Biologically integrated electrode devices

• US 20070060815A1
• Filed: 08/30/2006
• Published: 03/15/2007
• Est. Priority Date: 08/31/2005
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Martin, David, Richardson-Burns, Sarah, Kim, Donghwan, Povlich, Laura, Meier, Matthew, Abidian, Mohamad, Hendricks, Jeffrey
• Granted Patent: US 8,005,526 B2
• Time in Patent Office: Days
• US Class Current: 600/372
• CPC Class Codes: A61B 2562/0217 Electrolyte containing
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/25 Bioelectric electrodes therefor
• CPC Class Codes: A61B 5/266 containing electrolytes, conductive gels or pastes
• CPC Class Codes: A61B 5/268 containing conductive polymers, e.g. PEDOT:PSS polymers
• CPC Class Codes: A61N 1/05 for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence

Abstract

Bioelectrodes having enhanced biocompatible and biomimetic features are provided. Methods of making and using the bioelectrodes are further provided. A biologically integrated bioelectrode device and method for detecting electronic signals using a bioelectrode comprising a first electrically conductive substrate and a biological component. The bioelectrode also comprises a conductive polymer electrically coupling the first electrically conductive substrate and the biological component to define a bioelectrode. The bioelectrode can transmit or receive an electrical signal between the electrically conductive substrate and the biological component and conductive polymer.

Claims

1. A biologically integrated bioelectrode device comprising:

(i) a first electrically conductive substrate;

(ii) a biological component; and

(iii) a conductive polymer electrically coupling said first electrically conductive substrate to said biological component to collectively define a bioelectrode, said bioelectrode transmitting or receiving an electrical signal between the first electrically conductive substrate any one of said biological component and conductive polymer.

2. The biologically integrated bioelectrode device according to claim 1, wherein said biological component includes one or more of a tissue, organic living cell, a cellular constituent or combinations thereof.

3. The biologically integrated bioelectrode device according to claim 2, wherein said organic living cell is selected from the group consisting essentially of natural or recombinant eukaryotic cells and prokaryotic cells.

4. The biologically integrated bioelectrode device according to claim 2, said cellular constituent is selected from the group consisting essentially of a membrane, an organelle, an ion-channel, a lipid bi-layer, a receptor, an enzyme, a protein, an antibody, an antigen, a nucleic acid or combinations thereof.

5. The biologically integrated bioelectrode device according to claim 3, wherein said eukaryotic cells is selected from the group consisting essentially of cardiac cells, neural cells, muscle cells, stem cells, stromal cells, hematopoietic cells and combinations thereof.

6. The biologically integrated bioelectrode device according to claim 5, wherein said neural cells comprise neurons.

7. The biologically integrated bioelectrode device according to claim 1, wherein said bioelectrode further comprises at least one hydrogel in proximate contact with said conductive polymer.

8. The biologically integrated bioelectrode device according to claim 7, wherein said hydrogel further comprises a bioactive substance.

9. The biologically integrated bioelectrode device according to claