microbial regions
202 is actuatable by the presence of at least one microorganism
(e.g., bacteria, fungi, etc.). In an embodiment, the at least one
microorganism includes at least one of Staphylococcus, Pseudomonas,
or Escherichia bacteria. In an embodiment, the at least one
microorganism includes at least one of Candida, or
Saccharomyces.
[0210] In an embodiment, the actuatable anti-microbial region 202a
is configured for reversible activation. In an embodiment, the at
least one actuatable anti-microbial region 202a is configured for
irreversible activation. In an embodiment, the actuatable
anti-microbial region 202a is actuatable by at least partial
degradation of the body structure 104.
[0211] In an embodiment, the insertable device 102 further
comprises at least one light source 211. In an embodiment, the at
least one light source 211 is coupled to at least one
anti-microbial region 202. In an embodiment, the at least one light
source 211 includes at least one of a light-emitting diode,
ultraviolet light source, or infrared light source.
[0212] In an embodiment, the system 100 comprises a body structure
104 having an outer surface 106 and an inner surface 108 defining
one or more fluid-flow passageways 110; at least one independently
addressable and actively controllable anti-microbial nanostructure
206a projecting from at least one of the outer surface 106, or the
inner surface 108 of the body structure 104; at least one sensor
302 configured to detect one or more microorganisms present
proximate the body structure 104; and means for determining the
presence of at least one microorganism proximate at least one of
the independently addressable and actively controllable
anti-microbial nanostructure 206a of the body structure 104. In an
embodiment, the system 100 further includes one or more
instructions for determining the presence of at least one
microorganism proximate at least one of the independently
addressable anti-microbial regions 202b of the body structure
104.
[0213] Referring to FIGS. 2A and 2B, the system 100 can include,
among other things, at least one sensor 302. In an embodiment, the
sensor 302 includes at least one of a plasmon sensor, pH sensor,
temperature sensor, piezoelectric sensor, electrostrictive sensor,
magnetostrictive sensor, biochemical sensor, optical sensor,
optical density sensor, refractive index sensor, biomass sensor,
electrochemical sensor, fluid-flow sensor, or electronic
sensor.
[0214] In an embodiment, the sensor 302 is configured to detect
(e.g., assess, calculate, evaluate, determine, gauge, measure,
monitor, quantify, resolve, sense, or the like) at least one
characteristic (e.g., a spectral characteristic, a spectral
signature, a physical quantity, a relative quantity, an
environmental attribute, a physiologic characteristic, or the like)
associated with a biological subject 222. In an embodiment, the
sensor 302 is configured to detect (e.g., assess, calculate,
evaluate, determine, gauge, measure, monitor, quantify, resolve,
sense, or the like) at least one characteristic (e.g., a spectral
characteristic, a spectral signature, a physical quantity, a
relative quantity, an environmental attribute, a physiologic
characteristic, or the like) a microbial component. In an
embodiment, the microbial component includes at least one a lipid,
peptide, lipopolysaccharide, flagellin, lipoteichoic acid,
peptidoglycan, nucleic acid (e.g., DNA, double stranded RNA, etc),
unmethylated CpG motifs, polypeptide, protein, glycolipid,
proteoglycan, lipoprotein, glycoprotein, glycosaminoglycan,
polysaccharide, glycopeptides, metalloprotein, enzyme,
carbohydrate, cytokine, microbial cell membrane, microbial cell
receptor, pathogen-associated molecular pattern, or other microbial
component.
[0215] In an embodiment, the sensor 302 is configured to detect
(e.g., assess, calculate, evaluate, determine, gauge, measure,
monitor, quantify, resolve, sense, or the like) at least one
characteristic (e.g., a spectral characteristic, a spectral
signature, a physical quantity, a relative quantity, an
environmental attribute, a physiologic characteristic, or the like)
of a microbial component proximate the body structure 104. In an
embodiment, the sensor 302 is configured to detect (e.g., assess,
calculate, evaluate, determine, gauge, measure, monitor, quantify,
resolve, sense, or the like) at least one characteristic (e.g., a
spectral characteristic, a spectral signature, a physical quantity,
a relative quantity, an environmental attribute, a physiologic
characteristic, or the like) of the presence of at least one
microorganism within at least one of the fluid-flow passageways
110. In an embodiment, the sensor 302 is configured to detect
(e.g., assess, calculate, evaluate, determine, gauge, measure,
monitor, quantify, resolve, sense, or the like) at least one
characteristic (e.g., a spectral characteristic, a spectral
signature, a physical quantity, a relative quantity, an
environmental attribute, a physiologic characteristic, or the like)
the presence of at least one microorganism proximate at least one
of the anti-microbial regions 202. In an embodiment, the sensor 302
is configured to detect (e.g., assess, calculate, evaluate,
determine, gauge, measure, monitor, quantify, resolve, sense, or
the like) at least one characteristic (e.g., a spectral
characteristic, a spectral signature, a physical quantity, a
relative quantity, an environmental attribute, a physiologic
characteristic, or the like) the presence of at least one
microorganism proximate one or more fluid-flow passageways 110. In
an embodiment, the sensor 302 is configured to detect (e.g.,
assess, calculate, evaluate, determine, gauge, measure, monitor,
quantify, resolve, sense, or the like) at least one characteristic
(e.g., a spectral characteristic, a spectral signature, a physical
quantity, a relative quantity, an environmental attribute, a
physiologic characteristic, or the like) of the presence of at
least one microorganism within the one or more fluid-flow
passageways 110 based on one or more flow characteristics.
[0216] In an embodiment, the sensor 302 is configured to perform a
real-time comparison of a measurand associated with a biological
sample 808 proximate the insertable device 102 to stored reference
data and to generate a response 299 based on the comparison. In an
embodiment, the sensor 302 is configured to perform a comparison of
a real-time detection associated with at least one anti-microbial
region 202 of at least one of the outer surface 106, or the inner
surface 108 of the body structure 104, to the microbial marker
information and to generate a response 299 based at least in part
on the comparison. In an embodiment, the sensor 302 is configured
to perform a comparison of a cumulative detection associated with
at least one anti-microbial region 202 of at least one of the outer
surface 106 or the inner surface 108 of the body structure 104 to
the microbial marker information to generate a response 299 based
at least in part on the comparison. For example, the response 299
can include, among other things, activating an authorization
protocol, activating an authentication protocol, activating a
software update protocol 333, activating a data transfer protocol
303, or activating an anti-microbial region diagnostic protocol
334. In an embodiment, the response 299 includes one or more of a
response 299 signal, control signal, or change in delivery of at
least one anti-microbial agent. In an embodiment, the response 299
includes one or more of sending information associated with at
least one of an authentication protocol, an authorization protocol,
an anti-microbial delivery protocol, an activation protocol, an
encryption protocol, or a decryption protocol.
[0217] In an embodiment, the sensor 302 is operably coupled to one
or more computing devices 230. In an embodiment, at least one
computing device 230 is operably coupled to the sensor 302 and
configured to process an output associated with one or more sensor
measurands. In an embodiment, at least one computing device 230 is
configured to concurrently or sequentially operate multiple sensors
302. In an embodiment, the sensor 302 includes a computing device
230 configured to process sensor measurand information and
configured to cause the storing of the measurand information in a
data storage medium. In an embodiment, the sensor 302 includes an
identification code and is configured to implement instructions
addressed to the sensor 302 according to the component
identification code.
[0218] In an embodiment, the sensor 302 includes one or more
surface plasmon resonance sensors. For example, in an embodiment,
the sensor 302 includes one or more localized surface plasmon
resonance sensors. In an embodiment, the sensor 302 includes a
light transmissive support and a reflective metal layer. In an
embodiment, the sensor 302 includes a wavelength-tunable surface
plasmon resonance sensor. In an embodimeht, the sensor 302 includes
a surface plasmon resonance microarray sensor having a
wavelength-tunable metal-coated grating. In an embodiment, the
sensor 302 includes a surface plasmon resonance microarray sensor
having an array of micro-regions configured to capture target
molecules.
[0219] In an embodiment, the sensor 302 includes one or more
electrochemical transducers, optical transducers, piezoelectric
transducers, or thermal transducers. For example, in an embodiment,
the sensor 302 includes one or more transducers configured to
detect acoustic waves associated with changes in a biological mass
present proximate a surface of the body structure 104.
[0220] In an embodiment, the sensor 302 includes one or more
thermal detectors, photovoltaic detectors, or photomultiplier
detectors. In an embodiment, the sensor 302 includes one or more
charge-coupled devices, complementary metal-oxide-semiconductor
devices, photodiode image sensor devices, whispering gallery mode
(WGM) micro cavity devices, photoelectric device,
wavelength-tunable surface plasmon resonance sensor, surface
plasmon resonance microarray sensor having a wavelength-tunable
metal-coating grating, or scintillation detector devices. In an
embodiment, the sensor 302 includes one or more ultrasonic
transducers.
[0221] In an embodiment, the sensor 302 includes at least one of an
imaging spectrometer, a photo-acoustic imaging spectrometer, a
thermo-acoustic imaging spectrometer, and a
photo-acoustic/thermo-acoustic tomographic imaging spectrometer. In
an embodiment, the sensor 302 includes at least one of a thermal
detector, a photovoltaic detector, or a photomultiplier
detector.
[0222] In an embodiment, the sensor 302 includes one or more
density sensors. In an embodiment, the sensor 302 includes one or
more optical density sensors. In an embodiment, the sensor 302
includes one or more refractive index sensors. In an embodiment,
the sensor 302 includes one or more fiber optic refractive index
sensors.
[0223] In an embodiment, the sensor 302 includes one or more
biosensors 303 (e.g., acoustic biosensors, amperometric biosensors,
calorimetric biosensors, optical biosensors, or potentiometric
biosensors). In an embodiment, the sensor 302 includes one or more
fluid-flow sensors. In an embodiment, the sensor 302 includes one
or more differential electrodes, biomass sensors, immunosensors, or
the like. In an embodiment, the sensor 302 includes one or more
one-, two-, or three-dimensional photodiode arrays.
[0224] In an embodiment, the system 100 includes one or more
sensors 302. In an embodiment, the insertable device 102 includes
one or more of the sensors 302. Non-limiting examples of sensors
302 include acoustic wave sensors, aptamer-based sensors,
biosensors, blood volume pulse sensors, cantilevers, conductance
sensors, fluorescence sensors, force sensors, heat sensors (e.g.,
thermistors, thermocouples, or the like), high resolution
temperature sensors, differential calorimeter sensors, optical
sensors, goniometry sensors, potentiometer sensors, resistance
sensors, respiration sensors, sound sensors (e.g., ultrasound),
Surface Plasmon Band Gap sensor (SPRBG), physiological sensors, and
the like. Further non-limiting examples of sensors 302 include
affinity sensors, bioprobes, biostatistics sensors, enzymatic
sensors, in-situ sensors (e.g., in-situ chemical sensor), ion
sensors, light sensors (e.g., visible, infrared, or the like),
microbiological sensors, microhotplate sensors, micron-scale
moisture sensors, nanosensors, optical chemical sensors, single
particle sensors, and the like.
[0225] Further non-limiting examples of sensors 302 include
chemical sensors, cavitand-based supramolecular sensors, nucleic
acid sensors, deoxyribonucleic acid sensors (e.g., electrochemical
DNA sensors, or the like), supramolecular sensors, and the like. In
an embodiment, at least one of the sensors 302 is configured to
detect or measure the presence or concentration of specific target
chemicals (e.g., blood components, biological sample component,
cerebral spinal fluid component, infectious agents, infection
indication chemicals, inflammation indication chemicals, diseased
tissue indication chemicals, biological agents, molecules, ions, or
the like).
[0226] Further non-limiting examples of sensors 302 include
chemical transducers, ion sensitive field effect transistors
(ISFETs), ISFET pH sensors, membrane-ISFET devices (MEMFET),
microelectronic ion-sensitive devices, potentiometric ion sensors,
quadruple-function ChemFET (chemical-sensitive field-effect
transistor) integrated-circuit sensors, sensors with
ion-sensitivity and selectivity to different ionic species, and the
like. Further non-limiting examples of the one or more sensors 302
can be found in the following documents (the contents of each of
which is incorporated herein by reference): U.S. Pat. Nos.
7,396,676 (issued Jul. 8, 2008) and 6,831,748 (issued Dec. 14,
2004).
[0227] In an embodiment, the one or more sensors 302 include one or
more acoustic transducers, electrochemical transducers,
photochemical transducer, optical transducers, piezoelectrical
transducers, or thermal transducers. For example, in an embodiment,
the one or more sensors 302 include one or more acoustic
transducers. In an embodiment, the one or more sensors 302 include
one or more thermal detectors, photovoltaic detectors, or
photomultiplier detectors. In an embodiment, the one or more
sensors 302 include one or more charge coupled devices,
complementary metal-oxide-semiconductor devices, photodiode image
sensor devices, whispering gallery mode micro cavity devices, or
scintillation detector devices. In an embodiment, the one or more
sensors 302 include one or more complementary
metal-oxide-semiconductor image sensors.
[0228] In an embodiment, the one or more sensors 302 include one or
more conductivity sensor. In an embodiment, the one or more sensors
302 include one or more spectrometers. In an embodiment, the one or
more sensors include one or more Bayer sensors. In an embodiment,
the one or more sensors include one or more Foveon sensors. In an
embodiment, the one or more sensors 302 include one or more density
sensors. In an embodiment, the one or more density sensors include
one or more optical density sensors. In an embodiment, the one or
more density sensors include one or more refractive index sensors.
In an embodiment, the one or more refractive index sensors include
one or more fiber optic refractive index sensors.
[0229] In an embodiment, the one or more sensors 302 include one or
more surface plasmon resonance sensors. In an embodiment, the one
or more sensors 302 are configured to detect target molecules. For
example, surface-plasmon-resonance-based-sensors detect target
molecules suspended in a fluid, for example, by reflecting light
off thin metal films in contact with the fluid. Adsorbing molecules
cause changes in the local index of refraction, resulting in
changes in the resonance conditions of the surface plasmon
waves.
[0230] In an embodiment, the one or more sensors 302 include one or
more localized surface plasmon resonance sensors. In an embodiment,
detection of target molecules includes monitoring shifts in the
resonance conditions of the surface plasmon waves due to changes in
the local index of refraction associates with adsorption of target
molecules. In an embodiment, the one or more sensors 302 include
one or more functionalized cantilevers. In an embodiment, the one
or more sensors 302 include a light transmissive support and a
reflective metal layer. In an embodiment, the one or more sensors
302 include a biological molecule capture layer. In an embodiment,
the biological molecule capture layer includes an array of
different binding molecules that specifically bind one or more
target molecules. In an embodiment, the one or more sensors 302
include a surface plasmon resonance microarray sensor having an
array of micro-regions configured to capture target molecules.
[0231] In an embodiment, the one or more sensors 302 include one or
more acoustic biosensors, amperometric biosensors, calorimetric
biosensors, optical biosensors, or potentiometric biosensors. In an
embodiment, the one or more sensors 302 include one or more fluid
flow sensors. In an embodiment, the one or more sensors 302 include
one or more differential electrodes. In an embodiment, the one or
more sensors 302 include one or more biomass sensors. In an
embodiment, the one or more sensors 302 include one or more
immunosensors.
[0232] In an embodiment, the sensor 302 is operably coupled to a
microorganism colonization biomarker array. In an embodiment, the
sensor 302 includes a biological molecule capture layer. In an
embodiment, the sensor 302 includes a biological molecule capture
layer having an array of different binding molecules that
specifically bind one or more target molecules. In an embodiment,
the sensor 302 includes one or more computing devices 230 operably
coupled to one or more sensors. For example, in an embodiment, the
sensor 302 includes a computing device 230 operably coupled to one
or more surface plasmon resonance microarray sensors.
[0233] In an embodiment, the sensor 302 is configured to detect at
least one attribute associated with a biological subject 222. In an
embodiment, the at least one attribute includes at least one of
physiological condition, genetic profile, proteomic profile,
genetic characteristic, proteomic characteristic, response to
previous treatment, weight, height, medical diagnosis, familial
background, results of one or more medical tests, ethnic
background, body mass index, age, presence or absence of at least
one disease or condition, species, ethnicity, race, allergies,
gender, presence or absence of at least one biological or chemical
agent in the subject, pregnancy status, lactation status, medical
history, or blood condition.
[0234] In an embodiment, the at least one characteristic associated
with a biological sample 808 proximate the insertable device 102
includes at least one of a transmittance, an energy frequency
change, a frequency shift, an energy phase change, or a phase
shift. In an embodiment, the at least one characteristic includes
at least one of a fluorescence, an intrinsic fluorescence, a tissue
fluorescence, or a naturally occurring fluorophore fluorescence. In
an embodiment, the at least one characteristic includes at least
one of an electrical conductivity, and electrical polarizability,
or an electrical permittivity. In an embodiment, the at least one
characteristic associated with a biological sample 808 proximate
the insertable device 102 includes at least one of a thermal
conductivity, a thermal diffusivity, a tissue temperature, or a
regional temperature.
[0235] In an embodiment, the at least one characteristic associated
with a biological sample 808 proximate the insertable device 102
includes information related to metabolism or biological response
to an anti-microbial agent or other anti-microbial surface property
204.
[0236] In an embodiment, the at least one characteristic associated
with a biological sample 808 proximate the insertable device 102
includes at least one parameter associated with a doppler optical
coherence tomograph. (See, e.g., Li et al., Feasibility of
Interstitial Doppler Optical Coherence Tomography for In vivo
Detection of Microvascular Changes During Photodynamic Therapy,
Lasers in Surgery and Medicine 38(8):754-61. (2006), which is
incorporated herein by reference; see, also U.S. Pat. No. 7,365,859
(issued Apr. 29, 2008), which is incorporated herein by
reference).
[0237] In an embodiment, the at least one characteristic associated
with a biological sample 808 proximate the insertable device 102
includes spectral signature information associated with an implant
device. For example, in an embodiment, the at least one
characteristic associated with a biological sample 808 proximate
the insertable device 102 includes implant device spectral
signature information associated with at least one of a
bio-implants, (e.g., bioactive implants, facial implants, buttock
implants, breast implants, cochlear implants, dental implants,
neural implants, orthopedic implants, ocular implants,) prostheses,
implantable electronic device, implantable medical devices, and the
like. Further non-limiting examples of implant devices include
replacements implants (e.g., artificial joint implants, or the like
such as knee, shoulder, wrists elbow, or hip replacements implants,
or the like), subcutaneous drug delivery devices (e.g., implantable
pills, drug-eluting stents, or the like), shunts (e.g., cardiac
shunts, lumbar-peritoneal shunts, cerebrospinal fluid shunts,
cerebral shunts, pulmonary shunts, portosystemic shunts, portacaval
shunts, or the like), stents (e.g., coronary stents, peripheral
vascular stents, prostatic stents, ureteral stents, vascular
stents, or the like), urological catheters, central lines, surgical
drains, biological fluid flow controlling implants, and the like.
Further non-limiting examples of implant device include artificial
hearts, endoscopes, valves (e.g., heart valves), surgical drains,
stomach partition clip, artificial prosthetics, catheters, contact
lens, mechanical heart valves, subcutaneous sensors, urinary
catheters, vascular catheters, and the like.
[0238] In an embodiment, the at least one characteristic includes
at least one parameter associated with a medical state (e.g.,
medical condition, disease state, disease attributes, etc.).
Inflammation is a complex biological response to insults that can
arise from, for example, chemical, traumatic, or infectious
stimuli. It is a protective attempt by an organism to isolate and
eradicate the injurious stimuli as well as to initiate the process
of tissue repair. The events in the inflammatory response are
initiated by a complex series of interactions involving
inflammatory mediators, including those released by immune cells
and other cells of the body. Histamines and eicosanoids such as
prostaglandins and leukotrienes act on blood vessels at the site of
infection to localize blood flow, concentrate plasma proteins, and
increase capillary permeability.
[0239] Chemotactic factors, including certain eicosanoids,
complement, and especially cytokines known as chemokines, attract
particular leukocytes to the site of infection. Other inflammatory
mediators, including some released by the summoned leukocytes,
function locally and systemically to promote the inflammatory
response. Platelet activating factors and related mediators
function in clotting, which aids in localization and can trap
pathogens. Certain cytokines, interleukins and TNF, induce further
trafficking and extravasation of immune cells, hematopoiesis,
fever, and production of acute phase proteins. Once signaled, some
cells and/or their products directly affect the offending
pathogens, for example by inducing phagocytosis of bacteria or, as
with interferon, providing antiviral effects by shutting down
protein synthesis in the host cells.
[0240] Oxygen radicals, cytotoxic factors, and growth factors can
also be released to fight pathogen infection or to facilitate
tissue healing. This cascade of biochemical events propagates and
matures the inflammatory response, involving the local vascular
system, the immune system, and various cells within the injured
tissue. Under normal circumstances, through a complex process of
mediator-regulated pro-inflammatory and anti-inflammatory signals,
the inflammatory response eventually resolves itself and subsides.
For example, the transient and localized swelling associated with a
cut is an example of an acute inflammatory response. However, in
certain cases resolution does not occur as expected. Prolonged
inflammation, known as chronic inflammation, leads to a progressive
shift in the type of cells present at the site of inflammation and
is characterized by simultaneous destruction and healing of the
tissue from the inflammatory process, as directed by certain
mediators. Rheumatoid arthritis is an example of a disease
associated with persistent and chronic inflammation.
[0241] Non-limiting suitable techniques for optically measuring a
diseased state may be found in, for example, U.S. Pat. No.
7,167,734 (issued Jan. 23, 2007), which is incorporated herein by
reference. In an embodiment, the at least one characteristic of a
biological sample 808 proximate the insertable device 102 includes
at least one of an electromagnetic energy absorption parameter, an
electromagnetic energy emission parameter, an electromagnetic
energy scattering parameter, an electromagnetic energy reflectance
parameter, or electromagnetic energy depolarization parameter. In
an embodiment, the at least one characteristic includes at least
one of an absorption coefficient, an extinction coefficient, and a
scattering coefficient.
[0242] In an embodiment, the at least one characteristic of a
biological sample 808 proximate the insertable device 102 includes
at least one parameter associated with an infection marker (e.g.,
an infectious agent marker), an inflammation marker, an infective
stress marker, a systemic inflammatory response syndrome marker, or
a sepsis marker. Non-limiting examples of infection makers,
inflammation markers, and the like may be found in, for example,
Imam et al., Radiotracers for Imaging of Infection and
Inflammation--A Review, World J. Nucl. Med. 40-55 (2006), which is
incorporated herein by reference. Non-limiting characteristics
associated with an infection marker, an inflammation marker, an
infective stress marker, a systemic inflammatory response syndrome
marker, or a sepsis marker include at least one of an inflammation
indication parameter, an infection indication parameter, a diseased
state indication parameter, or a diseased tissue indication
parameter.
[0243] In an embodiment, the at least one characteristic of a
biological sample 808 proximate the insertable device 102 includes
at least one of tissue water content, oxy-hemoglobin concentration,
deoxyhemoglobin concentration, oxygenated hemoglobin absorption
parameter, deoxygenated hemoglobin absorption parameter, tissue
light scattering parameter, tissue light absorption parameter,
hematological parameter, or pH level.
[0244] In an embodiment, the at least one characteristic includes a
physiological characteristic of the biological subject 222.
Physiological characteristics such as, for example pH can be used
to assess blood flow, a cell metabolic state (e.g., anaerobic
metabolism, or the like), the presence of an infectious agent, a
disease state, and the like. Among physiological characteristics
examples include, but are not limited to, at least one of a
temperature, a regional or local temperature, a pH, an impedance, a
density, a sodium ion level, a calcium ion level, a potassium ion
level, a glucose level, a lipoprotein level, a cholesterol level, a
triglyceride level, a hormone level, a blood oxygen level, a pulse
rate, a blood pressure, an intracranial pressure, a respiratory
rate, a vital statistic, and the like.
[0245] In an embodiment, the at least one characteristic includes
at least one of a temperature, a pH, an impedance, a density, a
sodium ion level, a calcium ion level, a potassium ion level, a
glucose level, a lipoprotein level, a cholesterol level, a
triglyceride level, a hormone level, a blood oxygen level, a pulse
rate, a blood pressure, an intracranial pressure, and a respiratory
rate. In an embodiment, the at least one characteristic includes at
least one hematological parameter. In an embodiment, the
hematological parameter is associated with a hematological
abnormality.
[0246] In an embodiment, the at least one characteristic of the
biological sample 808 proximate the insertable device 102 includes
at least one hematological parameter. Non-limiting examples of
hematological parameters include an albumin level, a blood urea
level, a blood glucose level, a globulin level, a hemoglobin level,
erythrocyte count, a leukocyte count, or the like. In an
embodiment, the infection marker includes at least one parameter
associated with a red blood cell count, a lymphocyte level, a
leukocyte count, a myeloid count, an erythrocyte sedimentation
rate, or a C-reactive protein level. In an embodiment, the at least
one characteristic includes at least one parameter associated with
a cytokine plasma level or an acute phase protein plasma level. In
an embodiment, the at least one characteristic includes at least
one parameter associated with a leukocyte level.
[0247] In an embodiment, the at least one characteristic of a
biological sample 808 proximate the insertable device 102 includes
a spectral parameter associated with a biofilm-specific tag. In an
embodiment, the at least one characteristic includes at least one
of an optical density, opacity, refractivity, absorbance,
fluorescence, or transmittance. In an embodiment, the at least one
characteristic includes at least one of an inflammation indication
parameter, infection indication parameter, diseased state
indication parameter, or diseased tissue indication parameter. In
an embodiment, the at least one characteristic includes at least
one of an electromagnetic energy absorption parameter,
electromagnetic energy emission parameter, electromagnetic energy
scattering parameter, electromagnetic energy reflectance parameter,
or electromagnetic energy depolarization parameter. In an
embodiment, the at least one characteristic includes at least one
of an absorption coefficient, extinction coefficient, scattering
coefficient, or fluorescence coefficient. In an embodiment, the at
least one characteristic includes at least one of parameter
associated with at least one of a biomarker, infection marker,
inflammation marker, infective stress marker, or sepsis marker.
[0248] In an embodiment, the at least one characteristic includes
at least one of an electromagnetic energy phase shift parameter, an
electromagnetic energy dephasing parameter, and an electromagnetic
energy depolarization parameter. In an embodiment, the at least one
characteristic includes at least one of an absorbance, a
reflectivity, and a transmittance. In an embodiment, the at least
one characteristic includes at least one of a refraction and a
scattering.
[0249] In an embodiment, the sensor 302 is configured to determine
at least one characteristic associated with one or more biological
markers or biological components (e.g., cerebrospinal fluid
components, blood components, or the like). In an embodiment, the
sensor 302 is configured to determine at least one characteristic
associated with a biological sample proximate the insertable device
102. In an embodiment, the sensor 302 is configured to determine a
spatial dependence associated with the least one characteristic
associated with a biological sample. In an embodiment, the sensor
302 is configured to determine a temporal dependence associated
with the least one characteristic associated with a biological
sample. In an embodiment, the sensor 302 is configured to
concurrently or sequentially determine at least one spatial
dependence associated with the least one characteristic associated
with a biological sample, and at least one temporal dependence
associated with the least one characteristic associated with a
biological sample.
[0250] In an embodiment, the sensor 302 is configured to determine
at least one spectral parameter associated with one or more imaging
probes (e.g., chromophores, fluorescent agents, fluorescent marker,
fluorophores, molecular imaging probes, quantum dots,
radio-frequency identification transponders (RFIDs), x-ray contrast
agents, or the like). In an embodiment, the sensor 302 is
configured to determine at least one characteristic associated with
one or more imaging probes attached, targeted to, conjugated,
bound, or associated with at least one inflammation markers. See,
e.g., the following documents (the contents of each of which is
incorporated herein by reference): Jaffer et al., Arterioscler.
Thromb. Vasc. Biol. 2002; 22; 1929-1935 (2002); Kalchenko et al.,
J. of Biomed. Opt. 11(5):050507 (2006).
[0251] In an embodiment, the one or more imaging probes include at
least one carbocyanine dye label. In an embodiment, the sensor 302
is configured to determine at least one characteristic associated
with one or more imaging probes attached, targeted to, conjugated,
bound, or associated with at least one biomarker or biological
sample component (e.g. biological tissue component, or biological
fluid component, etc.).
[0252] In an embodiment, the one or more imaging probes include at
least one of a fluorescent agen, quantum dot, radio-frequency
identification transponder, x-ray contrast agent, or molecular
imaging probe.
[0253] Further non-limiting examples of imaging probes include
fluorescein (FITC), indocyanine green (ICG), and rhodamine B.
Non-limiting examples of other fluorescent dyes for use in
fluorescence imaging include a number of red and near infrared
emitting fluorophores (600-1200 nm) including cyanine dyes such as
Cy5, Cy5.5, and Cy7 (Amersham Biosciences, Piscataway, N.J., USA)
or a variety of Alexa Fluor dyes such as Alexa Fluor 633, Alexa
Fluor 635, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa
Fluor 700, Alexa Fluor 750 (Molecular Probes-Invitrogen, Carlsbad,
Calif., USA; see, also, U.S. Patent Pub. No. 2005/0171434
(published Aug. 4, 2005) (the contents of each of which is
incorporated herein by reference), and the like.
[0254] Further non-limiting examples of imaging probes include
IRDye800, IRDye700, and IRDye680 (LI-COR, Lincoln, Nebr., USA),
NIR-1 and 1C5-OSu (Dejindo, Kumamotot, Japan), LaJolla Blue
(Matron, Miami, Fla., USA), FAR-Blue, FAR-Green One, and FAR-Green
Two (Innosense, Giacosa, Italy), ADS 790-NS, ADS 821-NS (American
Dye Source, Montreal, Calif.), NIAD-4 (ICx Technologies, Arlington,
Va.), and the like. Further non-limiting examples of fluorophores
include BODIPY-FL, europium, green, yellow and red fluorescent
proteins, luciferase, and the like. Quantum dots of various
emission/excitation properties can be used as imaging probes. See,
e.g., Jaiswal, et al. Nature Biotech. 21:47-51 (2003) (the contents
of each of which is incorporated herein by reference). Further
non-limiting examples of imaging probes include those including
antibodies specific for leukocytes, anti-fibrin antibodies,
monoclonal anti-diethylene triamine pentaacetic acid (DTPA), DTPA
labeled with Technetium-99m (.sup.99mTC), and the like.
[0255] Further non-limiting examples of biomarkers include
high-sensitivity C-reactive protein (hs-CRP), cardiac troponin T
(cTnT), cardiac troponin I (cTnI), N-terminal-pro B-type
natriuretic peptide (NT-proBNP), D-dimer, P-selectin, E-selectin,
thrombin, interleukin-10, fibrin monomers, phospholipid
microparticles, creatine kinase, interleukin-6, tumor necrosis
factor-alpha, myeloperoxidase, intracellular adhesion molecule-1
(ICAM1), vascular adhesion molecule (VCAM), matrix
metalloproteinase-9 (MMP9), ischemia modified albumin (IMA), free
fatty acids, choline, soluble CD40 ligand, insulin-like growth
factor, (see, e.g., Giannitsis, et al. Risk stratification in
pulmonary embolism based on biomarkers and echocardiography. Circ.
112:1520-1521 (2005), Barnes, et al., Novel biomarkers associated
with deep venous throbosis: A comprehensive review. Biomarker
Insights 2:93-100 (2008); Kamphuisen, Can anticoagulant treatment
be tailored with biomarkers in patients with venous
thromboembolism? J. Throm. Haemost. 4:1206-1207 (2006); Rosalki, et
al., Cardiac biomarkers for detection of myocardial infarction:
Perspectives from past to present. Clin. Chem. 50:2205-2212 (2004);
Apple, et al., Future biomarkers for detection of ischemia and risk
stratification in. acute coronary syndrome, Clin. Chem. 51:810-824
(2005), each of which is incorporated herein by reference).
[0256] In an embodiment, the sensor 302 is configured to detect a
spectral response 299 (e.g., an emitted energy, a remitted energy,
an energy absorption profile, energy emission profile, or the like)
associated with a biomarker. Among biomarker examples include, but
are not limited to, one or more substances that are measurable
indicators of a biological state and can be used as indicators of
normal disease state, pathological disease state, and/or risk of
progressing to a pathological disease state. In some instances, a
biomarker can be a normal blood component that is increased or
decreased in the pathological state. A biomarker can also be a
substance that is not normally detected in biological sample 808
(e.g. a biological fluid, or tissue), but is released into
circulation because of the pathological state. In some instances, a
biomarker can be used to predict the risk of developing a
pathological state. For example, plasma measurement of
lipoprotein-associated phospholipase A2 (Lp-PLA2) is approved by
the U.S. Food & Drug Administration (FDA) for predicting the
risk of first time stroke.
[0257] In other instances, the biomarker can be used to diagnose an
acute pathological state. For example, elevated plasma levels of
S-100b, B-type neurotrophic growth factor (BNGF), von Willebrand
factor (vWF), matrix metalloproteinase-9 (MMP-9), and monocyte
chemoattractant protein-1 (MCP-1) are highly correlated with the
diagnosis of stroke (see, e.g., Reynolds, et al., Early biomarkers
of stroke. Clin. Chem. 49:1733-1739 (2003), which is incorporated
herein by reference).
[0258] In an embodiment, the sensor 302 is configured to detect at
least one characteristic associated with one or more biological
sample components. In an embodiment, the at least one
characteristic includes at least one of absorption coefficient
information, extinction coefficient information, or scattering
coefficient information associated with the at least one molecular
probe. In an embodiment, the at least one characteristic includes
spectral information indicative of at least one of rate of change,
accumulation rate, aggregation rate, or rate of change associated
with at least one physical parameter associated with a biological
sample component.
[0259] In an embodiment, the sensor 302 is configured to detect
spectral information associated with a real-time change in one or
more parameters associated with a biological sample 808 (e.g.,
biological tissue or fluid). For example, in an embodiment, the
sensor 302 is configured to detect at least one of an emitted
energy and a remitted energy associated with a real-time change in
one or more parameters associated with a biological sample 808
within one or more anti-microbial regions of an insertable device
102. In an embodiment, the sensor 302 includes one or more
transducers configured to detect sound waves associated with
changes in a biological sample 808 present proximate at least one
of the outer surface 106 or the inner surface 108 of the body
structure 104.
[0260] In an embodiment, the sensor 302 is configured to detect at
least one of an emitted energy and a remitted energy. In an
embodiment, the sensor 302 is configured to detect at least one of
an emitted energy and a remitted energy associated with a
biological subject 222. In an embodiment, the sensor 302 is
configured to detect an optical energy absorption profile of a
target sample, a portion of a tissue, or portion of a biological
sample 808 (e.g., biological tissue or fluid) within the biological
subject 222. In an embodiment, the sensor 302 is configured to
detect an excitation radiation and an emission radiation associated
with a portion of a target sample, a portion of a tissue, or
portion of a biological sample 808 within the biological subject
222. In an embodiment, the sensor 302 is configured to detect at
least one of an energy absorption profile and an energy reflection
profile of a region within a biological subject 222.
[0261] In an embodiment, the sensor 302 is configured to detect a
spectral response 299 from a biological sample 808 of a biological
subject 222. Blood is a tissue composed of, among other components,
formed elements (e.g., blood cells such as erythrocytes,
leukocytes, thrombocytes, or the like) suspend in a matrix
(plasma). The heart, blood vessels (e.g., arteries, arterioles,
capillaries, veins, venules, or the like), and blood components,
make up the cardiovascular system. The cardiovascular system, among
other things, moves oxygen and other gases, as well as other
biochemical agents to and from cells and tissues, maintains
homeostasis by stabilizing body temperature and pH, and helps fight
diseases.
[0262] In an embodiment, the sensor 302 is configured to detect at
least one of an emitted energy and a remitted energy associated
with a portion of a cardiovascular system. In an embodiment, the
sensor 302 is configured to detect at least one of an emitted
energy and a remitted energy associated with one or more blood
components within a biological subject 222. In an embodiment, the
sensor 302 is configured to detect at least one of an emitted
energy and a remitted energy associated with one or more formed
elements within a biological subject 222. In an embodiment, the
sensor 302 is configured to detect spectral information associated
with one or more of one or more blood components. In an embodiment,
the sensor 302 is configured to detect at least one of an emitted
energy and a remitted energy associated with a real-time change in
one or more parameters associated with at least one blood component
within a biological subject 222. In an embodiment, the sensor 302
is configured to detect an energy absorption of one or more blood
components.
[0263] Non-limiting examples of detectable blood components include
erythrocytes, leukocytes (e.g., basophils, granulocytes,
eosinophils, monocytes, macrophages, lymphocytes, neutrophils, or
the like), thrombocytes, acetoacetate, acetone, acetylcholine,
adenosine triphosphate, adrenocorticotrophic hormone, alanine,
albumin, aldosterone, aluminum, amyloid proteins
(non-immunoglobulin), antibodies, apolipoproteins, ascorbic acid,
aspartic acid, bicarbonate, bile acids, bilirubin, biotin, blood
urea, nitrogen, bradykinin, bromide, cadmium, calciferol,
calcitonin (ct), calcium, carbon dioxide, carboxyhemoglobin (as
HbcO), cell-related plasma proteins, cholecystokinin
(pancreozymin), cholesterol, citric acid, citrulline, complement
components, coagulation factors, coagulation proteins, complement
components, c-peptide, c-reactive protein, creatine, creatinine,
cyanide, 11-deoxycortisol, deoxyribonucleic acid,
dihydrotestosterone, diphosphoglycerate (phosphate), or the
like.
[0264] Further non-limiting examples of detectable blood components
include dopamine, enzymes, epidermal growth factor, epinephrine,
ergothioneine, erythrocytes, erythropoietin, folic acid, fructose,
furosemide glucuronide, galactoglycoprotein, galactose (children),
gamma-globulin, gastric inhibitory peptide, gastrin, globulin,
.alpha.-1-globulin, .alpha.-2-globulin, .alpha.-globulins,
.beta.-globulins, glucagon, glucosamine, glucose, immunoglobulins
(antibodies), lipase p, lipids, lipoprotein (sr 12-20), lithium,
low-molecular weight proteins, lysine., lysozyme (muramidase),
.alpha.-2-macroglobulin, .gamma.-mobility (non-immunoglobulin),
pancreatic polypeptide, pantothenic acid, para-aminobenzoic acid,
parathyroid hormone, pentose, phosphorated, phenol, phenylalanine,
phosphatase, acid, prostatic, phospholipid, phosphorus, prealbumin,
thyroxine-binding, proinsulin, prolactin (female), prolactin
(male), proline, prostaglandins, prostate specific antigen,
protein, protoporphyrin, pseudoglobulin I, pseudoglobulin II,
purine, pyridoxine, pyrimidine nucleotide, pyruvic acid, CCL5
(RANTES), relaxin, retinol, retinol-binding protein, riboflavin,
ribonucleic acid, secretin, serine, serotonin
(5-hydroxytryptamine), silicon, sodium, solids, somatotropin
(growth hormone), sphingomyelin, succinic acid, sugar, sulfates,
inorganic, sulfur, taurine, testosterone (female), testosterone
(male), triglycerides, triiodothyronine, tryptophan, tyrosine,
urea, uric acid, water, miscellaneous trace components, and the
like.
[0265] Non-limiting examples of .alpha.-globulins examples include
.alpha.1-acid glycoprotein, .alpha.1-antichymotrypsin,
.alpha.1-antitrypsin, .alpha.1B-glycoprotein, .alpha.1-fetoprotein,
.alpha.1-microglobulin, .alpha.1T-glycoprotein,
.alpha.2HS-glycoprotein, .alpha.2-macroglobulin, 3.1 S Leucine-rich
.alpha.2-glycoprotein, 3.8 S histidine-rich .alpha.2-glycoprotein,
4 S .alpha.2,.alpha.1-glycoprotein, 8 S .alpha.3-glycoprotein, 9.5
S .alpha.1-glycoprotein (serum amyloid P protein),
Corticosteroid-binding globulin, ceruloplasmin, GC globulin,
haptoglobin (e.g., Type 1-1, Type 2-1, or Type 2-2),
inter-.alpha.-trypsin inhibitor, pregnancy-associated
.alpha.2-glycoprotein, serum cholinesterase, thyroxine-binding
globulin, transcortin, vitamin D-binding protein,
Zn-.alpha.2-glycoprotein, and the like. Among .beta.-Globulins,
examples include, but are not limited to, hemopexin, transferrin,
.beta.2-microglobulin, .beta.2-glycoprotein I, .beta.2-glycoprotein
II, (C3 proactivator), .beta.2-glycoprotein III, C-reactive
protein, fibronectin, pregnancy-specific .beta.1-glycoprotein,
ovotransferrin, and the like. Among immunoglobulins examples
include, but are not limited to, immunoglobulin G (e.g., IgG,
IgG.sub.1, IgG.sub.2, IgG.sub.3, IgG.sub.4), immunoglobulin A
(e.g., IgA, IgA.sub.1, IgA.sub.2), immunoglobulin M, immunoglobulin
D, immunoglobulin E, .kappa. Bence Jones protein, .gamma. Bence
Jones protein, J Chain, and the like.
[0266] Among apolipoproteins examples include, but are not limited
to, apolipoprotein A-I (HDL), apolipoprotein A-II (HDL),
apolipoprotein C-I (VLDL), apolipoprotein C-II, apolipoprotein
C-III (VLDL), apolipoprotein E, and the like. Among
.gamma.-mobility (non-immunoglobulin) examples include, but are not
limited to, 0.6 S .gamma.2-globulin, 2 S .gamma.2-globulin, basic
Protein B2, post-.gamma.-globulin (.gamma.-trace), and the like.
Among low-molecular weight proteins examples include, but are not
limited to, lysozyme, basic protein B1, basic protein B2, 0.6 S
.gamma.2-globulin, 2 S .gamma.2-globulin, post .gamma.-globulin,
and the like.
[0267] Among complement components examples include, but are not
limited to, C1 esterase inhibitor, C1q component, C1r component,
C1s component, C2 component, C3 component, C3a component,
C3b-inactivator, C4 binding protein, C4 component, C4a component,
C4-binding protein, C5 component, C5a component, C6 component, C7
component, C8 component, C9 component, factor B, factor B (C3
proactivator), factor D, factor D (C3 proactivator convertase),
factor H, factor H(NH), properdin, and the like. Among coagulation
proteins examples include, but are not limited to, antithrombin
III, prothrombin, antihemophilic factor (factor VIII), plasminogen,
fibrin-stabilizing factor (factor XIII), fibrinogen, thrombin, and
the like.
[0268] Among cell-related plasma proteins examples include, but are
not limited to, fibronectin, .beta.-thromboglobulin, platelet
factor-4, serum Basic Protease Inhibitor, and the like. Among
amyloid proteins (Non-Immunoglobulin) examples include, but are not
limited, to, amyloid-Related apoprotein (apoSAA1), AA (FMF) (ASF),
AA (TH) (AS), serum amyloid P component (9.5 S
7.alpha.1-glycoprotein), and the like. Among miscellaneous trace
components examples include, but are not limited to,
varcinoembryonic antigen, angiotensinogen, and the like.
[0269] In an embodiment, the sensor 302 is configured to detect a
spectral response 299 associated with a real-time change in one or
more parameters associated with at least one biological sample 808
component (e.g., a cerebrospinal fluid component). Non-limiting
examples of detectable cerebrospinal fluid components include
adenosine deaminase, albumin, calcium, chloride, C-reactive
protein, creatine kinase, creatinine, cystatin C, cytokines,
glucose, hydrogencarbonate, immunoglobulin G, interleukins,
lactate, lactate dehydrogenase, lipids, lymphocytes, monocytes,
mononuclear cells, myelin basic protein, neuron-specific enolase,
potassium, proteins, S-100 protein, small molecules, sodium,
.beta..sub.2-microglobulin, and the like.
[0270] In an embodiment, the sensor 302 is in optical communication
along an optical path with at least one of the energy emitters 220.
In an embodiment, one or more of the energy emitters 220 are
configured to direct an in vivo generated pulsed energy stimulus
along an optical path for a duration sufficient to interact with
one or more regions within the biological subject 222 and for a
duration sufficient for a portion of the in vivo generated pulsed
energy stimulus to reach a portion of the sensor 302 that is in
optical communication along the optical path. In an embodiment, one
or more of the energy emitters 220 are configured to direct optical
energy along an optical path for a duration sufficient to interact
with one or more regions within the biological subject 222 and with
at least a portion of the optical energy sensor 302. In an
embodiment, one or more of the energy emitters 220 are configured
to emit a pulsed optical energy stimulus along an optical path for
a duration sufficient to interact with a sample received within the
one or more fluid-flow passageways 110, such that a portion of the
pulsed optical energy stimulus is directed to a portion of the
sensor 302 that is in optical communication along the optical
path.
[0271] As indicated in FIG. 3, in an embodiment, the at least one
anti-microbial region 202 including at least one anti-microbial
agent is configured to release the anti-microbial agent over time.
In an embodiment, the anti-microbial agent includes a microbial
tactic agent. In an embodiment, the microbial tactic agent includes
at least one chemotactic agent. In an embodiment, the at least one
microbial tactic agent includes at least one attractant or
repellant surface property. In an embodiment, the repellant surface
property is located proximate to a protected site 310. In an
embodiment, the repellant surface property encircles a protected
site 310. In an embodiment, the protected site 310 or the
destructive site 305 includes at least one of a port 118, or sensor
302.
[0272] In an embodiment, the insertable device 102 comprises a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; a plurality of
anti-microbial regions 202 arranged in at least one pattern 109
(e.g., spatial pattern or temporal pattern), one or more of the
anti-microbial regions 202 included on at least one of the outer
surface 106 or the inner surface 108, or embedded in the body
structure 104.
[0273] In an embodiment, the system 100 is configured to compare an
input associated with at least one characteristic associated with a
biological sample 808 proximate the insertable device 102 (e.g.,
received within one or more fluid-flow passageways 110, proximate
(e.g., on or near) a surface of the body structure 104, or the
like) to a database 258 of stored reference values, and to generate
a response 299 based in part on the comparison. In an embodiment,
the response 299 includes at least one of a visual representation,
audio representation (e.g., alarm, audio waveform representation of
a tissue region, or the like), haptic representation, or tactile
representation (e.g., tactile diagram, tactile display, tactile
graph, tactile interactive depiction, tactile model (e.g.,
multidimensional model of an infected tissue region, or the like),
tactile pattern (e.g., refreshable Braille display), tactile-audio
display, tactile-audio graph, or the like). In an embodiment, the
response 299 includes generating at least one of a visual, audio,
haptic, or tactile representation of biological sample 808 spectral
information (e.g., biological fluid spectral information, tissue
spectral information, fat spectral information, muscle spectral
information, bone spectral information, blood component spectral
information, biomarker spectral information, infectious agent
spectral information, and the like). In an embodiment, the response
299 includes generating at least one of a visual, audio, haptic, or
tactile representation of at least one physical or biochemical
characteristic associated with a biological subject 222.
[0274] In an embodiment, the response 299 includes initiating one
or more treatment protocols. In an embodiment, the response 299
includes activating one or more sterilization protocols. In an
embodiment, the response 299 includes initiating at least one
treatment regimen. In an embodiment, the response 299 includes
delivering an energy stimulus. In an embodiment, the response 299
includes delivering an active agent (e.g., anti-microbial agent).
In an embodiment, the response 299 includes concurrently or
sequentially delivering an energy stimulus and an active agent
(e.g., anti-microbial agent).
[0275] In an embodiment, the response 299 includes at least one of
a response signal, a control signal, a change to a sterilizing
stimulus parameter (e.g., an electrical sterilizing stimulus,
electromagnetic sterilizing stimulus, acoustic sterilizing
stimulus, or thermal sterilizing stimulus), or the like. In an
embodiment, the response 299 includes at least one of a change in
an excitation intensity, change in an excitation frequency, change
in an excitation pulse frequency, change in an excitation pulse
ratio, change in an excitation pulse intensity, change in an
excitation pulse duration time, change in an excitation pulse
repetition rate, or the like.
[0276] In an embodiment, the response 299 includes at least one of
activating an authorization protocol 300, activating an
authentication protocol 301, activating a software update protocol
333, activating a data transfer protocol 303, or activating an
infection sterilization diagnostic protocol 304. In an embodiment,
the response 299 includes sending information associated with at
least one of an authentication protocol 301, authorization protocol
300, delivery protocol 305, activation protocol 306, encryption
protocol 307, or 308 decryption protocol.
[0277] In an embodiment, the system 100 is configured to compare an
input associated with a biological subject 222 to a database 258 of
stored reference values, and to generate a response 299 based in
part on the comparison. In an embodiment, the system 100 is
configured to compare an output of one or more of the plurality of
logic components and to determine at least one parameter associated
with a cluster centroid deviation derived from the comparison. In
an embodiment, the system 100 is configured to compare a measurand
associated with the biological subject 222 to a threshold value
associated with a spectral model and to generate a response 299
based on the comparison. In an embodiment, the system 100 is
configured to generate the response 299 based on the comparison of
a measurand that modulates with a detected heart beat of the
biological subject 222 to a target value associated with a spectral
model.
[0278] In an embodiment, the system 100 is configured to compare
the measurand associated with the biological subject 222 to the
threshold value associated with a spectral model and to generate a
real-time estimation of an infection state based on the comparison.
In an embodiment, the system 100 is configured to compare an input
associated with at least one characteristic associated with, for
example, a biological sample proximate an insertable device 102 to
a database 258 of stored reference values, and to generate a
response 299 based in part on the comparison.
[0279] As described in FIG. 7, the system 100 can include, among
other things, one or more data structures (e.g., physical data
structures) 260. In an embodiment, a data structure 260 includes
information associated with at least one parameter associated with
a tissue water content, an oxy-hemoglobin concentration, a
deoxyhemoglobin concentration, an oxygenated hemoglobin absorption
parameter, a deoxygenated hemoglobin absorption parameter, a tissue
light scattering parameter, a tissue light absorption parameter, a
hematological parameter, a pH level, or the like. The system 100
can include, among other things, at least one of inflammation
indication parameter data, infection indication parameter data,
diseased tissue indication parameter data, or the like configured
as a data structure 260. In an embodiment, a data structure 260
includes information associated with least one parameter associated
with a cytokine plasma concentration or an acute phase protein
plasma concentration. In an embodiment, a data structure 260
includes information associated with a disease state of a
biological subject 222. In an embodiment, a data structure 260
includes measurement data. In an embodiment, the computing device
230 includes a processor 232 configured to execute instructions,
and a memory 250 that stores instructions configured to cause the
processor 232 to generate a second response from information
encoded in a data structure 260.
[0280] In an embodiment, an insertable device 102 includes: a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; at least one
anti-microbial region 202 configured to deliver at least one
anti-microbial agent to one or more areas of at least one of the
outer surface 106, the inner surface 108 or embedded in the
internal body structure 104; a sensor 302 configured to detect at
least one microbial component proximate at least one of the outer
surface 106 or the inner surface 108 of the body structure 104; and
one or more computer-readable memory media 262 having microbial
marker information configured as a data structure 260, the data
structure 260 including a characteristic information section having
characteristic microbial information representative of the presence
of at least one microorganism proximate at least one of the outer
surface 106 or the inner surface 108 of the body structure 104, or
the interior of the fluid-flow passageway 110.
[0281] In an embodiment, the at least one sensor 302 is operably
associated with at least one of the anti-microbial regions 202. In
an embodiment, the at least one sensor 302 is configured to detect
the presence of at least one microorganism proximate at least one
of the inner surface 108 or the outer surface 106 of the one or
more fluid-flow passageways 110. In an embodiment, the at least one
sensor 302 is configured to detect the presence of at least one
microorganism within the one or more fluid-flow passageways 110
based on one or more flow characteristics. In an embodiment, the at
least one sensor 302 is configured to detect a location associated
with the presence of at least one microorganism. In an embodiment,
the at least one sensor 302 is configured to detect at least one
microbial component. In an embodiment, the at least one sensor 302
includes a microbial component capture layer. In an embodiment, the
microbial capture layer includes an array of different binding
molecules that specifically bind one or more components of at least
one microorganism.
[0282] The system 100 can include, among other things, one or more
computer-readable memory media (CRMM) 262 having biofilm marker
information configured as a data structure 260. In an embodiment,
the data structure 260 includes a characteristic information
section having characteristic microbial component information
representative of the presence of at least one microorganism
proximate at least one of the outer surface 106 or the inner
surface 108 of the body structure 104. In an embodiment, the data
structure 260 includes infection marker information. In an
embodiment, the data structure 260 includes biofilm marker
information. In an embodiment, the data structure 260 includes
biological mass information associated with the presence of at
least one microorganism proximate at least one of the inner surface
108 or the outer surface 106 of the body structure 104. In an
embodiment, the data structure 260 includes a characteristic
information section having characteristic microbial metabolic
information associated with the presence of at least one
microorganism proximate at least one of the inner surface 108, or
the outer surface 106 of the body structure 104. In an embodiment,
the data structure 260 includes a characteristic information
section having characteristic cell surface information associated
with the presence of at least one microorganism proximate at least
one of the inner surface 108, or the outer surface 106 of the body
structure 104.
[0283] In an embodiment, the data structure 260 includes a
characteristic information component including metabolite
information associated with a microorganism presence. In an
embodiment, the data structure 260 includes a characteristic
information component including temporal metabolite information or
spatial metabolite information associated with a microorganism
presence. In an embodiment, the data structure 260 includes a
characteristic information component including oxygen concentration
gradient information associated with a microorganism presence. In
an embodiment, the data structure 260 includes a characteristic
information component including pH information associated with a
microorganism presence. In an embodiment, the data structure 260
includes a characteristic information component including nutrient
information associated with a microorganism presence. In an
embodiment, the data structure 260 includes a characteristic
information component including spectral information associate with
a biofilm-specific tag.
[0284] In an embodiment, the data structure 260 includes a
characteristic information component including optical density
information. In an embodiment, the data structure 260 includes a
characteristic information component including opacity information.
In an embodiment, the data structure 260 includes a characteristic
information component including refractivity information. In an
embodiment, the data structure 260 includes a characteristic
information component including characteristic infection marker
spectral information. In an embodiment, the data structure 260
includes a characteristic information component including
characteristic infective stress marker spectral information. In an
embodiment, the data structure 260 includes a characteristic
information component including characteristic sepsis maker
spectral information.
[0285] In an embodiment, the data structure 260 includes at least
one of psychosis state marker information, psychosis trait marker
information, or psychosis indication information. In an embodiment,
the data structure 260 includes at least one of psychosis state
indication information, psychosis trait indication information, or
predisposition for a psychosis indication information. In an
embodiment, the data structure 260 includes at least one of
infection indication information, inflammation indication
information, diseased state indication information, or diseased
tissue indication information.
[0286] In an embodiment, a data structure 260 includes biological
sample spectral information. In an embodiment, the data structure
260 includes one or more heuristically determined parameters
associated with at least one in vivo or in vitro determined metric.
For example, information associated with a biological sample 808
can be determined by one or more in vivo or in vitro technologies
or methodologies including, for example, high-resolution proton
magnetic resonance spectroscopy, nanoprobe nuclear magnetic
resonance spectroscopy, in vivo micro-dialysis, flow cytometry, or
the like. Non-limiting examples of heuristics include a heuristic
protocol, heuristic algorithm, threshold information, a threshold
level, a target parameter, or the like. The system 100 can include,
among other things, a means 276 for generating one or more
heuristically determined parameters associated with at least one in
vivo or in vitro determined metric including one or more data
structures 260. The system 100 can include, among other things, a
means 460 for generating a response 299 based on a comparison, of a
detected at least one of an emitted energy and a remitted energy to
at least one heuristically determined parameter, including one or
more data structures 260.
[0287] In an embodiment, a data structure 260 includes one or more
heuristics. In an embodiment, the one or more heuristics include a
heuristic for determining a rate of change associated with at least
one physical parameter associated with a biological sample 808. For
example, in an embodiment, the one or more heuristics include a
heuristic for determining the presence of an infectious agent. In
an embodiment, the one or more heuristics include a heuristic for
determining at least one dimension of an infected tissue region. In
an embodiment, the one or more heuristics include a heuristic for
determining a location of an infection. In an embodiment, the one
or more heuristics include a heuristic for determining a rate of
change associated with a biochemical marker within the one or more
fluid-flow passageways 110.
[0288] In an embodiment, the one or more heuristics include a
heuristic for determining a biochemical marker aggregation rate. In
an embodiment, the one or more heuristics include a heuristic for
determining a type of biochemical marker. In an embodiment, the one
or more heuristics include a heuristic for generating at least one
initial parameter. In an embodiment, the one or more heuristics
include a heuristic for forming an initial parameter set from one
or more initial parameters. In an embodiment, the one or more
heuristics include a heuristic for generating at least one initial
parameter, and for forming an initial parameter set from the at
least one initial parameter. In an embodiment, the one or more
heuristics include at least one pattern classification and
regression protocol.
[0289] In an embodiment, a data structure 260 includes information
associated with at least one parameter associated with a tissue
water content, an oxy-hemoglobin concentration, a deoxyhemoglobin
concentration, an oxygenated hemoglobin absorption parameter, a
deoxygenated hemoglobin absorption parameter, a tissue light
scattering parameter, a tissue light absorption parameter, a
hematological parameter, a pH level, or the like. The system 100
can include, among other things, at least one of inflammation
indication parameter data, infection indication parameter data,
diseased tissue indication parameter data, or the like configured
as a data structure 260. In an embodiment, a data structure 260
includes information associated with least one parameter associated
with a cytokine plasma concentration or an acute phase protein
plasma concentration. In an embodiment, a data structure 260
includes information associated with a disease state of a
biological subject 222. In an embodiment, a data structure 260
includes measurement data.
[0290] The system 100 can include, among other things, one or more
computer-readable media drives 264, interface sockets, Universal
Serial Bus (USB) ports, memory card slots, and the like, and one or
more input/output components 266 such as; for example, a graphical
user interface 268, a display, a keyboard 270, a keypad, a
trackball, a joystick, a touch-screen, a mouse, a switch, a dial,
and the like, and any other peripheral device. In an embodiment,
the system 100 includes one or more user input/output components
266 that operably couple to at least one computing device 230 to
control (electrical, electromechanical, software-implemented,
firmware-implemented, or other control, or combinations thereof) at
least one parameter associated with the energy delivery associated
with one or more of the anti-microbial regions 202.
[0291] In an embodiment, the system 100 includes one or more
instructions that when executed on at least one computing device
230 cause the computing device 230 to generate at least one output
to a user. In an embodiment, the at least one computing device 230
is remote to the insertable device. In an embodiment, the at least
one output includes at least one of a treatment protocol,
identification of a detected microorganism, status of the
insertable device 102, or location of a detected microorganism. In
an embodiment, the user includes at least one entity 555. In an
embodiment, the at least one entity 555 includes at least one
person or computer. In an embodiment, the at least one output
includes output to a user readable display. In an embodiment, the
user readable display is operably coupled to the insertable device
102. In an embodiment, the at least one output is in real-time. In
an embodiment, the at least one output is associated with
historical information. In an embodiment, the user readable display
includes a human readable display. In an embodiment, the user
readable display includes one or more active displays. In an
embodiment, the user readable display includes one or more passive
displays. In an embodiment, the user readable display includes one
or more of a numeric format, graphical format, or audio format.
[0292] In an embodiment, the attractant surface property is located
distal to a protected site 310. In an embodiment, the attractant
surface property is configured to direct one or more microorganisms
away from a protected site 310. In an embodiment, the attractant
surface property is configured to direct one or more microorganisms
toward a destructive site 305. In an embodiment, the at least one
microbial tactic agent includes at least one chemoattractant or
chemorepellant. In an embodiment, the chemoattractant includes at
least one of a carbohydrate, glycopeptides, proteoglycan,
glycolipid, enzyme, lipopolysaccharide, lipid, peptide,
polypeptide, protein, organic, or inorganic molecule. In an
embodiment, the at least one chemoattractant includes at least one
of glucose, formyl peptide, or chemokine. In an embodiment, the at
least one chemorepellent includes at least one of a carbohydrate,
glycopeptides, proteoglycan, glycolipid, lipopolysaccharide,
enzyme, lipid, peptide, polypeptide, protein, organic, or inorganic
molecule. In an embodiment, the at least one chemorepellent
includes at least one of a hormone, oxide, peroxide, alcohol, or
aldehyde. In an embodiment, the at least one chemorepellent
includes at least one of an inorganic salt, amino acid, or
chemokine. In an embodiment, the at least one microbial destructive
site 305 includes at least one anti-microbial agent.
[0293] In an embodiment, the insertable device 102 includes at
least one microbial destructive site 305. In an embodiment, at
least one of the anti-microbial regions 202 includes at least one
gradient 312 (such as a temporal gradient, spatial gradient, or
chemical gradient). In an embodiment, at least one of the
anti-microbial regions 202 includes at least one gradient 312 of
self-assembled monolayers including at least one alkanethiol. In an
embodiment, the at least one alkanethiol includes
HS(CH.sub.2).sub.11(OCH.sub.2CH.sub.2).sub.3OH.
[0294] In an embodiment, the insertable device 102 includes one or
more power sources 900. In an embodiment, the power source 900 is
electromagnetically, magnetically, acoustically, optically,
ultrasonically, inductively, electrically, or capacitively coupled
to the body structure 104. In an embodiment, the power source 900
is coupled to at least one of the anti-microbial regions 202, a
computing device 230, or a sensor 302. Non-limiting examples of
power sources 900 include one or more button cells, chemical
battery cells, a fuel cell, secondary cells, lithium ion cells,
micro-electric patches, nickel metal hydride cells, silver-zinc
cells, capacitors, super-capacitors, thin film secondary cells,
ultra-capacitors, zinc-air cells, or the like. Further non-limiting
examples of power sources 900 include one or more generators (e.g.,
electrical generators, thermo energy-to-electrical energy
generators, mechanical-energy-to-electrical energy generators,
micro-generators, nano-generators, or the like) such as, for
example, thermoelectric generators, piezoelectric generators,
electromechanical generators, biomechanical-energy harvesting
generators, and the like. In an embodiment, the power source 900
includes at least one rechargeable power source 701. In an
embodiment, the power source 900 is carried by the catheter device
102. In an embodiment, the catheter device 102 can include, among
other things, at least one of a battery, a capacitor, and a
mechanical energy store (e.g., a spring, a flywheel, or the like).
In an embodiment, the power source 900 comprises at least one
rechargeable power source 701. In an embodiment, the insertable
device 102 is configured to receive power from an ex vivo power
source. In an embodiment, the power receiver 701 is configured to
receive power from an in vivo power source (e.g., thermoelectric
generator, piezoelectric generator, electromechanical systems
generator, alternating current nanogenerator, biomechanical-energy
harvesting generator, etc.).
[0295] The system 100 can include, among other things, a plurality
of selectively actuatable anti-microbial regions 202a. For example,
in an embodiment, the catheter device 102 includes a plurality of
selectively actuatable anti-microbial regions 202a that define one
or more portions of the body structure 104. In an embodiment, at
least a portion of the outer surface 106 of the body structure 104
includes one or more of the plurality of selectively actuatable
anti-microbial regions 202a. In an embodiment, at least a portion
of the inner surface 108 of the body structure 104 includes one or
more of the plurality of selectively actuatable anti-microbial
regions 202a.
[0296] In an embodiment, the insertable device 102 comprises a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110, the body structure
104 having a plurality of actuatable anti-microbial regions 202a
that are selectively actuatable between at least a first actuatable
state and a second actuatable state; and one or more sensors 302
configured to detect at least one microbial component in a
biological sample 808 proximate at least one of the outer surface
106 or the inner surface 108 of the body structure 104. In an
embodiment, the one or more sensors 302 are configured to detect
one or more microorganisms present proximate to the body structure
104.
[0297] In an embodiment, the insertable device 102 comprises a body
structure 104 defining one or more fluid-flow passageways 110; the
body structure 104 including one or more selectively actuatable
anti-microbial regions 202a including at least one anti-microbial
agent, the one or more selectively actuatable anti-microbial
regions 202a configured to direct at least one anti-microbial agent
to one or more areas of at least one of the outer surface 106 of
the body structure 104, the inner surface 108 of the body structure
104, or embedded in the internal body structure 104; and one or
more sensors 302 configured to detect at least one microbial
component proximate one or more areas of the body structure
104.
[0298] In an embodiment, an insertable device 102 comprises a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; at least one
actively controllable anti-microbial nanostructure 206a projecting
from at least one of the outer surface 106, or the inner surface
108, and at least one sensor 302 configured to detect one or more
microorganisms present proximate the body structure 104.
[0299] In an embodiment, an anti-microbial region 202 is configured
to provide at least one of an energy stimulus 350 (e.g.,
electromagnetic energy stimulus 350a, electrical energy stimulus
350b, acoustic energy stimulus 350c, or thermal energy stimulus
350d). In an embodiment, the plurality of selectively actuatable
anti-microbial regions 202a are configured to deliver at least one
of a spatially collimated energy stimulus 350e; spatially focused
energy stimulus 350f; temporally patterned energy stimulus 350g; or
spaced-apart patterned energy stimulus 350h.
[0300] As shown in FIG. 8, the system 100 can include, among other
things, one or more databases 258. In an embodiment, a database 258
includes spectral information configured a physical data structure
790. In an embodiment, a database 258 includes at least one of
inflammation indication parameter data 776a, infection indication
parameter data 776b, diseased tissue indication parameter data
776c, or the like. In an embodiment, a database 258 includes at
least one of absorption coefficient data 776d, extinction
coefficient data 776e, scattering coefficient data 776f, or the
like. In an embodiment, a database 258 includes at least one of
stored reference data 776g (e.g., infection marker data,
inflammation marker data, infective stress marker data, systemic
inflammatory response syndrome data, sepsis marker data, or the
like).
[0301] In an embodiment, a database 258 includes information
associated with a disease state of a biological subject 222. In an
embodiment, a database 258 includes measurement data. In an
embodiment, a database 258 includes at least one of psychosis state
indication information, psychosis trait indication information, or
predisposition for a psychosis indication information. In an
embodiment, a database 258 includes at least one of infection
indication information, inflammation indication information,
diseased state indication information, or diseased tissue
indication information. In an embodiment, a database 258 includes
at least one of cryptographic protocol information, regulatory
compliance protocol information (e.g., FDA regulatory compliance
protocol information, or the like), regulatory use protocol
information, authentication protocol information, authorization
protocol information, delivery regimen protocol information,
activation protocol information, encryption protocol information,
decryption protocol information, treatment protocol information, or
the like. In an embodiment, a database 258 includes at least one of
energy stimulus control delivery information, energy emitter 220
control information, power control information, anti-microbial
region 202 control information, or the like. In an embodiment, a
database 258 includes at least one spatial or temporal information
associated with anti-microbial region activation, anti-microbial
agent delivery, anti-microbial protruding element actuation, or
other anti-microbial surface property 204 employed.
[0302] In an embodiment, the system 100 is configured to compare an
input associated with at least one characteristic associated with a
biological subject 222 to a database 258 of stored reference
values, and to generate a response 299 based in part on the
comparison. In an embodiment, the system 100 is configured to
compare an input associated with at least one physiological
characteristic associated with a biological subject 222 to a
database 258 of stored reference values, and to generate a response
299 based in part on the comparison.
[0303] In an embodiment, the at least one characteristic associated
with a biological subject 222 includes real-time detected
information associated with a biological sample 808 (e.g., tissue,
biological fluid, infections agent, biomarker, or the like)
proximate an insertable device 102. In an embodiment, the at least
one characteristic associated with a biological subject 222
includes a measurand detected at a plurality of time intervals. In
an embodiment, the at least one characteristic associated with a
biological subject 222 includes real-time detected information
associated with a biological sample 808 (e.g., a biological fluid)
received within one or more fluid-flow passageways 110.
[0304] Referring again to FIG. 3, the system 100 can include, among
other things, a plurality of actuatable anti-microbial regions 202a
that are selectively actuatable between at least a first
anti-microbial state and a second anti-microbial state. For
example, in an embodiment, an insertable device 102 includes a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; and one or more
actuatable anti-microbial regions 202a configured to direct at
least one anti-microbial agent to one or more anti-microbial
regions 202 proximate at least one of the outer surface 106 or
inner surface 108 of the body structure 104. In an embodiment, the
one or more actuatable anti-microbial regions 202a are configured
to alter at least one anti-microbial property 204 in response 299
to detection of at least one microorganism. In an embodiment, the
one or more actuatable anti-microbial regions 202a are selectively
actuatable between at least a first anti-microbial state and a
second anti-microbial state. In an embodiment, a plurality of
actuatable anti-microbial regions 202a are configured to actuate
between the at least first anti-microbial state and the second
anti-microbial state in response 299 to a detected microorganism.
In another example, the anti-microbial nanostructure 206a is
actively controllable. In an embodiment, the at least one actively
controllable anti-microbial nanostructure 206a is configured for
cyclical activation. In an embodiment, the cyclical activation
includes cyclical activation of a spaced-apart distribution or a
temporally patterned distribution. In an embodiment, the at least
one actively controllable anti-microbial nanostructure 206a is
configured for patterned activation (e.g., spatial or temporal
pattern). In an embodiment, the at least one actively controllable
anti-microbial nanostructure 206a is configured to be randomly or
nonrandomly activated. In another example, the system 100 includes
an actively controllable circuit configured to deliver in vivo an
external stimulus to one or more anti-microbial regions 202 of the
body structure 104 for a character and time sufficient to actuate
from the first anti-microbial state to the second anti-microbial
state. In an embodiment, one or more actuatable anti-microbial
regions are configured to actuate at least one of
electrochemically, electromagnetically, photochemically,
acoustically, magnetically, or electro-optically between the first
actuatable state and second actuatable state. In an embodiment, the
one or more actuatable anti-microbial regions 202a are controllably
actuatable between an active state and a passive state. In an
embodiment, the one or more actuatable anti-microbial regions 202a
are controllably actuatable between an active state and a passive
state based at least in part on detected information from one or
more sensors 302. In an embodiment, one or more actuatable
anti-microbial regions 202a are selectively actuatable between at
least one first actuatable state and a second actuatable state via
at least one switch 118.
[0305] With continued reference to FIG. 3, the system 100 can
include, among other things, at least one computing device 230
including one or more processors (e.g., a microprocessors), central
processing units (CPUs) 234, a digital signal processors (DSPs)
236, an application-specific integrated circuits (ASICs) 238, a
field programmable gate arrays (FPGAs) 240, or other controllers
388, or the like, or any combinations thereof, and can include
discrete digital or analog circuit elements or electronics, or
combinations thereof. The system 100 can include, among other
things, one or more field programmable gate arrays having a
plurality of programmable logic components. The system 100 can
include, among other things, one or more an application specific
integrated circuits having a plurality of predefined logic
components.
[0306] In an embodiment, the processor 232 is configured to control
activation or actuation of at least one anti-microbial region 202.
In an embodiment, the processor 232 is configured to be responsive
to at least one sensor 302 of the system 100. In an embodiment the
computing device 230 comprises at least one controller 388. In an
embodiment, at least one computing device 230 is operably coupled
to one or more anti-microbial regions 202. In an embodiment, one or
more of the anti-microbial regions 202 are configured for selective
actuation via one or more computing devices 230. In an embodiment,
the controller 388 is configured to actuate one or more
independently addressable anti-microbial regions 202b. In an
embodiment, the controller 388 is configured to actuate at least
one or more independently addressable anti-microbial regions 202b
in response to detected information from at least one sensor 302.
In an embodiment, the controller 388 is configured to actuate one
or more independently addressable anti-microbial regions 202b in
response to at least one of a scheduled program, external command,
history of a previous presence of a microorganism, expected
presence of microorganisms, expected presence of a particular
microorganism, or history of a previous actuation. In an
embodiment, the system 100 includes actuating means (e.g., switch,
etc.) for concurrently or sequentially actuating two or more of the
plurality of independently addressable anti-microbial regions 202b
determined to have a microorganism present proximate to the
same.
[0307] The system 100 can include, among other things, a plurality
of independently addressable anti-microbial regions 202b. In an
embodiment, the plurality of independently addressable
anti-microbial regions 202b is disposed along a longitudinal axis
of the insertable device 102. In an embodiment, the independently
addressable anti-microbial regions 202b are configured to direct an
anti-microbial property 204 to one or more regions proximate at
least one of the outer surface 106 or the inner surface 108 of the
body structure 104. In an embodiment, the plurality of
independently addressable anti-microbial regions 202b includes at
least one actuatable anti-microbial property 204. In an embodiment,
the system 100 further includes circuitry 602 (as shown in FIG. 6),
configured for determining the presence of at least one
microorganism proximate at least one of a plurality of
independently addressable anti-microbial regions 202b of the body
structure 104. In an embodiment, the at least one actuatable
anti-microbial property 204 is configured to be actuated by at
least one of a program, or the presence of at least one
microorganism.
[0308] In an embodiment, the system 100 includes actuating means
272 for concurrently or sequentially actuating two or more of the
anti-microbial regions 202. In an embodiment, the actuating means
272 includes one or more switches 218. In an embodiment, the one or
more switches 218 are operably coupled to one or more computing
devices 230. In an embodiment, the one or more switches 218 are
configured to increase or decrease the release of at least one
anti-microbial agent from the one or more selectively actuatable
anti-microbial regions 202a.
[0309] In an embodiment, the one or more switches 218 include at
least one acoustically active material 218g. In an embodiment, the
one or more switches 218 include at least one of an
electro-mechanical switch 218a, electrochemical switch 218b,
electrical switch 218c, electro-optic switch 218d, acousto-optic
switch 218e, or optical switch 218f.
[0310] In an embodiment, the actuating means 272 includes at least
one computing device 230 operably coupled to one or more switches
218. In an embodiment, the actuating means 272 includes at least
one optical antifuse. In an embodiment, the actuating means 272
includes a movable component having an optical energy reflecting
substrate. In an embodiment, the movable component is actuated by
an electromagnetic energy stimulus generated by one or more energy
emitters 220, and configured to guide an optical energy along at
least one of the anti-microbial regions 202 when actuated. In an
embodiment, the actuating means 272 is configured to concurrently
or sequentially actuate two or more of the independently
addressable energy or selectively actuatable anti-microbial regions
202a.
[0311] Anti-microbial regions 202 forming part of the insertable
device 102, can take a variety of forms, configurations, and
geometrical patterns including for example, but not limited to, a
one-, two-, or three-dimensional arrays, a pattern 109 comprising
concentric geometrical shapes, a pattern comprising rectangles,
squares, circles, triangles, polygons, any regular or irregular
shapes, or the like, or any combination thereof (as shown in FIGS.
5A and 5B).
[0312] In an embodiment, at least one of the actuatable
anti-microbial regions 202a includes at least one anti-microbial
reservoir 208 actuatable by the presence of at least one
microorganism proximate at least one of the actuatable
anti-microbial regions 202a. In an embodiment, the one or more
actuatable anti-microbial regions 202a are configured to deliver at
least one anti-microbial agent in a spatially patterned
distribution. In an embodiment, the one or more actuatable
anti-microbial regions 202a are configured to deliver at least one
anti-microbial agent in a temporally patterned distribution.
[0313] In an embodiment, the actively controllable anti-microbial
nanostructure 206a is movable. In an embodiment, the movable
anti-microbial nanostructure 206a includes at least one
micro-electromechanical structure. In an embodiment, the movable
anti-microbial nanostructure 206a includes at least one
electroactive polymer. In an embodiment, the movable anti-microbial
nanostructure 206a is configured to deflect one or more
microorganisms. In an embodiment, the movable anti-microbial
nanostructure 206a is configured to extend or contract. In an
embodiment, the movable anti-microbial nanostructure 206a is
configured to increase or decrease the spacing between two or more
nanostructures 206a. In an embodiment, the movable anti-microbial
nanostructure 206a is configured to move in at least one of
rotation, torsion, compression, axial, radial, or lateral
movement.
[0314] In an embodiment, the distance between at least two
anti-microbial nanostructures 206a is less than or equal to about
0.01 .mu.m, about 0.05 .mu.m, about 1.0 .mu.m, about 2.0 .mu.m,
about 3.0 .mu.m, about 4.0 .mu.m, about 5.0 .mu.m, about 6.0 .mu.m,
about 7.0 .mu.m, about 8.0 .mu.m, about 9.0 .mu.m, about 10.0
.mu.m, about 11.0 .mu.m, about 12.0 .mu.m, about 13.0 .mu.m, about
14.0 .mu.m, about 15.0 .mu.m, about 16.0 .mu.m, about 17.0 .mu.m,
about 18.0 .mu.m, about 19.0 about 20.0 .mu.m.
[0315] In an embodiment, the actively controllable anti-microbial
nanostructure 206a includes at least one of silver, copper,
rubidium, platinum, gold, nickel, lead, cobalt, potassium, zinc,
bismuth, tin, cadmium, chromium, aluminum, calcium, mercury,
thallium, gallium, strontium, barium, lithium, magnesium, oxides,
hydroxides, or salts thereof. In an embodiment, the at least one
actively controllable anti-microbial nanostructure 206a includes at
least one of graphene, black silica, hydrogenated diamond,
zirconium, or diamond. In an embodiment, the at least one actively
controllable anti-microbial nanostructure 206a includes at least
one of polyvinyl chloride, polyester, polyethylene, polypropylene,
ethylene, polyolefin, acrylic, polycarbonate, or silicone, or
homopolymers or copolymers thereof. In an embodiment, the at least
one actively controllable anti-microbial nanostructure 206a
includes at least one of polytetrafluoroethylene or
polydimethylsiloxane elastomer.
[0316] In an embodiment, the at least one actively controllable
anti-microbial nanostructure 206a includes a plurality of
nanostructures 206a configured in at least one spatial pattern. In
an embodiment, the at least one spatial or temporal pattern 109
includes at least one of a repeating pattern, non-repeating
pattern, or partially repeating pattern. In an embodiment, the at
least one spatial pattern is derived from information relating to
the type of microorganism expected to be present proximate the body
structure 104.
[0317] In an embodiment, the spacing between at least two, actively
controllable anti-microbial nanostructures 206a includes a space of
at least about 1 .mu.m, at least about 5 .mu.m, at least about 10
.mu.m, at least about 15 .mu.m, at least about 20 .mu.m, at least
about 25 .mu.m, at least about 30 .mu.m, at least about 35 .mu.m,
at least about 40 .mu.m, at least about 45 .mu.m, at least about 50
.mu.m, at least about 55 .mu.m, at least about 60 .mu.m, at least
about 65 .mu.m, at least about 70 .mu.m, at least about 75 .mu.m,
at least about 80 .mu.m, at least about 85 .mu.m, at least about 90
.mu.m, at least about 95 .mu.m, at least about 100 .mu.m, at least
about 110 .mu.m, at least about 120 .mu.m, at least about 130
.mu.m, at least about 150 .mu.m, at least about 160 .mu.m, at least
about 170 .mu.m, at least about 180 .mu.m, at least about 190
.mu.m, at least about 200 .mu.m, or any space therebetween or
greater than.
[0318] In an embodiment, the diameter of the at least one actively
controllable anti-microbial nanostructure 206a is at least about
0.5 nm, at least about 1 nm, at least about 5 nm, at least about 10
nm, at least about 15 nm, at least about 20 nm, at least about 25
nm, at least about 30 nm, at least about 35 nm, at least about 40
nm, at least about 45 nm, at least about 50 nm, at least about 55
nm, at least about 60 nm, at least about 65 nm, at least about 70
nm, at least about 75 nm, at least about 80 nm, at least about 85
nm, at least about 90 nm, at least about 95 nm, at least about 100
nm, at least about 110 nm, at least about 120 nm, at least about
130 nm, at least about 150 nm, at least about 160 nm, at least
about 170 nm, at least about 180 nm, at least about 190 nm, at
least about 200 nm, or any value therebetween or greater.
[0319] In an embodiment, the spacing between components of an
anti-microbial region 202 is such that a single microorganism can
fit (or complete an electrical circuit) therein.
[0320] In an embodiment, the depth of the at least one actively
controllable anti-microbial nanostructure 206a is at least about
0.25 .mu.m, at least about 0.5 .mu.m, at least about 1 .mu.m, at
least about 5 .mu.m, at least about 10 .mu.m, at least about 15
.mu.m, at least about 20 .mu.m, at least about 25 .mu.m, at least
about 30 .mu.m, at least about 35 .mu.m, at least about 40 .mu.m,
at least about 45 .mu.m, at least about 50 .mu.m, at least about 55
.mu.m, at least about 60 .mu.m, at least about 65 .mu.m, at least
about 70 .mu.m, at least about 75 .mu.m, at least about 80 .mu.m,
at least about 85 .mu.m, at least about 90 .mu.m, at least about 95
.mu.m, at least about 100 .mu.m, at least about 110 .mu.m, at least
about 120 .mu.m, at least about 130 .mu.m, at least about 150
.mu.m, at least about 160 .mu.m, at least about 170 .mu.m, at least
about 180 .mu.m, at least about 190 .mu.m, at least about 200
.mu.m, or any value therebetween or greater.
[0321] In an embodiment, the actively controllable anti-microbial
nanostructure 206a includes at least one electrically actuatable
contact. In an embodiment, the actively controllable anti-microbial
nanostructure 206a includes at least two electrically actuatable
contacts. In an embodiment, the at least two electrically
actuatable contacts are differentially chargeable. In an
embodiment, the at least two electrically actuatable contacts are
arranged in a static charge pattern. In an embodiment, the at least
two electrically actuatable contacts are arranged in a dynamic
charge pattern. In an embodiment, the at least one electrically
actuatable contact can be locally charged based on detection of at
least one microbe present proximate the at least one electrically
actuatable contact. In an embodiment, the at least two electrically
actuatable contacts are spaced such that the presence of a microbe
conducts current via the at least two electrically actuatable
contacts. In an embodiment, the at least one anti-microbial
nanostructure 206a includes at least one photoactive material. In
an embodiment, the photoactive material includes at least one
photocatalyst. In an embodiment, the photoactive material includes
titanium dioxide.
[0322] In an embodiment, the plurality of actuatable anti-microbial
regions 202a are actively controllable, via one or more computing
device 230, between the at least first anti-microbial state and the
second anti-microbial state.
[0323] The system 100 can include, among other things, one or more
actively controllable reflective or transmissive components
configured to outwardly transmit or internally reflect an energy
stimulus propagated therethrough. In an embodiment, an insertable
device 102 includes one or more actively controllable reflective or
transmissive components configured to outwardly transmit or
internally reflect an energy stimulus propagated therethrough.
[0324] In an embodiment, one or more actuatable anti-microbial
regions 202a are selectively actuatable between at least a first
transmissive state and a second transmissive state via at least one
acoustically active material. In an embodiment, one or more of
plurality of actuatable anti-microbial regions 202a are selectively
actuatable between at least a first transmissive state and a second
transmissive state via at least one electro-mechanical switch. In
an embodiment, one or more of plurality of actuatable
anti-microbial regions 202a are selectively actuatable between at
least a first transmissive state and a second transmissive state
via at least one electro-optic switch. In an embodiment, one or
more of the actuatable anti-microbial regions 202a are selectively
actuatable between at least a first transmissive state and a second
transmissive state via at least one acousto-optic switch. In an
embodiment, one or more of the actuatable anti-microbial regions
202a are selectively actuatable between at least a first
transmissive state and a second transmissive state via at least one
optical switch.
[0325] The system 100 can include, among other things, a computing
device 230 operably coupled to one or more of the actuatable
anti-microbial regions 202a. In an embodiment, the controller 388
is configured to cause a change between an at least first
anti-microbial state and a second anti-microbial state based on
detected information from the one or more sensors 302. In an
embodiment, the controller 388 is programmable.
[0326] In an embodiment, the insertable device 102 includes one or
more computing devices 230 operably coupled to one or more of the
actuatable anti-microbial regions 202a. In an embodiment, at least
one of the computing devices 230 is configured to cause a change
between the at least a first anti-microbial state and a second
anti-microbial state based on detected information from the one or
more sensors 302. In an embodiment, at least one computing device
230 is configured to actuate one or more of the actuatable
anti-microbial regions 202a between the at least first
anti-microbial state and the second anti-microbial state based on a
comparison of a detected characteristic associated with the
biological sample 808 proximate at least one of the outer surface
106 or the inner surface 108 of the body structure 104. For
example, in an embodiment, the one or more sensors 302 are
configured to detect at least one characteristic associated with
one or more anti-microbial regions 202 proximate at least one of
the outer surface 106 or the inner surface 108 of the body
structure 104; and at least one controller 388 operably coupled to
one or more of the spaced-apart release ports 118a and configured
to actuate one or more of the spaced-apart release ports 118a
between an anti-microbial agent discharge state and an
anti-microbial agent retention state based on a comparison of a
detected characteristic to stored reference data.
[0327] For example, in an embodiment the anti-microbial region 202
affects adhesion of, for example, bacteria, or other
microorganisms, and biofilm formation by changing at least one of a
functional, structural, and chemical characteristic of a surface on
an insertable device 102. For example, adhesion may be affected by
changing surface morphology. It may also be possible to modulate
the adhesion and biofilm formation by modulating at least one of
the functional, structural, or chemical characteristics of a
surface on an insertable device 102. By modulating at least one of
a functional, structural, or chemical characteristic of a surface
on an insertable device 102, the transport properties of a fluid
exposed to the surface on an insertable device 102 may also be
affected.
[0328] In an embodiment, at least one of the fluid-flow passageways
110 includes one or more surface anti-microbial regions that are
energetically actuatable between a substantially hydrophobic state
and a substantially hydrophilic state. In an embodiment, the one or
more fluid-flow passageways 110 includes a surface region that is
energetically actuatable between at least a first hydrophilic state
and a second hydrophilic state. In an embodiment, at least one of
the fluid-flow passageways 110 includes a surface region that is
energetically actuatable between a hydrophobic state and a
hydrophilic state. In an embodiment, at least one of the fluid-flow
passageways 110 includes a surface region having a material that is
switchable between a zwitterionic state and a non-zwitterionic
state.
[0329] In an embodiment, the one or more fluid-flow passageways 110
includes at least one of an anti-microbial coating. In an
embodiment, at least one of the fluid-flow passageways 110 includes
an anti-microbial coating. In an embodiment, at least one of the
fluid-flow passageways 110 includes a surface region that is
energetically actuatable between an anti-microbial state. In an
embodiment, at least one anti-microbial coating is configured for
time-release of at least one anti-microbial agent. In an
embodiment, the coating includes at least one of an anti-microbial
agent, electroactive polymer, petroleum jelly, silver gel,
surfactant, alcohol gel, or other coating. In an embodiment, the
coating includes at least one expandable material. In an embodiment
the expandable material is actively controllable. In an embodiment,
the expandable material is configured to physically dislocate at
least one microorganism on at least one of the inner surface 108 or
outer surface 106 of the body structure 104. In an embodiment, the
at least one expandable material is configured to expand in at
least one longitudinal or transverse motion.
[0330] In an embodiment, an insertable device 102 includes a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; one or more
anti-microbial regions 202 including at least one anti-microbial
coating actuatable by the presence of at least one microorganism,
and configured to actively elute at least one anti-microbial agent
proximate to at least one of the outer surface 106 or the inner
surface 108 of the body structure 104.
[0331] In an embodiment, an insertable device 102 includes a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; one or more
anti-microbial regions 202 including at least one anti-microbial
reservoir 208 including at least one anti-microbial agent, the at
least one anti-microbial reservoir 208 configured to deliver at
least one anti-microbial agent proximate to at least one of the
outer surface 106 or the inner surface 108 of the body structure
104.
[0332] In an embodiment, the body structure 104 includes one or
more anti-microbial protruding elements 206 (e.g., nanostructure,
microstructure, nanoscale pillar, nanoscale ridge, high aspect
ratio nanofibrillar structure, nanoscale projection, nanoscale
irregularity, nanoscale elongation, nanoscale valley, nanoscale
trough, nanoscale spike (e.g., blunt tip spike, sharp tip spike,
etc.), or the like) on at least one surface. In an embodiment, the
at least one anti-microbial nanostructure 206a includes at least
one surface portion that is energetically unstable. In an
embodiment, the at least one anti-microbial nanostructure 206a
includes at least a portion of a surface that is hydrophilic. In an
embodiment, the at least one anti-microbial nanostructure 206a
includes at least a portion of a surface that is hydrophobic.
[0333] In an embodiment, the anti-microbial protruding element 206
is produced by femtosecond laser pulses against a substrate. In an
embodiment, the substrate includes at least one of a hydrophobic,
superhydrophobic, or ultrahydrophobic substrate. In an embodiment,
the substrate includes one or more of a metal, ceramic, glass,
non-crystalline material, semiconductor, composite, or polymer. In
an embodiment, the polymer includes a diarylethene. In an
embodiment, the polymer includes at least one electrically
conductive polymer. In an embodiment, the at least one electrically
conductive polymer includes at least one dopant. In an embodiment,
the at least one dopant includes at least one low surface energy
dopant. In an embodiment, the at least one dopant includes
perfluorooctanesulfonate. In an embodiment, the at least one
electrically conductive polymer includes the at least one
electrically conductive polymer includes at least one of
polythiophene, poly(p-phenylene), poly(aniline), polyacetylene,
poly(pyrrole), poly(N-methylpyrrole), poly(thiophene), poly(alkyl
thiophene), poly(furan), poly(pyridine), poly(fluorene),
poly(3-hexylthiophene), polynaphthalene, poly(p-phenylene sulfide),
poly(azulene), polyacene, polyquinone, polystyrene sulfonate,
polyethylenedioxythiophene, poly(p-phenylene), poly(p-phenylene
vinylene), polysulfone, poly(pyridine), poly(quinoxaline),
polyanthraquinone, poly(n-vinylcarbazole), poly(acene), or
poly(heteroaromatic vinylene).
[0334] In an embodiment, the liquid-solid contact angle of the
substrate is greater than about 0 degrees, greater than about 5
degrees, greater than about 10 degrees, greater than about 20
degrees, greater than about 30 degrees, greater than about 40
degrees, greater than about 50 degrees, greater than about 60
degrees, greater than about 70 degrees, greater than about 80
degrees, greater than about 90 degrees, greater than about 100
degrees, greater than about 105 degrees, greater than about 110
degrees, greater than about 120 degrees, greater than about 130
degrees, greater than about 140 degrees, greater than about 150
degrees, greater than about 160 degrees, greater than about 170
degrees, about 180 degrees, or any value therebetween.
[0335] In an embodiment, a plurality of nanostructures 206a
includes at least two nanostructures 206a oriented parallel to each
other. In an embodiment, a plurality of nanostructures 206a
includes at least two nanostructures 206a oriented perpendicular to
each other. In an embodiment, a plurality of nanostructures 206a
includes at least two nanostructures 206a with at least one
topographical pattern. In an embodiment, the plurality of
anti-microbial nanostructures 206a includes at least two different
anti-microbial nanostructures 206a. In an embodiment, the at least
two different anti-microbial nanostructures 206a include at least
one different spatial property or temporal property (e.g.
wettability).
[0336] The wettability, or other surface properties can be
controlled by altering the density of the protruding elements. See
e.g., Spori et al., Cassie-State Wetting Investigated by Means of a
Hole-to-Pillar Density Gradient, Langmuir, 2010, 26 (12), pp
9465-9473. In an embodiment, the anti-microbial nanostructure 206a
is actuatable. In an embodiment, the at least one anti-microbial
nanostructure 206a includes at least one of a rough surface or
patterned surface. In an embodiment, the rough surface includes an
engineered roughness index of from about 1 to about 100, wherein
the roughness index includes the ratio of the actual surface area
to the geometric surface area. In an embodiment, the at least one
anti-microbial nanostructure 206a is configured to be actuated by
at least partial degradation of at least one component of the body
structure 104.
[0337] In an embodiment, the at least one anti-microbial
nanostructure 206a is configured to modulate at least one of
microbial movement, microbial attachment, microbial growth, or
microbial persistence proximate at least one surface of the body
structure 104. In an embodiment, the at least one anti-microbial
nanostructure 206a is configured to increase at least one of
microbial movement, microbial attachment, microbial growth, or
microbial persistence proximate at least one surface of the body
structure 104. In an embodiment, the at least one anti-microbial
nanostructure 206a is configured to decrease at least one of
microbial movement, microbial attachment, microbial growth, or
microbial persistence proximate at least one surface of the body
structure 104.
[0338] In an embodiment, the insertable device 102 includes at
least one switchable surface 404. In an embodiment, the switchable
surface 404 is configured to alter the liquid-solid contact angle
of the at least one actuatable anti-microbial nanostructure 206a.
In an embodiment, the at least one switchable surface 404 includes
poly(dimethylsiloxane). In an embodiment, the switchable surface
404 is reversibly switchable. In an embodiment, the switchable
surface 404 is configured to alter at least one of the electrical
charge, chemical composition, polarizability, transparency,
conductivity, light absorption, osmotic potential, zeta potential,
surface energy, coefficient of friction, or affinity for at least
one microbial component. In an embodiment, the at least one
switchable surface 404 is configured to switch from a first
conformation state to a second conformation state in response 299
to an external stimulus. In an embodiment, the at least one
switchable surface 404 is switchable from a first state to a second
state. In an embodiment, the second state inhibits anti-microbial
presence proximate at least one surface of the insertable device
102.
[0339] In an embodiment, the external stimulus includes at least
one microorganism. In an embodiment, the external stimulus includes
at least one physical or chemical change proximate the switchable
surface 404. In an embodiment, the at least one external stimulus
includes at least one of a change in applied voltage, change in
temperature, change in pH, exposure to ultraviolet light,
disruption to ultraviolet light, electromagnetic radiation,
magnetic field, removal of a magnetic field, change in capacitance,
change in electrostatic charge, removal of electrostatic charge,
exposure to a ligand, exposure to a solvent, or exposure to an ion.
In an embodiment, the first conformation state and the second
conformation state differ in degree of hydrophobicity. In an
embodiment, the second conformation state has a greater
liquid-solid contact angle than the first conformation state.
[0340] In an embodiment, the at least one anti-microbial
nanostructure 206a is configured to be activated by at least one
physical or chemical change on the switchable surface 404. In an
embodiment, the at least one anti-microbial nanostructure 206a is
configured to be activated by at least one of a change in applied
voltage, change in temperature, change in pH, exposure to
ultraviolet light, disruption to ultraviolet light, electromagnetic
radiation, magnetic field, removal of a magnetic field, change in
capacitance, change in electrostatic charge, removal of
electrostatic charge, exposure to a ligand, exposure to a solvent,
or exposure to an ion. In an embodiment, the first conformation
state and the second conformation state differ in degree of
hydrophobicity. In an embodiment, the second conformation state has
a greater liquid-solid contact angle than the first conformation
state.
[0341] In an embodiment, the insertable device 102 includes at
least one photonic crystal. In an embodiment, the photonic crystal
includes at least one biopolymer. In an embodiment, the photonic
crystal includes at least one nanopatterned surface. In an
embodiment, the at least one photonic crystal includes at least one
embedded material. In an embodiment, the at least one embedded
material includes at least one of a biological cell, enzyme,
nucleic acid, detection material, small molecule, protein, peptide,
polypeptide, amino acid, carbohydrate, lipid, therapeutic agent,
electronic component, or other material. In an embodiment, the at
least one detection material includes at least one of a contrast
agent, or electronic identification device. In an embodiment, the
at least one detection material includes at least one of a
radioactive substance, luminescent substance, or odorous substance.
In an embodiment, the detection material includes at least one of a
diamagnetic particle, ferromagnetic particle, paramagnetic
particle, super paramagnetic particle, particle with altered
isotope, or other magnetic particle.
[0342] For example, in an embodiment, an insertable device 102
comprises a body structure 104 having an outer surface 106 and an
inner surface 108 defining one or more fluid-flow passageways 110;
wherein at least one of the outer surface 106 or the inner surface
108 of the body structure 104 includes at least one anti-microbial
nanostructure 206a. In an embodiment, an insertable device 102
comprises a body structure 104 including at least one
anti-microbial nanostructure 206a. In an embodiment, an insertable
device 102 comprises a body structure 104 having an outer surface
106 and an inner surface 108 defining one or more fluid-flow
passageways 110; wherein at least one of the outer surface 106, or
the inner surface 108 of the body structure 104 includes at least
one actuatable anti-microbial nanostructure 206a. In an embodiment,
an insertable device 102 comprises a body structure 104 including
at least one actuatable anti-microbial nanostructure 206a.
[0343] In an embodiment, the one or more anti-microbial regions 202
are configured to photochemically actuate between the first
wettability state and the second wettability state in the presence
of an ultraviolent energy. In an embodiment, the one or more
anti-microbial regions 202 are configured to actuate between the
first wettability state and the second wettability state in the
presence of an applied potential. In an embodiment, the one or more
anti-microbial regions 202 are UV-manipulatable between the first
wettability and the second wettability.
[0344] In an embodiment, the one or more anti-microbial regions 202
are configured to photochemically actuate between a substantially
hydrophobic state and a substantially hydrophilic state. In an
embodiment, the one or more anti-microbial regions 202 are
configured to electrically actuate between a substantially
hydrophobic state and a substantially hydrophilic state. In an
embodiment, the one or more anti-microbial regions 202 include at
least one ZnO nano-rod film, coating, or material that is
UV-manipulatable between a superhydrophobic state and
superhydrophilic state.
[0345] In an embodiment, the one or more anti-microbial regions 202
are energetically controllably actuatable between a substantially
hydrophobic state and a substantially hydrophilic state. In an
embodiment, the one or more anti-microbial regions 202 are
energetically controllably actuatable between at least a first
hydrophilic state and a second hydrophilic state. In an embodiment,
the one or more anti-microbial regions 202 are energetically
controllably actuatable between a hydrophobic state and a
hydrophilic state. In an embodiment, the one or more anti-microbial
regions 202 include a material that is switchable between a
zwitterionic state and a non-zwitterionic state.
[0346] Controllable-wettability-components 804 can be made using a
variety of methodologies and technologies including, for example,
spray pyrolysis, electro-deposition, electro-deposition onto
laser-drilled polymer molds, laser cutting and electro-polishing,
laser micromachining, photolithography, surface micro-machining,
soft lithography, x-ray lithography, LIGA techniques (e.g., X-ray
lithography, electroplating, and molding), conductive paint silk
screen techniques, conventional pattering techniques, injection
molding, conventional silicon-based fabrication methods (e.g.,
inductively coupled plasma etching, wet etching, isotropic and
anisotropic etching, isotropic silicon etching, anisotropic silicon
etching, anisotropic GaAs etching, deep reactive ion etching,
silicon isotropic etching, silicon bulk micromachining, or the
like), complementary-symmetry/metal-oxide semiconductor (CMOS)
technology, deep x-ray exposure techniques, and the like. Further
examples of methodologies and technologies for making controllable
wettability components can found in the following documents (the
contents of each of which is incorporated herein by reference):
Feng et al., Reversible Super-hydrophobicity to
Super-hydrophilicity Transition of Aligned ZnO Nanorod Films, J.
Am. Chem. Soc., 126, 62-63 (2004), Lin et al., Electrically Tunable
Wettability of Liquid Crystal/Polymer Composite Films, Optics
Express 16(22): 17591-598 (2008), Spori et al., Cassie-State
Wetting Investigated by Means of a Hole-to-Pillar Density Gradient,
Langmuir, 2010, 26 (12), pp 9465-9473 Wang et al., Photoresponsive
Surfaces with Controllable Wettability, Journal of Photochemistry
and Photobiology C: Photochemistry Reviews, 8(1): 18-29 (2007),
U.S. Pat. No. 6,914,279 (issued Jul. 5, 2005), and U.S. Patent
Publication No. 2008/0223717 (published Sep. 18, 2008).
[0347] The wettability of a substrate can be determined using
various technologies and methodologies including contact angle
methods, the Goniometer method, the Whilemy method, the Sessile
drop technique, or the like. Wetting is a process by which a liquid
interacts with a solid. Wettability (the degree of wetting) is
determined by a force balance between adhesive and cohesive force
and is often characterized by a contact angle. The contact angle is
the angle made by the intersection of the liquid/solid interface
and the liquid/air interface. Alternatively, it is the angle
between a solid sample's surface and the tangent of a droplet's
ovate shape at the edge of the droplet. Contact angle measurements
provide a measure of interfacial energies and conveys direct
information regarding how hydrophilic or hydrophobic a surface is.
For example, superhydrophilic surfaces have contact angles less
than about 5.degree., hydrophilic surfaces have contact angles less
than about 90.degree., hydrophobic surfaces have contact angles
greater than about 90.degree., and superhydrophobic surfaces have
contact angles greater than about 150.degree..
[0348] In an embodiment, the insertable device 102 includes a body
structure 104 including one or more
controllable-wettability-components 804 having switchable wetting
properties. In an embodiment, the insertable device 102 includes a
body structure 104 including one or more
controllable-wettability-components 804 that are energetically
actuatable between at least a first wettability and a second
wettability. In an embodiment, the one or more
controllable-wettability-components 804 are acoustically,
chemically, electro-chemically, electrically, optically, thermally,
or photo-chemically actuatable between at least a first wettability
and a second wettability.
[0349] In an embodiment, the one or more
controllable-wettability-components 804 include at least one
acousto-responsive material.
[0350] In an embodiment, the one or more
controllable-wettability-components 804 include at least one
photo-responsive material. Non-limiting examples of
photo-responsive materials include SnO, SnO.sub.2, TiO.sub.2,
W.sub.2O.sub.3, ZnO, ZnO, and the like. In an embodiment, the one
or more controllable-wettability-components 804 include at least
one film, coating, or material including SnO, SnO.sub.2, TiO.sub.2,
W.sub.2O.sub.3, ZnO, ZnO, or the like. In an embodiment, the one or
more controllable-wettability-components 804 are UV-manipulatable
between at least a first wettability and a second wettability. In
an embodiment, the one or more controllable-wettability-components
804 include one or more ZnO nano-rod films, coatings, or materials
that are UV-manipulatable between a superhydrophobic state and
superhydrophilic state. In an embodiment, the one or more
controllable-wettability-components 804 include at least one
electrochemically active material. Non-limiting examples of
electrochemically active materials include electrochemically active
polymers (e.g., polyaniline, polyethylenethioxythiophene,
conjugated polymer poly(3-hexylthiophene), or the like), and the
like.
[0351] In an embodiment, the one or more
controllable-wettability-components 804 include one or more
superhydrophobic conducting polypyrrole films, coatings, or
components that are electrically switchable between an oxidized
state and a neutral state, resulting in reversibly switchable
superhydrophobic and superhydrophilic properties. (See, e.g.,
Lahann et al., A Reversibly Switching Surface, 299 (5605): 371-374
(2003) 21:47-51 (2003), the contents of each of which is
incorporated herein by reference). In an embodiment, the one or
more controllable-wettability-components 804 include one or more
electrically isolatable fluid-support structures. See, e.g., U.S.
Pat. No. 7,535,692 (issued May 19, 2009), the contents of each of
which is incorporated herein by reference).
[0352] In an embodiment, the one or more
controllable-wettability-components 804 include a plurality of
volume-tunable nanostructures 206a. See, e.g., U.S. Patent
Publication No. 2008/0095977 (published Apr. 24, 2008), the
contents of each of which is incorporated herein by reference). In
an embodiment, the one or more controllable-wettability-components
804 include one or more tunable (electrically tunable)
superhydrophobic conducting polypyrrole films, coatings, or
components. See, e.g., Krupenki et al, Electrically Tunable
Superhydrophobic Nanostructured Surfaces, Bell Labs Technical
Journal 10 (3): 161-170 (2009), the contents of each of which is
incorporated herein by reference). In an embodiment, the one or
more controllable-wettability-components 804 include one or more
electrically tunable crystal/polymer composites. In an embodiment,
the one or more controllable-wettability-components 804 include a
switchable surface 404. See e.g., Gras et al., Intelligent Control
of Surface Hydrophobicity, ChemPhysChem 8(14): 2036-2050
(2007).
[0353] In an embodiment, the insertable device 102 includes one or
more coatings (e.g., optically active coatings, reflective coating,
opaque coatings, transmissive coatings, etc.). In an embodiment, at
least a portion of the body structure 104 includes a surface having
a coating, coatings configured to treat or reduce the concentration
of an infectious agent in the immediate vicinity of the insertable
device 102.
[0354] Non-limiting examples of coatings include anti-biofilm
activity coatings, coatings having self-cleaning properties,
coatings having self-cleaning or anti-bacterial activity, and the
like.
[0355] Further non-limiting examples coatings include polymeric
compositions that resist bacterial adhesion, antimicrobial
coatings, coatings that controllably release antimicrobial agents,
quaternary ammonium silane coatings, chitosan coatings, and the
like. Further non-limiting examples of coatings may be found in,
for example, the following documents (the contents of each of which
is incorporated herein by reference): U.S. Pat. Nos. 7,348,021
(issued Mar. 25, 2008), 7,217,425 (issued May 15, 2007), 7,151,139
(issued Dec. 19, 2006), and 7,143,709 (issued Dec. 5, 2006). In an
embodiment, at least a portion of an inner or an outer surface of
the insertable device 102 includes one or more self-cleaning
coating materials. Non limiting examples of self-cleaning coating
(e.g., Lotus Effect) materials include superhydrophobic materials,
carbon nanotubes with nanoscopic paraffin coating, or the like.
Further non-limiting examples of self-cleaning (e.g., non fouling)
coating materials include antimicrobial, and nonfouling
zwitterionic polymers, zwitterionic surface forming materials,
zwitterionic Polymers, poly(carboxybetaine methacrylate) (pCBMA),
poly(carboxybetaine acrylic amide) (pCBAA), poly(oligo(ethylene
glycol) methyl ether methacrylate) (pOEGMA),
poly(N,N-dimethyl-N-(ethoxycarbonylmethyl)-N-[2'-(methacryloylo-
xy)ethyl]-ammonium bromide), cationic pC8NMA, switchable pCBMA-1
C2, pCBMA-2, and the like. See, e.g., WO 2008/083390 (published
Jul. 10, 2008) (the contents of each of which is incorporated
herein by reference).
[0356] Further non-limiting examples of coatings include
superhydrophobic conducting polypyrrole coatings that are
electrically switchable between an oxidized state and a neutral
state, resulting in reversibly switchable superhydrophobic and
superhydrophilic properties (see, e.g., Lahann et al., A Reversibly
Switching Surface, 299 (5605): 371-374 (2003) 21:47-51 (2003), the
contents of each of which is incorporated herein by reference);
coatings including electrically isolatable fluid-support structures
(see, e.g., U.S. Pat. No. 7,535,692 (issued May 19, 2009), the
contents of each of which is incorporated herein by reference);
coatings including a plurality of volume-tunnable nanostructures
(see, e.g., U.S. Patent Publication No. 2008/0095977 (published
Apr. 24, 2008), the contents of each of which is incorporated
herein by reference); coatings including re-entrant surface
structures (see, e.g., Tuteja et al., Robust Omniphobic Surfaces,
Epub 2008 Nov. 10, 105(47):18200-5 (2008), the contents of each of
which is incorporated herein by reference); coatings including
superhydrophobic conducting polypyrrole materials, coatings
including zwitterionic polymers (see, e.g., Cheng et al., A
Switchable Biocompatible Polymer Surface with Self-Sterilizing and
Nonfouling Capabilities, Angew. Chem. Int. Ed. 8831-8834 (2008),
the contents of each of which is incorporated herein by reference);
or the like.
[0357] Further non-limiting examples of coating include reflective
coatings, beam-splitter coatings, broadband multilayer coatings,
composite coatings, dielectric coatings, dielectric reflective
coatings (e.g., dielectric high reflective coatings), grating
waveguide coatings (e.g., high reflectivity grating waveguide
coatings), IR reflective coatings, metallic reflective coatings
(e.g., metallic high reflective coatings), multilayer coatings,
narrow or broad band coatings, optical coatings, partial reflective
coatings, polymeric coatings, single layer coatings, UV reflective
coatings, UV-IR reflective coatings, and the like, and combinations
thereof. For example, in an embodiment, the insertable device 102
includes at least one of an outer internally reflective or an inner
internally reflective coating on the body structure 104. For
example, in an embodiment, at least a portion of an inner surface
108 or an outer surface 106 of the insertable device 102 includes a
coating configured to internally reflect at least a portion of an
emitted energy stimulus within an interior of at least one of the
fluid-flow passageways 110. In an embodiment, at least a portion of
the body structure 104 includes at least one of an outer internally
reflective coating and an inner internally reflective coating.
[0358] The system 100 can include, among other things, one or more
reflective materials. In an embodiment, the insertable device 102
includes a reflective material. For example, in an embodiment, at
least a portion of the body structure 104 includes a reflective
material. Non limiting examples of reflective materials include
aluminum, aluminum oxide, barium sulfate, chromium, copper,
fluorine, germanium, gold, hafnium dioxide, high refractive index
materials, low refractive index materials, magnesium fluoride,
nickel, nickel-chromium platinum, quartz, rhodium, sapphire,
silicon dioxide, silver, tantalum pentoxide, thorium fluorides,
titanium, titanium dioxide, titanium oxide, tungsten, yttrium
oxide, zinc oxide, zinc sulfide, zirconium, zirconium oxide, and
the like, as well as compounds, composites, and mixtures
thereof.
[0359] For example, in an embodiment, at least a portion of the
insertable device 102 includes one or more coatings including at
least one reflective material. In an embodiment, the reflective
material includes at least one of aluminum, barium sulfate, gold,
silver, titanium dioxide, and zinc oxide. In an embodiment, the
reflective material includes an ultraviolet energy reflective
material. In an embodiment, the ultraviolet energy reflective
material comprises a metallic film. In an embodiment, the
ultraviolet energy reflective material comprises enhanced aluminum.
In an embodiment, the ultraviolet energy reflective material
comprises enhanced aluminum overcoated with at least one of
magnesium fluoride, silicon dioxide, or silicon monoxide. In an
embodiment, the ultraviolet energy reflective material comprises
enhanced aluminum overcoated with high phosphorous nickel. In an
embodiment, the ultraviolet energy reflective material comprises
barium sulfate.
[0360] In an embodiment, at least a portion of the body structure
104 includes an optical material that permits the transmission of
at least a portion of an emitted energy stimulus from an interior
of at least one of the fluid-flow passageways 110 to an exterior of
at least one of the fluid-flow passageways 110. In an embodiment,
at least a portion of the body structure 104 includes an optical
material that internally reflects at least a portion of an emitted
energy stimulus present within an interior of at least one of the
fluid-flow passageways 110. In an embodiment, at least a portion of
the body structure 104 includes an optical material that internally
reflects at least a portion of an emitted energy stimulus within an
interior of at least one of the fluid-flow passageways 110, without
substantially permitting the transmission of the emitted energy
stimulus through an exterior of the body structure 104. In an
embodiment, at least a portion of the body structure 104 includes
an optical material that internally directs at least a portion of
an emitted energy stimulus along a substantially longitudinal
direction of at least one of the fluid-flow passageways 110. In an
embodiment, wherein at least a portion of the body structure 104
includes an optical material that internally directs at least a
portion of an emitted energy stimulus along a substantially lateral
direction of at least one of the fluid-flow passageways 110.
[0361] In an embodiment, an insertable device 102 comprises a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; at least one
actuatable anti-microbial region 202a including at least one
anti-microbial reservoir 208 including at least one anti-microbial
agent, the at least one actuatable anti-microbial reservoir 208
actuatable by the presence of at least one microorganism and
configured to actively elute at least one anti-microbial agent
proximate to at least one of the outer surface 106 or the inner
surface 108 of the body structure 104.
[0362] In an embodiment, an insertable device 102 comprises a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; one or more
anti-microbial regions 202 of the body structure 104 including at
least one anti-microbial agent reservoir 208, the reservoir 208
configured to release one or more anti-microbial agents to the one
or more anti-microbial regions 202 of the body structure 104. In an
embodiment, a system 100 comprises an insertable device 102
including a body structure 104 having an outer surface 106 and an
inner surface 108 defining one or more fluid-flow passageways 110;
and one or more anti-microbial regions 202 proximate at least one
of an outer surface 106, an inner surface 108, or embedded in the
internal body structure 104; the body structure 104 including at
least one anti-microbial agent reservoir 208 operably coupled to
the one or more anti-microbial regions 202; and circuitry 604
configured for operating the at least one anti-microbial agent
reservoir 208.
[0363] In an embodiment, the system 100 comprises circuitry 605
configured for operating at least one sensor 302 operably coupled
to at least one of the anti-microbial regions 202. In an
embodiment, the system 100 comprises circuitry 605 configured for
operating at least one sensor 302 operably coupled to at least one
of the at least one anti-microbial agent reservoir 208. In an
embodiment, the at least one sensor 302 is configured to detect
information related to at least one microbial component. In an
embodiment, the system 100 further comprises circuitry 606
configured for operating one or more central processing units
234.
[0364] In an embodiment, a system 100 includes means for operating
an insertable device 102, the insertable device 102 including a
body structure 104 having an outer surface 106 and an inner surface
108 defining one or more fluid-flow passageways 110; and one or
more anti-microbial regions 202 proximate at least one of an outer
surface 106, an inner surface 108 or embedded in the internal body
structure 104; the body structure 104 including at least one
anti-microbial agent reservoir 208 operably coupled to the one or
more anti-microbial regions 202; and means 604 (as shown in FIG. 7)
for operating the at least one anti-microbial agent reservoir 208.
In an embodiment, the system 100 further comprises means 605 for
operating one or more sensor transmitters 445 or sensor receivers
444.
[0365] In an embodiment, the system 100 includes one or more
computing devices 230 operably coupled to one or more sensors 302.
In an embodiment, at least one computing device 230 is configured
to process an output associated with one or more sensors 302. In an
embodiment, the system 100 includes one or more computing devices
230 configured to concurrently or sequentially operate multiple
sensors 302. In an embodiment, the system 100 is configured to
compare an input associated with at least one characteristic
associated with a biological sample proximate an insertable device
102 to a data structure 260 including reference values, and to
generate a response 299 based in part on the comparison. In an
embodiment, the system 100 is configured to compare an input
associated with at least one physiological characteristic
associated with a biological subject 222 to a data structure 260
including reference values, and to generate a response 299 based in
part on the comparison. In an embodiment, the system 100 is
configured to compare an input associated with at least one
characteristic associated with a biological sample 808 proximate an
insertable device 102 to a data structure 260 including reference
values, and to generate a response 299 based in part on the
comparison.
[0366] In an embodiment, at least one computing device 230 is
configured to perform a comparison of at least one detected
characteristic to stored reference data, and to generate a response
299 based at least in part on the comparison. For example, in an
embodiment, at least one computing device 230 is configured to
perform a comparison of at least one characteristic associated with
the biological sample 808 to stored reference data, and to initiate
a treatment protocol based at least in part on the comparison. In
an embodiment, at least one computing device 230 is configured to
perform a comparison of a detected at least one of the emitted
optical energy or the remitted optical energy from the region
proximate the body structure 104 to reference spectral information,
and to cause an emission of an energy stimulus from one or more
energy emitters 220 to at least one of the outer surface 106 and
the inner surface 108 of the body structure 104. In an embodiment,
one or more computing devices 230 are communicatively coupled to
one or more sensors 302 and configured to actuate a determination
of the at least one characteristic associated with a biological
specimen proximate a surface of the insertable device 102.
[0367] In an embodiment, a computing device 230 is configured to
compare a measurand associated with the biological subject 222 to a
threshold value associated with a tissue spectral model and to
generate a response 299 based on the comparison. In an embodiment,
a computing device 230 is configured to compare an input associated
with at least one characteristic associated with, for example, a
biological sample proximate an insertable device 102 to a database
258 of stored reference values, and to generate a response 299
based in part on the comparison.
[0368] The response 299 can include, among other things, at least
one of a response signal, an absorption parameter, an extinction
parameter, a scattering parameter, a comparison code, a comparison
plot, a diagnostic code, a treatment code, an alarm response, and a
test code based on the comparison of a detected optical energy
absorption profile to characteristic spectral signature
information. In an embodiment, the response 299 includes at least
one of a display, a visual representation (e.g., a visual depiction
representative of the detected (e.g., assessed, calculated,
evaluated, determined, gauged, measured, monitored, quantified,
resolved, sensed, or the like) information) component, a visual
display of at least one spectral parameter, and the like. In an
embodiment, the response 299 includes a visual representation
indicative of a parameter associated with an infection present in a
region of a biological sample proximate one or more sensors 302. In
an embodiment, the response 299 includes a generating a
representation (e.g., depiction, rendering, modeling, or the like)
of at least one physical parameter associated with a biological
specimen.
[0369] In an embodiment, at least one computing device 230 is
configured to perform a comparison of the at least one
characteristic associated with the microbial component from an
anti-microbial region 202 proximate at least one of the outer
surface 106 or the inner surface 108 of the body structure 104 to
stored reference data, and to initiate a treatment protocol based
at least in part on the comparison, or deliver at least one
anti-microbial agent to at least one of the outer surface 106 or
the inner surface 108 of the body structure 104.
[0370] In an embodiment, the computing device 230 is configured to
perform a comparison of a real-time measurand associated with a
region proximate the insertable device 102 to infection marker or
biomarker information configured as a physical data structure 260
and to generate a response 299 based at least in part on the
comparison. In an embodiment, one or more computing devices 230 are
operably coupled to at least one of the selectively actuatable
anti-microbial regions 202a, and configured to actuate at least one
of the selectively actuatable anti-microbial regions 202a in
response 299 to detected information from the one or more sensors
302.
[0371] Referring to FIGS. 4A, 4B, 5A, and 5B, in an embodiment, the
plurality of selectively actuatable anti-microbial regions 202a are
configured to provide a spatial or temporal patterned 109
anti-microbial surface property 204. In an embodiment, the
plurality of selectively actuatable anti-microbial regions 202a are
configured to deliver an anti-microbial agent of a dose sufficient
(e.g., of character and for a duration sufficient, of sufficient
strength or duration, etc.) to provide a spatial or temporal
patterned 109 anti-microbial surface of the body structure 104.
[0372] In an embodiment, the insertable device 102 comprises a body
structure 104 having an outer surface 106, and an inner surface 108
defining one or more fluid-flow passageways 110; wherein at least
one of the outer surface 106, or the inner surface 108 of the body
structure 104 includes at least one anti-microbial nanostructure
206a.
[0373] In an embodiment, the insertable device 102 comprises a body
structure 104 including at least one anti-microbial nanostructure
206a. In an embodiment, the insertable device 102 comprises a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; wherein at least
one of the outer surface 106, or the inner surface 108 of the body
structure 104 includes at least one actuatable anti-microbial
nanostructure 206a.
[0374] In an embodiment, the insertable device 102 comprises a body
structure 104 including at least one actuatable anti-microbial
nanostructure 206a.
[0375] As indicated in FIG. 7, in an embodiment, a catheter system
100 comprises a body structure 104 having an outer surface 106 and
an inner surface 108 defining one or more fluid-flow passageways
110; and a plurality of selectively actuatable anti-microbial
regions 202a configured to direct at least one anti-microbial agent
to one or more areas of at least one of the outer surface 106 of
the body structure 104, the inner surface 108 of the body structure
104, or embedded in the internal body structure; and circuitry 602
configured for determining the presence of at least one
microorganism proximate to one or more areas of the body structure
104. In an embodiment, the circuitry 602 configured for determining
the presence of at least one microorganism includes at least one
sensor 302 operably coupled to a microorganism biomarker array. In
an embodiment, the circuitry 602 configured for determining the
presence of at least one microorganism includes at least one of an
electrochemical transducer 602a, optical transducer 602b,
biochemical transducer 602c, ultrasonic transducer 602d,
piezoelectric transducer 602e, or thermal transducer 602f. In an
embodiment, the circuitry 602 configured for determining the
presence of at least one microorganism includes at least one
thermal detector 602g, photovoltaic detector 602h or
photomultiplier detector 602i.
[0376] In an embodiment, the transcutaneous energy transfer system
914 is electromagnetically, magnetically, acoustically, optically,
inductively, electrically, or capacitively coupleable to an in vivo
power supply. In an embodiment, the transcutaneous energy transfer
system 914 includes at least one electromagnetically coupleable
power supply 916, magnetically coupleable power supply 918,
acoustically coupleable power supply 920, optically coupleable
power supply 922, inductively coupleable power supply 924,
electrically coupleable power supply 926, or capacitively
coupleable power supply 928. In an embodiment, the energy
transcutaneous transfer system 914 is configured to wirelessly
receive power from a remote power supply 930. For example, in an
embodiment the power source 900 includes at least one
biological-subject powered generator 704. In an embodiment, the
power source 900 includes a thermoelectric generator 706. In an
embodiment, the power source 900 includes a piezoelectric generator
708. In an embodiment, the power source 900 includes a MEMS
generator 710. In an embodiment, the power source 900 includes a
biomechanical energy harvesting generator 712.
[0377] In an embodiment, the power source 900 is configured to
wirelessly receive power from a remote power supply 930. In an
embodiment, the catheter device 102 includes one or more power
receivers 932 configured to receive power from an in vivo or ex
vivo power source. In an embodiment, the power source 900 is
configured to wirelessly receive power via at least one of an
electrical conductor or an electromagnetic waveguide. In an
embodiment, the power source 900 includes one or more power
receivers 932 configured to receive power from an in vivo or ex
vivo power source. In an embodiment, the in vivo power source
includes at least one of a thermoelectric generator, a
piezoelectric generator, a microelectromechanical systems
generator, or a biomechanical-energy harvesting generator.
[0378] In an embodiment, the catheter device 102 includes one or
more generators configured to harvest mechanical energy from for
example, acoustic waves, mechanical vibration, blood flow, and the
like. For example, in an embodiment, the power source 900 includes
at least one of a biological-subject (e.g., human)-powered
generator 904, a thermoelectric generator 906, piezoelectric
generator 908, electromechanical generator 910 (e.g., a
microelectromechanical systems (MEMS) generator, or the like),
biomechanical-energy harvesting generator 912, and the like.
[0379] In an embodiment, the biological-subject-powered generator
904 is configured to harvest thermal energy generated by the
biological subject. In an embodiment, the
biological-subject-powered generator 904 is configured to harvest
energy generated by the biological subject using at least one of a
thermoelectric generator 906, piezoelectric generator 908,
electromechanical generator 910 (e.g., a microelectromechanical
systems (MEMS) generator, or the like), biomechanical-energy
harvesting generator 912, and the like. For example, in an
embodiment, the biological-subject-powered generator 904 includes
one or more thermoelectric generators 906 configured to convert
heat dissipated by the biological subject into electricity. In an
embodiment, the biological-subject-powered generator 904 is
configured to harvest energy generated by any physical motion or
movement (e.g., walking,) by biological subject. For example, in an
embodiment, the biological-subject-powered generator 904 is
configured to harvest energy generated by the movement of a joint
within the biological subject. In an embodiment, the
biological-subject-powered generator 904 is configured to harvest
energy generated by the movement of a fluid (e.g., biological
fluid) within the biological subject.
[0380] The system 100, can include, among other things, a
transcutaneous energy transfer system 914. In an embodiment, the
catheter device 102 includes a transcutaneous energy transfer
system 914. For example, in an embodiment, the catheter device 102
includes one or more power receivers 932 configured to receive
power from at least one of an in vivo or an ex vivo power source.
In an embodiment, the transcutaneous energy transfer system 914 is
electromagnetically, magnetically, acoustically, optically,
inductively, electrically, or capacitively coupled to at least one
of the anti-microbial regions 202 (e.g., selectively actuatable
anti-microbial regions 202a), computing device 230, or sensor
302.
[0381] In an embodiment, the transcutaneous energy transfer system
914 is configured to transfer power from at least one of an in vivo
or an ex vivo power source to the catheter device 102. In an
embodiment, the transcutaneous energy transfer system 914 is
configured to transfer power to the catheter device 102 and to
recharge a power source 900a within the catheter device 102.
[0382] In an embodiment, the circuitry 602 configured to determine
the microorganism presence includes at least one sensor 302. In an
embodiment, the circuitry 602 configured to determine the
microorganism presence includes at least one sensor 302 having a
component identification code and configured to implement
instructions addressed to the sensor 302 according to the component
identification code. In an embodiment, the circuitry 602 configured
to determine the microorganism presence includes at least one
sensor 302 operably coupled to a microorganism colonization
biomarker array.
[0383] In an embodiment, the circuitry 602 configured to determine
the microorganism presence includes biofilm marker information
configured as a physical data structure. In an embodiment, the
physical data structure includes a characteristic information
section having characteristic microbial colonization spectral
information representative of the presence of a microbial
colonization proximate the insertable device 102.
[0384] The system 100 can include, among other things, circuitry
604 configured to obtain information. In an embodiment, the
circuitry 604 configured to obtain information includes circuitry
604 configured to obtain information associated with a delivery of
the optical energy. In an embodiment, the circuitry 604 configured
to obtain information includes circuitry 604 configured to obtain
at least one of a command stream, a software stream, and a data
stream.
[0385] The system 100 can include, among other things, circuitry
606 configured to store information. In an embodiment, the
circuitry 606 configured to store information includes one or more
data structures.
[0386] The system 100 can include, among other things, circuitry
608 configured to provide information. In an embodiment, the
circuitry 608 configured to provide information includes circuitry
608 configured to provide having infection marker information. In
an embodiment, the circuitry 608 configured to provide information
includes circuitry 608 configured to provide status information. In
an embodiment, the circuitry 608 configured to provide information
includes circuitry 608 configured to provide information regarding
the detection of at least one of the emitted optical energy or the
remitted optical energy. In an embodiment, the circuitry 608
configured to provide information includes circuitry 608 configured
to detect at least one delivered anti-microbial agent, or other
anti-microbial protruding elements 206 actuated.
[0387] The system 100 can include, among other things, circuitry
610 configured to perform a comparison of the determined at least
one characteristic associated with the biological sample 808
proximate the insertable device 102 to stored reference data
following the delivery of the anti-microbial surface property 204.
The insertable device 102 can include, among other things,
circuitry 602 configured to generate a response 299 based at least
in part on the comparison. The circuitry 602 configured to perform
a comparison can include, among other things, one or computing
devices 230 configured to perform a comparison of the at least one
characteristic associated with the biological sample 808 proximate
the insertable device 102 stored reference data following delivery
of the anti-microbial agent, and to generate a response 299 based
at least in part on the comparison.
[0388] In an embodiment, the insertable device 102 includes one or
more anti-microbial regions 202a that form part of a surface along
a longitudinal direction 120 of a fluid-flow passageway 110. In an
embodiment, the insertable device 102 includes one or more
anti-microbial regions 202a that form part of a surface along a
lateral direction 122 of a fluid-flow passageway 110. In an
embodiment, the insertable device 102 includes one or more
anti-microbial regions 202a that form part of a surface along a
helical direction 124 of a fluid-flow passageway 110. In an
embodiment, the one or more anti-microbial regions 202a are
configured to laterally, 122 internally direct, longitudinally 120
internally direct, or helically 124 internally direct at least a
portion of at least one anti-microbial property 204 within an
interior of at least one of the fluid-flow passageways 110. In an
embodiment, the one or more anti-microbial regions 202a are
configured to direct at least a portion of at least one
anti-microbial property 204 in peristaltic movement along one or
more fluid-flow passageways 110. In an embodiment, at least one
anti-microbial nanostructure 206a extends substantially
longitudinally 120 along at least one of the fluid-flow passageways
110. In an embodiment, at least one of the anti-microbial
nanostructures 206a extends substantially laterally 122 within at
least one of the fluid-flow passageways 110. In an embodiment, at
least one of the anti-microbial nanostructures 206a extends
substantially helically 124 along at least one of the fluid-flow
passageways 110.
[0389] In an embodiment, at least one of the anti-microbial regions
202a extends substantially longitudinally 120 along at least one of
the fluid-flow passageways 110. In an embodiment, at least one of
the anti-microbial regions 202a extends substantially laterally 122
within at least one of the fluid-flow passageways 110. In an
embodiment, at least one of the anti-microbial regions 202a extends
substantially helically 124 within at least one of the fluid-flow
passageways 110. In an embodiment, at least one of the
anti-microbial regions 202a extends substantially laterally 122
along a first portion of the body structure 104 and a different one
of the one or more anti-microbial regions 202a extends
substantially laterally 122 along a second portion of the body
structure 104. In an embodiment, at least one of the anti-microbial
regions 202a extends substantially helically 124 along a first
portion of the body structure 104 and a different one of the
anti-microbial regions 202a extends substantially helically along a
second portion of the body structure 104. In an embodiment, at
least one of the anti-microbial regions 202a extends substantially
longitudinally 120 along a first portion of the body structure 104
and a different one of the anti-microbial regions 202a extends
substantially longitudinally 120 along a second portion of the body
structure 104.
[0390] In an embodiment, one or more anti-microbial regions 202a
are configured to direct at least one first anti-microbial property
204 or anti-microbial agent along a substantially lateral 122
direction in one or more anti-microbial regions 202 of at least one
of the fluid-flow passageways 110 and configured to direct at least
one second anti-microbial property 204 along a substantially
longitudinal 120 direction in one or more anti-microbial regions
202 of at least one of the fluid-flow passageways 110. In an
embodiment, one or more anti-microbial regions 202 are configured
to direct at least a portion of a first anti-microbial property 204
along a substantially lateral 122 direction in a first region of at
least one of the fluid-flow passageways 110 and configured to
direct at least a portion of a second anti-microbial property 204
along a substantially lateral 122 direction in a second region of
the one or more fluid-flow passageways 110, the second region
different from the first region. In an embodiment, the one or more
anti-microbial regions 202a are configured to direct at least a
portion of a first anti-microbial property 204 along a
substantially longitudinal 120 direction in a first region of at
least one of the fluid-flow passageways 110 and configured to
direct at least a portion of a second anti-microbial property 204
along a substantially longitudinal 120 direction in a second region
of the one or more fluid-flow passageways 110, the second region
different from the first region. In an embodiment, the one or more
anti-microbial regions 202a are configured to externally direct at
least a portion of an anti-microbial property 204. In an
embodiment, the one or more anti-microbial regions 202a are
configured to direct at least a portion of a first anti-microbial
property 204 along a substantially helical 124 direction in a first
region of at least one of the fluid-flow passageways 110 and
configured to direct at least a portion of a second anti-microbial
property 204 along a substantially helical 124 direction in a
second region of the one or more fluid-flow passageways 110, the
second region different from the first region.
[0391] In an embodiment, a plurality of anti-microbial regions 202,
are disposed along the one or more fluid-flow passageways 110. In
an embodiment, a plurality of anti-microbial regions 202 are
configured to form at least a portion of at least one of the inner
surface 108 or outer surface 106 of the body structure 104. In an
embodiment, at least one of the anti-microbial regions 202 on the
inner surface 108 of the body structure 104 is different than at
least one of the anti-microbial regions 202 on the outer surface
106 or embedded in the body structure 104. In an embodiment at
least one of the anti-microbial regions 202 on the outer surface
106 of the body structure 104 is different than at least one of the
anti-microbial regions 202 on the inner surface 108 or embedded in
the body structure 104. In an embodiment, at least one of the
anti-microbial regions 202 embedded in the body structure 104 is
different than at least one of the anti-microbial regions 202 on
the outer surface 106 or the inner surface 108 of the body
structure 104.
[0392] The system 100 includes, among other things, circuitry 601
configured for obtaining information. In an embodiment, the
circuitry 601 configured for obtaining information includes
circuitry 601 configured for obtaining information associated with
delivery of at least one anti-microbial agent. In an embodiment,
the circuitry 601 configured for obtaining information includes
circuitry 601 configured for obtaining at least one of a command
stream, software stream, or data stream.
[0393] The system 100 includes, among other things, circuitry 603
configured for providing information. In an embodiment, the
circuitry 603 configured for providing information includes
circuitry 603 configured for providing microbial marker
information. In an embodiment, the circuitry 603 configured for
providing information includes circuitry 603 configured for
providing status information. In an embodiment, the circuitry 603
configured for providing information includes circuitry 603
configured for providing information regarding the detection of at
least one microbial component proximate to at least one of the
outer surface 106 or the inner surface 108 of the body structure
104. In an embodiment, the circuitry 601 configured for obtaining
information further includes circuitry 603 configured for providing
information.
[0394] The transcutaneous energy transfer system 914 can include,
among other things, an inductive power supply. In an embodiment,
the inductive power supply includes a primary winding operable to
produce a varying magnetic field. The catheter device 102 can
include, among other things, a secondary winding electrically
coupled to one or more energy emitters 220 for providing a voltage
to biological sample proximate the catheter device 102 in response
299 to the varying magnetic field of the inductive power supply. In
an embodiment, the transcutaneous energy transfer system 914
includes a secondary coil configured to provide an output voltage
ranging from about 10 volts to about 25 volts. In an embodiment,
the transcutaneous energy transfer system 914 is configured to
manage a duty cycle associated with emitting an effective amount of
the sterilizing energy stimulus from one or more energy emitters
220. In an embodiment, the transcutaneous energy transfer system
914 is configured to transfer power to the catheter device 102 and
to recharge a power source 900 within the catheter device 102.
[0395] In an embodiment, the insertable device 102 is, for example,
wirelessly coupled to a computing device 230 that communicates with
the insertable device 102 via wireless communication. Non-limiting
examples of wireless communication include optical connections,
ultraviolet connections, infrared, BLUETOOTH.RTM., Internet
connections, radio, network connections, and the like.
[0396] The system 100 can include, among other things, one or more
memories 250 that, for example, store instructions or data, for
example, volatile memory (e.g., Random Access Memory (RAM) 252,
Dynamic Random Access Memory (DRAM), or the like), non-volatile
memory (e.g., Read-Only Memory (ROM) 254, Electrically Erasable
Programmable Read-Only Memory (EEPROM), Compact Disc Read-Only
Memory (CD-ROM), or the like), persistent memory, or the like.
Further non-limiting examples of one or more memories 250 include
Erasable Programmable Read-Only Memory (EPROM), flash memory, and
the like. Various components of the insertable device 102 (e.g.,
memories 250, processors 232, or the like) can be operably coupled
to each other via one or more instruction 775, data 776, or power
buses 256.
[0397] Referring to FIG. 6, the system 100 can include, among other
things, circuitry 602 configured to determine a microorganism
presence in one or more anti-microbial regions 202 in proximity to
the insertable device 102, for example, proximate at least one of
the outer surface 106 or the inner surface 108 of the body
structure 104. Circuitry 602 can include one or more components
operably coupled (e.g., communicatively coupled,
electromagnetically, magnetically, acoustically, optically,
inductively, electrically, capacitively coupleable, or the like) to
each other. In an embodiment, circuitry 602 includes one or more
remotely located components. In an embodiment, remotely located
components are operably coupled via wireless communication. In an
embodiment, remotely located components are operably coupled via
one or more receivers 444, transmitters 445, transceivers 446, and
the like.
[0398] In an embodiment, the system 100 includes control circuitry
602 operably coupled to the one or more anti-microbial regions 202.
In an embodiment, the system 100 includes control circuitry 602
operably coupled to the active agent assemblies 800 (e.g.,
anti-microbial regions 202). In an embodiment, the control
circuitry 602 is configured to control delivery of at least one
active agent (including an anti-microbial agent) from one or more
anti-microbial regions 202. In an embodiment, the control circuitry
602 is configured to control delivery of at least one active agent
(including an anti-microbial agent) from at least one active agent
reservoir (e.g., anti-microbial agent reservoir 208). In an
embodiment, the at least one anti-microbial agent reservoir 208
includes an electricity storage device 701. In an embodiment, the
at least one electricity storage device 701 is rechargeable and
electricity can be reloaded into the storage device 701. In an
embodiment, at least one computing device 230 is operably coupled
to one or more selectively actuatable anti-microbial region 202a
and configured to control at least one of a delivery regimen,
spatial distribution, or temporal distribution associated with the
delivery of the active agent. In an embodiment, the one or more
computing devices 230 are configured to actuate at least one
selectively actuatable anti-microbial regions 202a in response to a
scheduled program, an external command, a history of a previous
microbial presence, a signal, data point, or a history of a
previous actuation. In an embodiment, the one or more computing
devices 230 are configured to control delivery of at least one
anti-microbial agent from an anti-microbial reservoir 208 of the
anti-microbial region 202.
[0399] In an embodiment, the system 100 includes at least one
computing device 230 communicably coupled to one or more
anti-microbial regions 202, and optionally configured to control at
least one parameter associated with selectively actuating one or
more anti-microbial regions 202.
[0400] In an embodiment, the plurality of selectively actuatable
anti-microbial regions 202a are configured to provide a spatial or
temporal patterned 109 anti-microbial surface property 204 at least
a first region 406 and a second region 408 different from the first
region 406. For example, in an embodiment, the second region 408
includes at least one of a spectral power distribution (SPD.sub.n),
an irradiance (I.sub.n), or a peak power (P.sub.n) different from
the first region 406. In an embodiment, the second region 408
includes at least one of an illumination intensity, peak emission
wavelength, or pulse frequency different from the first region 406.
In an embodiment, the second region 408 includes at least one of an
intensity, phase, or polarization different from the first region
406. In an embodiment, the second region 408 includes at least one
of a frequency, repetition rate, or bandwidth different from the
first region 406. In an embodiment, the second region 408 includes
at least one of an energy-emitting pattern, ON-pulse duration, or
OFF-pulse duration different from the first region 406. In an
embodiment, the second region 408 includes at least one of an
emission intensity, emission phase, emission polarization, or
emission wavelength different from the first region 406. In an
embodiment, the second region has at least one different
anti-microbial property 204 (e.g., structure, agent, reservoir,
etc.) different from the first region 406. For example, in an
embodiment, the second region 408 includes at least one of an
anti-microbial protruding element 206 (e.g., nanostructure 206a, or
other element) different than the first region 406. In an
embodiment, the second region 408 includes at least one of an
anti-microbial agent that is different than the first region
406.
[0401] The system 100 can include, among other things, one or more
modules optionally operable for communication with one or more
input/output components 266 that are configured to relay user
output and/or input. In an embodiment, a module includes one or
more instances of electrical, electromechanical,
software-implemented, firmware-implemented, or other control
devices. For example, in an embodiment, the insertable device 102,
includes a controller 388 operably coupled to the sensor 302. In an
embodiment, the at least one controller 388 is configured to be
responsive to the detected presence of at least one microorganism
by the at least one sensor 302. Such devices include one or more
instances of memory 250, computing devices 230, ports, valves,
fuses, antifuses, antennas, power, or other supplies; logic modules
or other signaling modules; gauges or other such active or passive
detection components; program instructions, or piezoelectric
transducers, shape memory elements, micro-electro-mechanical system
(MEMS) elements, or other actuators. In an embodiment, the
controller 388 is configured to activate at least one independently
addressable and actively controllable anti-microbial nanostructure
202a in response 299 to detected information from at least one
sensor 302. In an embodiment, the controller 388 is configured to
activate at least one independently addressable and actively
controllable anti-microbial nanostructure 206a in response 299 to
at least one of a scheduled program, external command, history of a
previous presence of a microorganism, or history of a previous
activation. In an embodiment, the system 100 further comprises
circuitry 602 configured for determining the presence of at least
one microorganism proximate the body structure 104 subsequent to a
first round of activation of at least one independently addressable
and actively controllable anti-microbial nanostructure 206a. In an
embodiment, the system 100 further comprises circuitry 602
configured for altering the type of response 299 of an
independently addressable and actively controllable anti-microbial
nanostructure 202a based on the determination of the presence of at
least one microorganism proximate the body structure 104 subsequent
to a first round of activation. In an embodiment, the system 100
further comprises electrically activating means (e.g., switches
118, etc.) for concurrently or sequentially electrically activating
two or more of the at least one independently addressable and
actively controllable anti-microbial nanostructure 202a determined
to have at least one microorganism present thereon.
[0402] The computer-readable media drive 264 or memory slot can be
configured to accept signal-bearing medium 777 (e.g.,
computer-readable memory media, computer-readable recording media,
or the like). In an embodiment, a program for causing the system
100 to execute any of the disclosed methods can be stored on, for
example, a computer-readable recording medium (CRMM) 262, or other
signal-bearing medium 777. Non-limiting examples of signal-bearing
media 777 include a recordable type medium such as a magnetic tape,
floppy disk, a hard disk drive, a Compact Disc (CD), a Digital
Video Disk (DVD), Blu-Ray Disc, a digital tape, a computer memory,
or the like, as well as transmission type medium such as a digital
and/or an analog communication medium (e.g., a fiber optic cable, a
waveguide, a wired communications link, a wireless communication
link (e.g., transmitter 445, receiver 444, transmission logic,
reception logic, etc.), etc.). Further non-limiting examples of
signal-bearing media 777 include, but are not limited to, DVD-ROM,
DVD-RAM, DVD+RW, DVD-RW, DVD-R, DVD+R, CD-ROM, Super Audio CD,
CD-R, CD+R, CD+RW, CD-RW, Video Compact Discs, Super Video Discs,
flash memory, magnetic tape, magneto-optic disk, MINIDISC,
non-volatile memory card, EEPROM, optical disk, optical storage,
RAM, ROM, system memory, web server, and the like.
[0403] For example, in an embodiment, the system 100 includes a
signal-bearing medium 777 bearing: one or more instructions for
operating an insertable device 102, the insertable device 102
including a body structure 104 having an outer surface 106 and an
inner surface 108 defining one or more fluid-flow passageways 110;
and one or more anti-microbial regions 202 proximate at least one
of an outer surface 106, an inner surface 108, or embedded in the
internal body structure 104; the body structure 104 including at
least one anti-microbial agent reservoir 208 operably coupled to
the one or more anti-microbial regions 202; and one or more
instructions for operating the at least one anti-microbial agent
reservoir 208. In an embodiment, the system 100 further comprises
one or more instructions for operating one or more sensor receivers
444 or sensor transmitters 445. In an embodiment, the
signal-bearing medium 777 includes a computer-readable medium. In
an embodiment, the signal-bearing medium 777 includes a recordable
medium or a communications medium.
[0404] In an embodiment, the system 100 includes a signal-bearing
medium 777 bearing: a body structure 104 having an outer surface
106 and an inner surface 108 defining one or more fluid-flow
passageways 110; at least one independently addressable and
actively controllable anti-microbial nanostructure 206a; and one or
more instructions for controlling the at least one independently
addressable and actively controllable anti-microbial nanostructure
206a of the body structure 104.
[0405] In an embodiment, an insertable device system 100, comprises
a body structure 104 having an outer surface 106 and an inner
surface 108 defining one or more fluid-flow passageways 110; at
least one independently addressable and actively controllable
anti-microbial nanostructure 206a projecting from at least one of
the outer surface 106, or the inner surface 108 of the body
structure 104; and circuitry configured 602 for determining the
presence of at least one microorganism on at least, one of the
independently addressable and actively controllable anti-microbial
nanostructure 206a of the body structure 104.
[0406] In an embodiment, the system 100 includes at least one
receiver 444 configured to acquire information based at least in
part on a detected microbial component (e.g. microbial marker
information). In an embodiment, the at least one receiver 444 is
configured to acquire instructions. In an embodiment, the at least
one receiver 444 is configured to acquire information based at
least in part on whether a detected microbial component from one or
more regions proximate at least one of the outer surface 106 or the
inner surface 108 of the body structure 104 satisfies a target
condition. In an embodiment, the at least one receiver 444 is
configured to acquire information associated with delivery of at
least one anti-microbial agent. In an embodiment, the at least one
receiver 444 is configured to receive one or more signals (e.g.,
acoustic signal, electromagnetic signal, optical signal, infrared
signal, radio signal, radio frequency signal, microwave signal,
ultrasonic signal, or biochemical signal). In an embodiment, the at
least one receiver 444 is configured to receive one or more signals
according to one or more schedules. In an embodiment, the at least
one receiver 444 is configured to receive one or more signals in
response 299 to detection of at least one microbial component. In
an embodiment, the at least one receiver 444 is configured to
receive one or more signals in response 299 to one or more queries.
In an embodiment, the at least one receiver 444 is configured to
acquire data, or acquire software. In an embodiment, the at least
one receiver 444 is configured to receive stored reference data. In
an embodiment, the at least one receiver 444 is configured to
receive data from one or more distal sensors 302. In an embodiment,
the at least one receiver 444 is configured to receive stored
reference data.
[0407] In an embodiment, the system 100 includes at least one
transmitter 445 configured to send information based at least in
part on historical action taken with regard to at least one
anti-microbial region 202. In an embodiment, the historical action
taken includes at least one of activation or response 299 to at
least one microorganism. In an embodiment, the at least one
transmitter 445 is configured to send a request for transmission of
at least one of data, command, authorization, update, or code. In
an embodiment, the system 100 includes circuitry 601 configured for
obtaining information; and circuitry 603 configured for providing
information. In an embodiment, the at least one transmitter 445 is
configured to transmit one or more signals (e.g., acoustic signal,
electromagnetic signal, optical signal, infrared signal, radio
signal, radio frequency signal, microwave signal, ultrasonic
signal, or biochemical signal). In an embodiment, the at least one
transmitter 445 is configured to transmit one or more signals
according to one or more schedules. In an embodiment, the at least
one transmitter 445 is configured to transmit one or more signals
in response 299 to detection of at least one microbial component.
In an embodiment, the at least one transmitter 445 is configured to
transmit in response 299 to the status of at least one of the level
of anti-microbial agent in the reservoir 208, or release of the at
least one anti-microbial agent from the reservoir 208. In an
embodiment, the at least one transmitter 445 is configured to
transmit one or more signals in response 299 to one or more
queries. In an embodiment, the at least one transmitter 445 is
configured to transmit one or more encrypted signals.
[0408] In an embodiment, the system 100 comprises: a signal-bearing
medium 777 bearing: a body structure 104 having an outer surface
106 and an inner surface 108 defining one or more fluid-flow
passageways 110; at least one independently addressable and
actively controllable anti-microbial nanostructure 206a; and one or
more instructions for determining the presence of at least one
microorganism on at least one of the independently addressable and
actively controllable anti-microbial nanostructure 206a of the body
structure 104.
[0409] In an embodiment, the system 100 includes signal-bearing
media 777 in the form of one or more logic devices (e.g.,
programmable logic devices, complex programmable logic device,
field-programmable gate arrays, application specific integrated
circuits, or the like) comprising, for example, a data structure
260 including one or more look-up tables. The system 100 can
include, among other things, signal-bearing media 777 having sample
information (e.g., biological sample 808 information, reference
information, characteristic spectral information, or the like)
configured as a data structure 260. In an embodiment, the data
structure 260 includes at least one of psychosis state indication
information, psychosis trait indication information, or
predisposition for a psychosis indication information. In an
embodiment, the data structure 260 includes at least one of
infection indication information, inflammation indication
information, diseased state indication information, or diseased
tissue indication information.
[0410] Many of the disclosed embodiments can be electrical,
electromechanical, software-implemented, firmware-implemented, or
other otherwise implemented, or combinations thereof. Many of the
disclosed embodiments can be software or otherwise in memory, such
as one or more executable instruction sequences or supplemental
information as described herein. For example, in an embodiment, the
insertable device 102 can include, among other things, one or more
computing devices 230 configured to perform a comparison of the at
least one characteristic associated with the biological subject 222
to stored reference data, and to generate a response 299 based at
least in part on the comparison.
[0411] As indicated in FIG. 8, in an embodiment, the system 100
includes a cryptographic logic component 221. In an embodiment, the
cryptographic logic component 221 is configured to implement at
least one cryptographic process or cryptographic logic. In an
embodiment, the cryptographic logic component 221 is configured to
implement one or more processes associated with at least one of a
cryptographic protocol, decryption protocol, or encryption
protocol. In an embodiment, the cryptographic logic component 221
is configured to implement one or more processes associated with at
least one of a regulatory compliance protocol, regulatory use
protocol, or authentication protocol. In an embodiment, the
cryptographic logic component 221 is configured to implement one or
more processes associated with at least one of an authorization
protocol, activation protocol, or treatment regimen protocol. In an
embodiment, the cryptographic logic component 221 is configured to
generate information associated with at least one of an
authentication protocol, authorization protocol, delivery of at
least one anti-microbial agent protocol, activation protocol,
encryption protocol, or decryption protocol. In an embodiment, the
cryptographic logic component 221 is configured to generate
information associated with at least one of an authorization
instruction, authentication instruction, prescription dosing
instruction, anti-microbial agent administration instruction, or
prescribed regimen instruction. In an embodiment the cryptographic
logic component 221 is configured to generate information
associated with at least one of an instruction stream, encrypted
data stream, authentication data stream, or authorization data
stream. In an embodiment, the cryptographic logic component 221 is
configured to generate information associated with at least one of
an activation code, error code, command code, or authorization
code. In an embodiment, the cryptographic logic component 221 is
configured to generate information associated with at least one of
a cryptographic protocol, decryption protocol, encryption protocol,
regulatory compliance protocol, or regulatory use protocol.
[0412] In an embodiment, the insertable device 102 includes at
least one outer internally reflective coating 708 on a body
structure 104 defining the one or more fluid-flow passageways 110.
In an embodiment, the insertable device 102 includes at least one
inner internally reflective coating 709 on a body structure 104
defining the one or more fluid-flow passageways 110.
[0413] In an embodiment, the system 100 is configured to initiate
one or more medical protocols 399 (e.g. clinical trial protocol,
diagnostic protocol, treatment protocol, etc.). In an embodiment,
the system 100 is configured to initiate at least one medical
protocol 399 based on a detected spectral event. In an embodiment,
the system 100 is configured to initiate at least one medical
protocol 399 based on a detected biomarker event. In an embodiment,
the system 100 is configured to initiate at least one medical
protocol 399 based on a detected infection. In an embodiment, the
system 100 is configured to initiate at least one medical protocol
399 based on a detected a fluid vessel abnormalities (e.g., an
obstruction), a detected biological sample 808 abnormality (e.g.,
cerebrospinal fluid abnormalities, hematological abnormalities,
components concentration or level abnormalities, flow
abnormalities, or the like), a detected biological parameter, or
the like.
[0414] In an embodiment, the system 100 can include, among other
things, one or more active agent assemblies 800 (including but not
limited to, anti-microbial reservoirs 208). In an embodiment, the
insertable device 102 includes at least one active agent assembly
800 including one or more anti-microbial reservoir 208. In an
embodiment, the at least one anti-microbial reservoir 208 is
actuatable by the presence of at least one microorganism. In an
embodiment, the anti-microbial reservoir 208 is configured for at
least one of active or passive delivery of the at least one
anti-microbial agent. In an embodiment, the at least one
anti-microbial reservoir 208 is configured for time-release of at
least one anti-microbial agent.
[0415] In an embodiment, an insertable device 102 includes a body
structure 104 having an outer surface 106 and an inner surface 108
defining one or more fluid-flow passageways 110; one or more
anti-microbial regions 202 of the body structure 104 including at
least one selectively actuatable anti-microbial agent reservoir 208
configured to be actuatable by the presence of at least one
microorganism, and configured to actively deliver one or more
anti-microbial agents to the one or more anti-microbial regions 202
of the body structure 104.
[0416] In an embodiment, the active agent assembly 800 is
configured to deliver one or more active agents from the at least
one active agent reservoir (e.g., anti-microbial agent reservoir
208) to one or more anti-microbial regions proximate the body
structure 104. For example, in an embodiment, the insertable device
102 includes one or more active agent assemblies 800 configured to
deliver at least one active agent from the at least one
anti-microbial reservoir 208 to at least one of a region proximate
an outer surface 108 and a region proximate an inner surface 110 of
the insertable device 102.
[0417] In an embodiment, the anti-microbial reservoir 208 includes
at least one active agent composition. Non-limiting examples of
active agents include adjuvants, allergens, analgesics,
anesthetics, antibacterial agents, antibiotics, antifungals,
anti-inflammatory agents (e.g., nonsteroidal anti-inflammatory
drugs), antimicrobials, anti-parasitic, antioxidants, antipyretics,
anti-tumor agents, antivirals, bio-control agents, biologics or
bio-therapeutics, chemotherapy agents, disinfecting agents,
energy-actuatable active agents, anti-clotting factor, vaccine,
small molecule, nutraceutical, vitamin, mineral, anti-microbial
agent, immunogens, immunological adjuvants, immunological agents,
immuno-modulators, immuno-response agents, immuno-stimulators
(e.g., specific immuno-stimulators, non-specific
immuno-stimulators, or the like), immuno-suppressants,
non-pharmaceuticals (e.g., cosmetic substances, or the like),
pharmaceuticals, protease inhibitors or enzyme inhibitors, receptor
agonists, receptor antagonists, therapeutic agents, tolerogens,
toll-like receptor agonists, toll-like receptor antagonists,
vaccines, or combinations thereof.
[0418] Further non-limiting examples of active agents include
nonsteroidal anti-inflammatory drugs such as acemetacin, aclofenac,
aloxiprin, amtolmetin, aproxen, aspirin, azapropazone, benorilate,
benoxaprofen, benzydamine hydrochloride, benzydamine hydrochloride,
bromfenal, bufexamac, butibufen, carprofen, celecoxib, choline
salicylate, clonixin, desoxysulindac, diflunisal, dipyone,
droxicam, etodolac, etofenamate, etoricoxib, felbinac, fenbufen,
fenoprofen, fentiazac, fepradinol, floctafenine, flufenamic acid,
indomethacin, indoprofen, isoxicam, ketoralac, licofelone,
lomoxicam, loxoprofen, magnesium salicylate, meclofenamic acid,
meclofenamic acid, mefenamic acid, meloxicam, morniflumate,
niflumic acid, nimesulide, oxaprozen, phenylbutazone, piketoprofen,
piroxicam, pirprofen, priazolac, propyphenazone, proquazone,
rofecoxib, salalate, salicylamide, salicylic acid, sodium
salicylate, sodium thiosalicylate, sulindac, suprofen, tenidap,
tenoxicam, tiaprofenic acid, tolmetin, tramadol, trolamine
salicylate, zomepirac, or the like.
[0419] Further non-limiting examples of active agents include
energy-actuatable active agents (e.g., chemical energy, electrical
resistance, laser energy, terahertz energy, microwave energy,
optical energy, radio frequency energy, acoustic energy, thermal
energy, thermal resistance heating energy, or ultrasonic energy
actuatable active agents, or the like) and the like.
[0420] In an embodiment, the active agent includes at least one
active agent that selectively targets bacteria. For example, in an
embodiment, the active agent includes at least one bacteriophage
that can, for example, selectively target bacteria. Bacteriophages
generally comprise an outer protein hull enclosing genetic
material. The genetic material can be ssRNA, dsRNA, ssDNA, or
dsDNA. Bacteriophages are generally smaller than the bacteria they
destroy generally ranging from about 20 nm to about 200 nm.
Non-limiting examples of bacteriophages include T2, T4, T6,
phiX-174, MS2, or the like). In an embodiment, the active agent
includes at least one energy-actuatable agent that selectively
targets bacteria. For example, in an embodiment, the active agent
includes at least one triplet excited-state photosensitizer that
can, for example, selectively target bacteria.
[0421] Further non-limiting examples of active agents include
triplet excited-state photosensitizers, reactive oxygen species,
reactive nitrogen species, any other inorganic or organic ion or
molecules that include oxygen ions, free radicals, peroxides, or
the like. Further non-limiting examples of active agents include
compounds, molecules, or treatments that elicit a biological
response from any biological subject 222. Further non-limiting
examples of disinfecting agents include therapeutic agents (e.g.,
antimicrobial therapeutic agents), pharmaceuticals (e.g., a drug, a
therapeutic compound, pharmaceutical salts, or the like)
non-pharmaceuticals (e.g., a cosmetic substance, or the like),
neutraceuticals, antioxidants, phytochemicals, homeopathic agents,
and the like. Further non-limiting examples of disinfecting agents
include peroxidases (e.g., haloperoxidases such as
chloroperoxidase, or the like), oxidoreductase (e.g.,
myeloperoxidase, eosinophil peroxidase, lactoperoxidase, or the
like) oxidases, and the like.
[0422] Further non-limiting examples of active agents include one
or more pore-forming toxins. Non limiting examples of pore-forming
toxins include beta-pore-forming toxins, e.g., hemolysin,
Panton-Valentine leukocidin S, aerolysin, Clostridial
epsilon-toxin; binary toxins, e.g., anthrax, C. perfringens lota
toxin, C. difficile cytolethal toxins; cholesterol-dependent
cytolysins; pneumolysin; small pore-forming toxins; and gramicidin
A.
[0423] Further non-limiting examples of active agents include one
or more pore-forming antimicrobial peptides. Antimicrobial peptides
represent an abundant and diverse group of molecules that are
naturally produced by many tissues and cell types in a variety of
invertebrate; plant and animal species. The amino acid composition,
amphipathicity, cationic charge and size of antimicrobial peptides
allow them to attach to and insert into microbial membrane bilayers
to form pores leading to cellular disruption and death. More than
800 different antimicrobial peptides have been identified or
predicted from nucleic acid sequences, a subset of which are
available in a public database (see, e.g., Wang & Wang, Nucleic
Acids Res. 32:D590-D592, 2004); http://aps.unmc.edu/AP/main.php,
the contents of each of which is incorporated herein by
reference).
[0424] More specific examples of antimicrobial peptides include,
among others, anionic peptides, e.g., maximin H5 from amphibians,
small anionic peptides rich in glutamic and aspartic acids from
sheep, cattle and humans, and dermcidin from humans; linear
cationic alpha-helical peptides, e.g., cecropins (A), andropin,
moricin, ceratotoxin, and melittin from insects, cecropin P1 from
Ascaris nematodes, magainin 2, dermaseptin, bombinin, brevinin-1,
esculentins and buforin II from amphibians, pleurocidin from skin
mucous secretions of the winter flounder, seminalplasmin, BMAP,
SMAP (SMAP29, ovispirin), PMAP from cattle, sheep and pigs, CAP18
from rabbits and LL37 from humans; cationic peptides enriched for
specific amino acids, e.g., praline-containing peptides including
abaecin from honeybees, praline- and arginine-containing peptides
including apidaecins from honeybees, drosocin from Drosophila,
pyrrhocoricin from European sap-sucking bug, bactenicins from
cattle (Bac7), sheep and goats and PR-39 from pigs, praline- and
phenylalanine-containing peptides including prophenin from pigs,
glycine-containing peptides including hymenoptaecin from honeybees,
glycine- and praline-containing peptides including coleoptericin
and holotricin from beetles, tryptophan-containing peptides
including indolicidin from cattle, and small histidine-rich
salivary polypeptides, including histatins from humans and higher
primates; anionic and cationic peptides that contain cysteine and
from disulfide bonds, e.g., peptides with one disulphide bond
including brevinins, peptides with two disulfide bonds including
alpha-defensins from humans (HNP-1, HNP-2, cryptidins), rabbits
(NP-1) and rats, beta-defensins from humans (HBD1, DEFB118),
cattle, mice, rats, pigs, goats and poultry, and rhesus
theta-defensin (RTD-1) from rhesus monkey, insect defensins
(defensin A); and anionic and cationic peptide fragments of larger
proteins, e.g., lactoferricin from lactoferrin, casocidin 1 from
human casein, and antimicrobial domains from bovine
alpha-lactalbumin, human hemoglobin, lysozyme, and ovalbumin (see,
e.g., Brogden, Nat. Rev. Microbiol. 3:238-250, 2005, which is
incorporated herein by reference).
[0425] Further non-limiting examples of active agents include
antibacterial drugs. Non-limiting examples of antibacterial drugs
include beta-lactam compounds such as penicillin, methicillin,
nafcillin, oxacillin, cloxacillin, dicloxacillin, ampicillin,
ticarcillin, amoxicillin, carbenicillin, and piperacillin;
cephalosporins and cephamycins such as cefadroxil, cefazolin,
cephalexin, cephalothin, cephapirin, cephradine, cefaclor,
cefamandole, cefonicid, cefuroxime, cefprozil, loracarbef,
ceforanide, cefoxitin, cefmetazole, cefotetan, cefoperazone,
cefotaxime, ceftazidine, ceftizoxine, ceftriaxone, cefixime,
cefpodoxime, proxetil, cefdinir, cefditoren, pivoxil, ceftibuten,
moxalactam, and cefepime; other beta-lactam drugs such as
aztreonam, clavulanic acid, sulbactam, tazobactam, ertapenem,
imipenem, and meropenem; other cell wall membrane active agents
such as vancomycin, teicoplanin, daptomycin, fosfomycin,
bacitracin, and cycloserine; tetracyclines such as tetracycline,
chlortetracycline, oxytetracycline, demeclocycline, methacycline,
doxycycline, minocycline, and tigecycline; macrolides such as
erythromycin, clarithromycin, azithromycin, and telithromycin;
aminoglycosides such as streptomycin, neomycin, kanamycin,
amikacin, gentamicin, tobramycin, sisomicin, and netilmicin;
sulfonamides such as sulfacytine, sulfisoxazole, silfamethizole,
sulfadiazine, sulfamethoxazole, sulfapyridine, and sulfadoxine;
fluoroquinolones such as ciprofloxacin, gatifloxacin, gemifloxacin,
levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, and
ofloxacin; antimycobacteria drugs such as isoniazid, rifampin,
rifabutin, rifapentine, pyrazinamide, ethambutol, ethionamide,
capreomycin, clofazimine, and dapsone; and miscellaneous
antimicrobials such as colistimethate sodium, methenamine
hippurate, methenamine mandelate, metronidazole, mupirocin,
nitrofurantoin, polymyxin B, clindamycin, choramphenicol,
quinupristin-dalfopristin, linezolid, spectrinomycin, trimethoprim,
pyrimethamine, and trimethoprim-sulfamethoxazole.
[0426] Further non-limiting examples of active agents include
antifungal agents. Non-limiting examples of antifungal agents
include anidulafungin, amphotericin B, butaconazole, butenafine,
caspofungin, clotrimazole, econazole, fluconazole, flucytosine
griseofulvin, itraconazole, ketoconazole, miconazole, micafungin,
naftifine, natamycin, nystatin, oxiconazole, sulconazole,
terbinafine, terconazole, tioconazole, tolnaftate, and/or
voriconazole.
[0427] Further non-limiting examples of active agents include
anti-parasite agents. Non-limiting examples of anti-parasite agents
include antimalaria drugs such as chloroquine, amodiaquine,
quinine, quinidine, mefloquine, primaquine,
sulfadoxine-pyrimethamine, atovaquone-proguanil,
chlorproguanil-dapsone, proguanil, doxycycline, halofantrine,
lumefantrine, and artemisinins; treatments for amebiasis such as
metronidazole, iodoquinol, paromomycin, diloxanide furoate,
pentamidine, sodium stibogluconate, emetine, and dehydroemetine;
and other anti-parasite agents such as pentamidine, nitazoxanide,
suramin, melarsoprol, eflornithine, nifurtimox, clindamycin,
albendazole, and timidazole. Further non-limiting examples of
active agents include ionic silver, (SilvaSorb.RTM., Medline
Industries, Inc), anti-microbial silver compositions (Arglaes.RTM.,
Medline Industries, Inc), or the like. Further non-limiting
examples of active agents include superoxide-forming compositions.
Further non-limiting examples of active agents include
oxazolidinones, gram-positive antibacterial agents, or the like.
See, e.g., U.S. Pat. No. 7,322,965 (issued Jan. 29, 2008), which is
incorporated herein by reference.
[0428] In an embodiment, the active agent includes one or more
antimicrobial agents. In an embodiment, the antimicrobial agent is
an antimicrobial peptide. Amino acid sequence information for a
subset of these can be found as part of a public database (see,
e.g., Wang & Wang, Nucleic Acids Res. 32:D590-D592, 2004);
http://aps.unmc.edu/AP/main.php, which is incorporated herein by
reference). Alternatively, a phage library of random peptides can
be used to screen for peptides with antimicrobial properties
against live bacteria, fungi and/or parasites. The DNA sequence
corresponding to an antimicrobial peptide can be generated ex vivo
using standard recombinant DNA and protein purification
techniques.
[0429] In an embodiment, one or more of the active agent include
chemicals suitable to disrupt or destroy cell membranes. For
example, some oxidizing chemicals can withdraw electrons from a
cell membrane causing it to, for example, become destabilized.
Destroying the integrity of cell membranes of, for example, a
pathogen can lead to cell death.
[0430] In an embodiment, the insertable device 102 includes one or
more active agent assemblies 800 configured to deliver at least one
active agent from the at least one reservoir 208 to at least one of
a region proximate an outer surface 106 or an inner surface 108 of
the insertable device 102. In an embodiment, at least one of the
active agent assemblies 800 is configured to deliver one or more
active agents in a spatially or temporally patterned distribution.
In an embodiment, at least one of the active agent assemblies 800
is configured to deliver one or more active agents in a temporally
patterned distribution. In an embodiment, the insertable device 102
includes a plurality of spaced-apart-release-ports 118a adapted to
deliver one or more active agents in a spatially patterned
distribution. In an embodiment, the insertable device 102 includes
a plurality of spaced apart controllable-release ports 118a adapted
to deliver one or more active agents in a spatially patterned
distribution.
[0431] In an embodiment, the insertable device 102 includes a
release system 799.
[0432] In an embodiment, the insertable device 102 includes at
least one computing device 230 operably coupled to one or more of
the plurality of spaced-apart-release-ports 118a and configured to
actuate one or more of the plurality of spaced-apart-release-ports
between an active agent discharge state and an active agent
retention state. In an embodiment, a computing device 230 is
operable to actuate one or more of the plurality of
spaced-apart-release-ports 118a between an active agent discharge
state and an active agent retention state based on a comparison of
a detected characteristic to stored reference data.
[0433] In an embodiment, the computing device 230 is operably
coupled to the active agent assembly and configured to actively
control one or more of the plurality of spaced-apart-release-ports
118a. In an embodiment, at least one computing device 230 is
operably coupled to one or more of the spaced-apart
controllable-release ports 118a and configured to control at least
one of a port release rate, a port release amount, and a port
release pattern associated with a delivery of the one or more
active agents. In an embodiment, at least one processor 232 is
operably coupled to the active agent assembly 800 (e.g., an
anti-microbial reservoir 208) and configured to control at least
one of a port release rate, a port release amount, and a port
release pattern associated with the delivery of the one or more
active agents from the at least one active agent reservoir 208 to
an interior of the one or more fluid-flow passageways 110.
[0434] In an embodiment, a computing device 230 is operably coupled
to the active agent assembly 800 and configured to control at least
one of an active agent delivery rate, an active agent delivery
amount, an active agent delivery composition, a port release rate,
a port release amount, and a port release pattern.
[0435] In an embodiment, at least one computing device 230 is
operably coupled to one or more of the plurality of
spaced-apart-release-ports 118a and configured to actuate one or
more of the plurality of spaced-apart-release-ports 118a between an
active agent discharge state and an active agent retention state.
In an embodiment, the insertable device 102 includes one or more
active agent assemblies 800 including one or more active agent
reservoir 208 configured to deliver at least one active agent from
the at least one active agent (e.g., anti-microbial agent)
reservoir 208 to at least one of a region proximate an outer
surface 108 and a region proximate an inner surface 110 of the
insertable device 102.
[0436] In an embodiment, the insertable device 102 includes one or
more active agent assemblies 800 configured to deliver one or more
disinfecting agents. In an embodiment, the insertable device 102
includes one or more active agent assemblies 800 configured to
deliver at least one energy-actuatable agent from at least one
reservoir 208 to, for example, an interior of one or more
fluid-flow passageways 110. Non-limiting examples of
energy-actuatable active agents include radiation absorbers, light
energy absorbers, X-ray absorbers, photoactive agents, and the
like. Non-limiting examples of photoactive agents include, but are
not limited to photoactive antimicrobial agents (e.g., eudistomin,
photoactive porphyrins, photoactive TiO.sub.2, antibiotics, silver
ions, antibodies, nitric oxide, or the like), photoactive
antibacterial agents, photoactive antifungal agents, and the like.
Further non-limiting examples of energy-actuatable agent includes
energy-actuatable disinfecting agents, photoactive agents, or a
metabolic precursor thereof. In an embodiment, the at least one
energy-actuatable agent includes at least one X-ray absorber. In an
embodiment, the at least one energy-actuatable agent includes at
least one radiation absorber.
[0437] In an embodiment, the active agent assembly 800 is
configured to deliver at least one energy-actuatable disinfecting
agent from at least one reservoir 208 to a biological sample 808
proximate the insertable device 102. In an embodiment, the
insertable device 102 includes one or more active agent assemblies
800 configured to deliver at least one energy-actuatable
disinfecting agent from the at least one active agent reservoir 208
to a biological sample 808 proximate at least one surface of the
insertable device 102. In an embodiment, at least one of the active
agent assemblies 800 is configured to deliver at least one
energy-actuatable disinfecting agent in a spatially patterned
distribution. In an embodiment, the active agent assembly 800 is
configured to deliver at least one energy-actuatable steroid to
biological sample 808 proximate the at least one outer surface 108
of the insertable device 102.
[0438] The at least one active agent reservoir 208 can include,
among other things, an acceptable carrier. In an embodiment, at
least one active agent is carried by, encapsulated in, or forms
part of, an energy-sensitive (e.g., energy-actuatable), carrier,
vehicle, vesicle, pharmaceutical vehicle, pharmaceutical carrier,
pharmaceutically acceptable vehicle, pharmaceutically acceptable
carrier, or the like.
[0439] Non-limiting examples of carriers include any matrix that
allows for transport of a disinfecting agent across any tissue,
cell membranes, and the like of a biological subject 222, or that
is suitable for use in contacting a biological subject 222, or that
allows for controlled release formulations of the compositions
disclosed herein. Further non-limiting examples of carriers include
at least one of creams, liquids, lotions, emulsions, diluents,
fluid ointment bases, gels, organic and inorganic solvents,
degradable or non-degradable polymers, pastes, salves, vesicle, and
the like. Further non-limiting examples of carriers include cyclic
oligosaccharides, ethasomes, hydrogels, liposomes, micelle,
microspheres, nisomes, non-ionic surfactant vesicles, organogels,
phospholipid surfactant vesicles, phospholipid surfactant vesicles,
transfersomes, virosomes. Further non-limiting examples of
energy-sensitive carriers and the like include electrical
energy-sensitive, light sensitive, pH-sensitive, ion-sensitive,
acoustic energy sensitive, ultrasonic energy sensitive
carriers.
[0440] In an embodiment, one or more active agents are carried by
energy-sensitive vesicles (e.g., energy-sensitive cyclic
oligosaccharides, ethasomes, hydrogels, liposomes, micelles,
microspheres, nisomes, non-ionic surfactant vesicles, organogels,
phospholipid surfactant vesicles, transfersomes, virosomes, and the
like.). In an embodiment, at least one of the energy emitters 220
is configured to provide energy of a dose sufficient to liberate at
least a portion of an active agent carried by the energy-sensitive
vesicles.
[0441] In an embodiment, the insertable device 102 includes one or
more biological sample compartment 708. In an embodiment, the
insertable device 102 includes one or more active agent assemblies
800 configured to receive one or more biological samples 808. In an
embodiment, the biological sample compartment 708 is placed under
the scalp of a user. In an embodiment, the biological sample
compartment 708 is configured to allow for the removal of
biological sample with a syringe. In an embodiment, the biological
sample compartment 708 includes a sensor 302 configured to detect,
for example, bacteria, cancer cells, blood, or proteins of a fluid
sample received within. In an embodiment, the sensor 302 is
operably coupled to the at least one biological sample compartment
708 (e.g., operably coupled to at least one selectively actuatable
anti-microbial agent reservoir 208). In an embodiment, the
biological sample compartment 708 is configured to allow the
injection or introduction of antibiotics for cerebrospinal fluid
infection or chemotherapy medication. In an embodiment, the
biological sample compartment 708 includes circuitry configured to
detect at least one physical quantity, environmental attribute, or
physiologic characteristic associated with, for example, a shunting
process. In an embodiment, the sensor 302 is configured to detect
at least one microorganism proximate at least one anti-microbial
nanostructure 206a. In an embodiment, the sensor 302 is configured
to detect at least one microorganism proximate at least one
anti-microbial region 202a. In an embodiment, the at least one
sensor 302 is operably associated with at least one anti-microbial
nanostructure 206a within at least one of the fluid-flow
passageways 110. In an embodiment, the at least one sensor 302 is
configured to detect at least one microorganism in one or more
fluid-flow passageways 110 based at least in part on one or more
flow characteristics.
[0442] In an embodiment, a plurality of the selectively actuatable
anti-microbial regions 202a form at least one spatial or temporal
pattern extending over at least a portion of the body structure
104. In an embodiment, the selectively actuatable anti-microbial
region 202a (optionally including an anti-microbial reservoir 208)
are capable of at least one of independent or dependent
actuation.
[0443] In an embodiment, the insertable device 102 includes one or
more active agent assemblies 800 configured to deliver at least one
tracer agent from at least one reservoir 208. In an embodiment, the
insertable device 102 includes one or more active agent assemblies
800 including one or more tracer agent reservoir 208 configured to
deliver at least one tracer agent. In an embodiment, the one or
more active agent assemblies 800 are configured to deliver one or
more tracer agents. Non-limiting examples of tracer agents include
one or more in vivo clearance agents, magnetic resonance imaging
agents, contrast agents, dye-peptide compositions, fluorescent
dyes, or tissue specific imaging agents. In an embodiment, the one
or more tracer agents include at least one fluorescent dye. In an
embodiment, the one or more tracer agents include indocyanine
green.
[0444] In an embodiment, active agent assembly 800 is further
configured to concurrently or sequentially deliver one or more
tracer agents and one or more energy-actuatable disinfecting
agents. In an embodiment, the active agent assembly 800 is further
configured to deliver one or more tracer agents for indicating the
presence or concentration of one or more energy-actuatable
disinfecting agents in at least a region proximate the insertable
device 102. In an embodiment, the active agent assembly 800 is
further configured to deliver one or more tracer agents for
indicating the response of the one or more energy-actuatable
disinfecting agents to energy emitted from the one or more
energy-emitting emitters 302.
[0445] In an embodiment, one or more fluid-flow passageways 110
include a photoactive agent. In an embodiment, one or more
fluid-flow passageways 110 include a photoactive coating material.
In an embodiment, one or more fluid-flow passageways 110 include a
photoactive agent configured to emit ultraviolet light energy in
the presence of an energy stimulus. In an embodiment, the one or
more fluid-flow passageways 110 include a photoactive agent
configured to emit ultraviolet light energy in the presence of an
electrical potential. In an embodiment, the one or more fluid-flow
passageways 110 include a photoactive agent having one or more
photoabsorption bands in the visible region of the electromagnetic
spectrum.
[0446] Various methods for reducing, inhibiting, or eliminating
growth or adherence of at least one microorganism are disclosed
herein, each of which can utilize additional steps disclosed, for
example in FIGS. 9-28, or throughout the specification. For
example, as depicted in FIG. 9, a method 1500 includes activating
1501 at least one anti-microbial region of a plurality of
anti-microbial regions of at least one of an outer surface, an
inner surface, or embedded in a body structure of an insertable
device, the body structure defining one or more fluid-flow
passageways, based on an automatically detected biomarker
associated with at least one microorganism. In an embodiment, 1510
wherein activating the at least one anti-microbial region includes
activating a spatially or temporally patterned anti-microbial
region in at least one of the plurality of anti-microbial regions
of the body surface. In an embodiment 1520 wherein activating the
at least one anti-microbial region is based at least in part on one
or more of a detected fluorescence, detected impedance, detected
optical reflectance, detected thermal transfer, or detected
microbial component. In an embodiment 1530 wherein activating the
at least one anti-microbial region is initiated at least one of
prior to, during, or subsequent to insertion of the insertable
device into a biological subject. In an embodiment 1540 wherein
activating the at least one anti-microbial region is based at least
in part on one or more of current biomarker information, previous
biomarker information, or previous activation events. In an
embodiment 1550 the method is implemented by at least one computing
device. In an embodiment 1555 the method further comprises
generating at least one output to a user. In an embodiment 1560
wherein the at least one output includes at least one of a
treatment protocol, identification of a detected microorganism,
status of the insertable device, or location of a detected
microorganism. In an embodiment 1570 wherein the at least one
output occurs in real-time. In an embodiment 1580 wherein the at
least one output is associated with historical information. In an
embodiment 1590 the user includes at least one entity. In an
embodiment 1591 the at least one entity includes at least one
person or computer. In an embodiment 1592, the at least one output
includes output to a user readable display. In an embodiment 1593
the user readable display includes a human readable display. In an
embodiment 1594 the user readable display includes at least one of
a passive display or active display. In an embodiment 1599 the user
readable display is coupled to the insertable device.
[0447] As depicted in FIG. 10, a method 1600 includes 1610
actuating at least one anti-microbial region of a plurality of
anti-microbial regions configured to direct at least one
anti-microbial agent to one or more areas of at least one of an
outer surface, an inner surface, or internally embedded in a body
structure of an insertable device, the body structure defining one
or more fluid-flow passageways, in response to an in vivo detected
microbial component associated with a biological sample proximate
to one or more areas of the body structure.
[0448] As depicted in FIG. 11, a method 1700 includes 1705
automatically comparing one or more characteristics communicated
from an inserted insertable device to stored reference data, the
one or more characteristics including at least one of information
associated with microbial marker information; and information
associated with at least one microbial component detected proximate
to at least one of an outer surface or inner surface of the
insertable device, or information associated with a fluid received
within one or more fluid-flow passageways of the inserted
insertable device; and initiating a treatment protocol based at
least in part on the comparison. In an embodiment 1710
automatically comparing the one or more characteristics
communicated from an inserted insertable device to stored reference
data includes comparing, via circuitry forming part of the inserted
insertable device, one or more characteristic is communicated from
the inserted insertable device to stored reference data. In an
embodiment 1720 initiating the treatment protocol includes
generating a spatially patterned distribution of at least one
anti-microbial agent released from at least one anti-microbial
region of the device. In an embodiment 1730 initiating the
treatment protocol includes delivering a dose of at least one
anti-microbial agent based at least in part on the comparison. In
an embodiment 1740 initiating the treatment protocol includes
concurrently or sequentially delivering two or more anti-microbial
agents to at least one of the outer surface, or the inner surface
of the body structure of the insertable device, based at least in
part on the comparison. In an embodiment 1750 initiating the
treatment protocol includes activating at least one of an
authorization protocol, authentication protocol, or anti-microbial
agent delivery protocol based at least in part on the
comparison.
[0449] As depicted in FIG. 12, a method 1800 includes activating at
least one activatable anti-microbial region including at least one
anti-microbial reservoir configured to actively elute at least one
anti-microbial agent proximate at least one of the outer surface or
the inner surface of the body structure of the device, based at
least in part on detecting the presence of at least one
microorganism proximate to one or more areas of the body
structure.
[0450] As depicted in FIG. 13, a method 1900 includes 1905
selectively releasing at least one antimicrobial agent from an
anti-microbial agent reservoir operably coupled to one or more
anti-microbial regions proximate at least one of an outer surface,
inner surface, or embedded in the internal body structure of an
insertable device, the insertable device including a body structure
having an outer surface and an inner surface defining one or more
fluid-flow passageways, in response to an automatically detected
signal associated with the at least one microbial component
proximate at least one of the outer surface or inner surface of the
insertable device, or present in the fluid-flow passageway. In an
embodiment 1910, selectively releasing at least one anti-microbial
agent from an anti-microbial agent reservoir operably coupled to
one or more anti-microbial regions includes concurrently or
sequentially releasing at least one first anti-microbial agent from
an anti-microbial agent reservoir operably coupled to a first
anti-microbial region, and releasing at least one second
anti-microbial agent from an anti-microbial agent reservoir
operably coupled to a second anti-microbial agent reservoir.
[0451] In an embodiment 1920, releasing the at least one
anti-microbial agent includes releasing the anti-microbial agent at
a dose sufficient to modulate an activity of the detected
microorganism in response to the automatically detected signal
associated with at least one microbial component. In an embodiment
1930, the method further comprises initiating a treatment protocol
in response to the automatically detected signal associated with at
least one microbial component proximate at least one of the outer
surface or inner surface of the insertable device. In an embodiment
1940 initiating the treatment protocol includes activating at least
one of an authorization protocol, authentication protocol, or
anti-microbial agent delivery protocol, based at least in part on
the automatically detected signal associated with at least one
microbial component.
[0452] As depicted in FIG. 14, a method 2000, includes 2005 a
method implemented by at least one computing device. In an
embodiment 2010, the method further comprises generating at least
one output to a user. In an embodiment 2020, the at least one
output includes at least one output to a user readable display. In
an embodiment 2030 the at least one output includes at least one of
a treatment protocol, identification of a detected microorganism,
status of the insertable device, or location of a detected
microorganism. In an embodiment 2040 the user includes at least one
entity. In an embodiment 2050 the at least one entity includes at
least one person or computer. In an embodiment 2060 the at least
one output includes at least one output to a user readable display.
In an embodiment 2070 the user readable display includes a human
readable display. In an embodiment 2080 the user readable display
includes one or more active displays. In an embodiment 2090, the
user readable display includes one or more passive displays. In an
embodiment 2094 the at least one output occurs in real-time. In an
embodiment 2095 the user readable display includes one or more of a
numeric format, graphical format, or audio format. In an embodiment
2096 the signal includes at least one of a fluorescent signal,
impedance signal, optical signal, thermal signal, biochemical
signal, or electrochemical signal. In an embodiment 2097,
selectively releasing the at least one anti-microbial agent is
initiated at least one of prior to, during, or subsequent to
insertion of the insertable device into a biological subject. In an
embodiment 2098 the at least one output is associated with
historical information. In an embodiment 2099 the user readable
display is coupled to the insertable device.
[0453] As depicted in FIG. 15, a method 2100 includes 2110
selectively actuating one or more anti-microbial regions so as to
partially release at least one anti-microbial agent through at
least one of an outer surface or an inner surface of the catheter
assembly in response to real-time detected information associated
with the presence of a microbial component proximate one or more
regions of at least one of an outer surface or inner surface of the
catheter assembly.
[0454] As depicted in FIG. 16, a method 2200 includes 2210
activating via control circuitry at least one actively controllable
anti-microbial nanostructure of at least one of the outer surface
or the inner surface in a body structure of an insertable device.
In an embodiment 2215 the body structure defines one or more
fluid-flow passageways, based on at least one of an automatically
detected biomarker, temporal randomness, or a heuristically
determined parameter associated with at least one microorganism. In
an embodiment 2220 wherein activating the at least one actively
controllable anti-microbial nanostructure includes electrically
activating a spatially patterned anti-microbial nanostructure. In
an embodiment 2230 activating the at least one actively
controllable anti-microbial nanostructure includes electrically
activating a temporally patterned anti-microbial nanostructure. In
an embodiment 2240 the actuation is based at least in part on
detection of at least one microorganism. In an embodiment 2250 the
actuation is based at least in part on a schedule. In an embodiment
2260 the actuation is based at least in part on a command from an
implant. In an embodiment 2270 the actuation is based at least in
part on a command from one or more sensors. In an embodiment 2280
the actuation is based at least in part on an external command.
[0455] As depicted in FIG. 17, a method 2300 includes 2305
activating the at least one actively controllable anti-microbial
nanostructure includes activating a spatially patterned
anti-microbial nanostructure based on at least one characteristic.
In an embodiment 2310, the at least one characteristic includes at
least one detected characteristic including one or more of a
detected fluorescence, detected impedance, detected optical
reflectance, detected thermal transfer, detected change in
conductance, detected change in index of refraction, detected pH,
or detected microbial component of at least one microorganism. In
an embodiment 2320 activating the at least one actively
controllable anti-microbial nanostructure is initiated at least one
of prior to, during, or subsequent to insertion of the insertable
device into a biological subject. In an embodiment 2330, the method
includes electrically activating a computing device to execute the
method. In an embodiment 2340 the method further comprises
generating at least one output to a user. In an embodiment 2350
generating at least one output to the user includes electrically
activating at least one of a treatment protocol, identification of
a detected microorganism, status of the insertable device, or
location of a detected microorganism. In an embodiment 2360
generating at least one output to the user includes generating at
least one output to at least one entity. In an embodiment 2365 the
at least one entity includes at least one person or computer. In an
embodiment 2370 the at least one output includes at least one
output to a user readable display. In an embodiment 2380 the user
readable display includes one or more active displays. In an
embodiment 2390 the user readable display includes one or more
passive displays. In an embodiment 2395 the user readable display
includes one or more of a numeric format, graphical format, or
audio format.
[0456] As depicted in FIG. 18, a method 2400 includes 2405 the
heuristically determined parameter includes at least one of a
threshold level or target parameter. In an embodiment 2410 the
heuristically determined parameter includes at least one heuristic
protocol determined parameter or heuristic algorithm determined
parameter.
[0457] As depicted in FIG. 19, a method 2500 includes 2505
activating via control circuitry at least one independently
addressable and actively controllable anti-microbial nanostructure
projecting from at least one of the outer surface or the inner
surface of a body structure of an insertable device, the body
structure defining one or more fluid-flow passageways, based on at
least one of an automatically detected biomarker or a heuristically
determined parameter associated with at least one microorganism. In
an embodiment 2506 activating the at least one actively
controllable anti-microbial nanostructure includes activating a
spatially patterned anti-microbial nanostructure. In an embodiment
2507 activating the at least one actively controllable
anti-microbial nanostructure includes activating a temporally
patterned anti-microbial nanostructure.
[0458] As depicted in FIG. 20, a method 2600 includes 2605
actuating at least one anti-microbial region between a first
anti-microbial state and a second anti-microbial state, the at
least one anti-microbial region included in at least one of the
outer surface or the inner surface of a body structure of an
insertable device, the body structure defining one or more
fluid-flow passageways, based at least in part on an automatically
detected biomarker or a heuristically determined parameter
associated with at least one microorganism. In an embodiment 2610,
actuating includes reversibly actuating between the first
actuatable anti-microbial state and the second actuatable
anti-microbial state in response to a detected presence of at least
one microbial component. In an embodiment 2620, the first
actuatable anti-microbial state includes a first adsorption
affinity, and the second actuatable anti-microbial state includes a
second adsorption affinity. In an embodiment 2630, actuating
between the at least one of the first actuatable anti-microbial
state or the second actuatable anti-microbial state includes at
least one of a change in at least one of hydrophilicity,
hydrophobicity, electrical charge, chemical composition,
polarizability, transparence, conductivity, light absorption,
osmotic potential, zeta potential, surface energy, coefficient of
friction, or tackiness. In an embodiment 2640, actuating the at
least one actively controllable anti-microbial nanostructure
includes actuating a spatially patterned anti-microbial
nanostructure based on at least one of detected fluorescence,
detected impedance, detected optical reflectance, detected thermal
transfer, detected change in conductance, detected change in index
of refraction, detected pH, or detected microbial component. In an
embodiment 2650, the actuation is based at least in part on a
schedule, command from an implant, command from one or more
sensors, or external command. In an embodiment 2660, the method
further comprises generating at least one output to a user.
[0459] As depicted in FIG. 21, a method 2700 includes 2705
actuating at least one independently addressable and actuatable
anti-microbial region, the at least one independently addressable
and actuatable anti-microbial region included in at least one of
the outer surface or the inner surface of a body structure of an
insertable device, the body structure defining one or more
fluid-flow passageways, based at least in part on an automatically
detected biomarker or a heuristically determined parameter
associated with at least one microorganism.
[0460] As depicted in FIG. 22, a method 2800 includes 2805
actuating one or more anti-microbial regions of an insertable
device between at least a first actuatable anti-microbial state and
a second actuatable anti-microbial state in response to a detected
presence of at least one microbial component proximate at least one
of the one or more anti-microbial regions of an insertable device.
In an embodiment 2810, actuating includes reversibly actuating
between the first actuatable anti-microbial state and the second
actuatable anti-microbial state in response to a detected presence
of at least one microbial component. In an embodiment 2820 the
first actuatable anti-microbial state includes a first adsorption
affinity, and the second actuatable anti-microbial state includes a
second adsorption affinity. In an embodiment 2830, actuating
between the at least one of the first actuatable anti-microbial
state or the second actuatable anti-microbial state includes at
least one of a change in at least one of hydrophilicity,
hydrophobicity, electrical charge, chemical composition,
polarizability, transparence, conductivity, light absorption,
osmotic potential, zeta potential, surface energy, coefficient of
friction, or tackiness.
[0461] As depicted in FIG. 23, a method 2900 includes actuating at
least one anti-microbial region of a plurality of anti-microbial
regions configured to direct at least one anti-microbial agent to
one or more areas of at least one of an outer surface, an inner
surface, or internally embedded in a body structure of an
insertable device, the body structure defining one or more
fluid-flow passageways, in response to an in vivo detected
microbial component associated with a biological sample proximate
to one or more areas of the body structure. In an embodiment 2905,
actuating the at least one anti-microbial region including
actuating at least one spatially patterned or temporally patterned
anti-microbial region in at least one of the plurality of
anti-microbial regions of the body surface. In an embodiment 2906,
actuating the at least one anti-microbial region is based at least
in part on at least one of a detected fluorescence, detected
impedance, detected optical reflectance, detected thermal transfer,
or detected microbial component. In an embodiment 2907, actuating
the at least one anti-microbial region is initiated at least one of
prior to, during, or subsequent to insertion of the insertable
device into a biological subject. In an embodiment 2908 actuating
the at least one anti-microbial region is based at least in part on
one or more of current biomarker information, previous biomarker
information, or previous actuation events.
[0462] As depicted in FIG. 24, a method 3000 includes 3010
activating the at least one actively controllable anti-microbial
nanostructure is based at least in part on detection of at least
one microorganism. In an embodiment 3020, activating the at least
one actively controllable anti-microbial nanostructure is based at
least in part on a schedule. In an embodiment 3030, activating the
at least one actively controllable anti-microbial nanostructure is
based at least on part on a command from an implant. In an
embodiment 3040, activating the at least one actively controllable
anti-microbial nanostructure is based at least in part on a command
from one or more sensors. In an embodiment 3050, activating the at
least one actively controllable anti-microbial nanostructure is
based at least in part on an external command. In an embodiment
3060, activating the at least one actively controllable
anti-microbial nanostructure includes activating a spatially
patterned anti-microbial nanostructure based on a detected
fluorescence. In an embodiment 3070, activating the at least one
actively controllable anti-microbial nanostructure includes
activating a spatially patterned anti-microbial nanostructure based
on a detected impedance. In an embodiment 3080 activating the at
least one actively controllable anti-microbial nanostructure
includes activating a spatially patterned anti-microbial
nanostructure based on a detected optical reflectance.
[0463] As depicted in FIG. 25, a method 3100 includes 3110
activating the at least one actively controllable anti-microbial
nanostructure includes activating a spatially patterned
anti-microbial nanostructure based on a detected thermal transfer.
In an embodiment 3120 activating the at least one actively
controllable anti-microbial nanostructure includes activating a
spatially patterned anti-microbial nanostructure based on a
detected change in conductance. In an embodiment 3130, activating
the at least one actively controllable anti-microbial nanostructure
includes activating a spatially patterned anti-microbial
nanostructure based on a detected change in index of refraction. In
an embodiment 3140, activating the at least one actively
controllable anti-microbial nanostructure includes activating a
spatially patterned anti-microbial nanostructure based on a
detected pH. In an embodiment 3150, activating the at least one
actively controllable anti-microbial nanostructure includes
activating a spatially patterned anti-microbial nanostructure based
on a detected microbial component of at least one microorganism. In
an embodiment 3160, activating the at least one actively
controllable anti-microbial nanostructure includes electrically
activating a computing device to execute the method. In an
embodiment 3170, activating the at least one actively controllable
anti-microbial nanostructure is initiated at least one of prior to,
during, or subsequent to insertion of the insertable device into a
biological subject.
[0464] As depicted in FIG. 26, a method 3200 includes 3210
actuating the one or more anti-microbial regions based at least in
part on detection of at least one microorganism. In an embodiment
3220 actuating the one or more anti-microbial regions is based at
least in part on a schedule. In an embodiment 3230 actuating the
one or more anti-microbial regions is based at least in part on a
command from an implant. In an embodiment 3240 actuating the one or
more anti-microbial regions is based at least in part on a command
from one or more sensors. In an embodiment 3250, actuating the one
or more anti-microbial regions is based at least in part on an
external command. In an embodiment 3260, actuating the one or more
anti-microbial regions includes actuating a spatially patterned
anti-microbial region based on a detected fluorescence. In an
embodiment 3270, actuating the one or more anti-microbial regions
includes activating a spatially patterned anti-microbial region
based on a detected impedance. In an embodiment 3280 actuating the
one or more anti-microbial regions includes actuating a spatially
patterned anti-microbial region based on a detected optical
reflectance.
[0465] As depicted in FIG. 27, a method 3300 includes 3310
actuating the one or more anti-microbial regions includes actuating
a spatially patterned anti-microbial region based on a detected
thermal transfer. In an embodiment 3320 actuating the one or more
anti-microbial regions includes actuating a spatially patterned
anti-microbial region based on a detected change in conductance. In
an embodiment 3330 actuating the one or more anti-microbial regions
includes actuating a spatially patterned anti-microbial region
based on a detected change in index of refraction. In an embodiment
3340 actuating the one or more anti-microbial regions includes
actuating a spatially patterned anti-microbial region based on a
detected pH. In an embodiment 3350 actuating the one or more
anti-microbial regions includes actuating a spatially patterned
anti-microbial region based on a detected microbial component of at
least one microorganism. In an embodiment 3360 actuating the one or
more anti-microbial regions includes electrically activating a
computing device to execute the method. In an embodiment 3370
actuating the one or more anti-microbial regions is initiated at
least one of prior to, during, or subsequent to insertion of the
insertable device into a biological subject.
[0466] As depicted in FIG. 28, a method 3400 includes 3401
actuating at least one actuatable anti-microbial region including
at least one anti-microbial reservoir configured to actively elute
at least one anti-microbial agent proximate at least one of the
outer surface or the inner surface of the body structure of the
device, based at least in part on detecting the presence of at
least one microorganism proximate to one or more areas of the body
structure.
[0467] As depicted in FIG. 29, a method 3500 includes 3510 at least
one anti-microbial region including one or more of an
anti-microbial agent, or anti-microbial nanostructure. In an
embodiment 3520 the anti-microbial agent includes at least one
surfactant or amino acid. In an embodiment 3530 the amino acid
includes at least one D-amino acid. In an embodiment 3540 the
anti-microbial agent includes at least one of an anti-fungal agent,
anti-parasitic agent, bacteriophage, or antibiotic. In an
embodiment 3550 the anti-microbial agent includes at least one
enzymatically active bacteriophage. In an embodiment 3560, the
antibiotic includes at least one of azithromycin, clarithromycin,
clindamycin, dirithromycin, erythromycin, lincomycin,
troleandomycin, cinoxacin, ciprofloxacin, enoxacin, gatifloxacin,
grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic
acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, oxolinic
acid, gemifloxacin, perfloxacin, imipenem-cilastatin, meropenem,
aztreonam, amikacin, gentamicin, kanamycin, neomycin, netilmicin,
streptomycin, tobramycin, paromomycin, teicoplanin, vancomycin,
demeclocycline, doxycycline, methacycline, minocycline,
oxytetracycline, tetracycline, chlortetracycline, mafenide,
sulfadizine, sulfacetamide, sulfadiazine, sulfamethoxazole,
sulfasalazine, sulfisoxazole, trimethoprim-sulfamethoxazole,
sulfamethizole, linezolid, quinopristin+dalfopristin, bacitracin,
chloramphenicol, colistemetate, fosfomycin, isoniazid, methenamine,
metronidazol, mupirocin, nitrofurantoin, nitrofurazone, novobiocin,
polymyxin B, spectinomycin, trimethoprim, coliistin, cycloserine,
capreomycin, ethionamide, pyrazinamide, para-aminosalicyclic acid,
erythromycin ethylsuccinate+sulfisoxazole, penicillin,
beta-lactamase inhibitor, methicillin, cefaclor, cefamandole
nafate, cefazolin, cefixime, cefinetazole, cefonioid, cefoperazone,
ceforanide, cefotanme, cefotaxime, cefotetan, cefoxitin,
cefpodoxime proxetil, ceftazidime, ceftizoxime, ceftriaxone,
cefriaxone moxalactam, cefuroxime, cephalexin, cephalosporin C,
cephalosporin C sodium salt, cephalothin, cephalothin sodium salt,
cephapirin, cephradine, cefuroximeaxetil, dihydratecephalothin,
moxalactam, loracarbef mafate, Amphotericin B, Carbol-Fuchsin,
Ciclopirox, Clotrimzole, Econazole, Haloprogin, Ketoconazole,
Mafenide, Miconazole, Naftifine, Nystatin, Oxiconazole Silver,
Sulfadiazine, Sulconazole, Terbinatine, Tioconazole, Tolnaftate,
Undecylenic acid, flucytosine, miconazole or cephalosporin.
[0468] As depicted in FIG. 30, a method 3600 includes 3610 an
anti-microbial agent including at least one of a macrolide,
lincosamine, quinolone, fluoroquinolone, carbepenem, monobactam,
aminoglycoside, glycopeptide, enzyme, tetracycline, sulfonamide,
rifampin, oxazolidonone, streptogramin, or a synthetic moiety
thereof. In an embodiment 3620, the anti-microbial agent includes
at least one of a metal, ceramic, super-oxide forming compound, or
polymer. In an embodiment 3630, the anti-microbial agent includes
at least one of polyvinyl chloride, polyester, polyethylene,
polypropylene, ethylene, polyolefin, homopolymers or copolymers
thereof. In an embodiment 3640, the anti-microbial agent includes
polytetrafluoroethylene. In an embodiment 3650, at least one of the
plurality of anti-microbial regions includes at least one of
silver, copper, zirconium, diamond, rubidium, platinum, gold,
nickel, lead, cobalt, potassium, zinc, bismuth, tin, cadmium,
chromium, aluminum, calcium, mercury, thallium, gallium, strontium,
barium, lithium, magnesium, oxides, hydroxides, or salts thereof.
In an embodiment 3660, the at least one of the plurality of
anti-microbial regions includes at least one of an electroactive
polymer, hydrogenated diamond, or black silica.
[0469] 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 examples, and that in fact, many other
architectures can be implemented that achieve the same
functionality. 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 coupleable," to each other to achieve the
desired functionality. Specific examples of operably coupleable
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.
[0470] In an embodiment, one or more components may be referred to
herein as "configured to," "configurable to," "operable/operative
to," "adapted/adaptable," "able to," "conformable/conformed to,"
etc. Such terms (e.g., "configured to") can generally encompass
active-state components and/or inactive-state components and/or
standby-state components, unless context requires otherwise.
[0471] 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 the reader 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. Further, the use of "Start," "End" or "Stop"
blocks in the block diagrams is not intended to indicate a
limitation on the beginning or end of any functions in the diagram.
Such flowcharts or diagrams may be incorporated into other
flowcharts or diagrams where additional functions are performed
before or after the functions shown in the diagrams of this
application. In an embodiment, several portions of the subject
matter described herein is implemented via Application Specific
Integrated Circuits (ASICs), Field Programmable Gate Arrays
(FPGAs), digital signal processors (DSPs), or other integrated
formats. However, 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,
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. Non-limiting
examples of a signal-bearing Medium include the following: a
recordable type medium such as a floppy disk, a hard disk drive, a
Compact Disc (CD), a Digital Video Disk (DVD), a digital tape, a
computer memory, etc.; and a transmission type medium such as a
digital and/or an analog communication medium (e.g., a fiber optic
cable, a waveguide, a wired communications link, a wireless
communication link (e.g., transmitter, receiver, transmission
logic, reception logic, etc.), etc.).
[0472] While particular aspects of the present subject matter
described herein have been shown and described, it will be apparent
to the reader that, based upon the teachings herein, changes and
modifications can be made without departing from the subject matter
described herein and its broader aspects and, therefore, the
appended claims are to encompass within their scope all such
changes and modifications as are within the true spirit and scope
of the subject matter described herein. 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 among other
things," the term "having" should be interpreted as "having at
least," the term "includes" should be interpreted as "includes but
is not limited to," etc.). Further, if a specific number of an
introduced claim recitation is intended, such an intent will be
explicitly recited in the claim, and in the absence of such
recitation no such intent is present. For example, as an aid to
understanding, the following appended claims may contain usage of
the introductory phrases "at least one" and "one or more" to
introduce claim recitations. However, the use of such phrases
should not be construed to imply that the introduction of a claim
recitation by the indefinite articles "a" or "an" limits any
particular claim containing such introduced claim recitation to
claims containing only one such recitation, even when the same
claim includes the introductory phrases "one or more" or "at least
one" and indefinite articles such as "a" or "an" (e.g., "a" and/or
"an" should typically be interpreted to mean "at least one" or "one
or more"); the same holds true for the use of definite articles
used to introduce claim recitations. In addition, even if a
specific number of an introduced claim recitation is explicitly
recited, 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 of 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 of 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.). Typically a
disjunctive word and/or phrase presenting two or more alternative
terms, whether in the description, claims, or drawings, should be
understood to contemplate the possibilities of including one of the
terms, either of the terms, or both terms unless context dictates
otherwise. For example, the phrase "A or B" will be typically
understood to include the possibilities of "A" or "B" or "A and
B."
[0473] With respect to the appended claims, the operations recited
therein generally may be performed in any order. Also, although
various operational flows are presented in a sequence(s), it should
be understood that the various operations may be performed in
orders other than those that are illustrated, or may be performed
concurrently. Examples of such alternate orderings includes
overlapping, interleaved, interrupted, reordered, incremental,
preparatory, supplemental, simultaneous, reverse, or other variant
orderings, unless context dictates otherwise. Furthermore, terms
like "responsive to," "related to," or other past-tense adjectives
are generally not intended to exclude such variants, unless context
dictates otherwise.
[0474] While various aspects and embodiments have been disclosed
herein, other aspects and embodiments are contemplated. 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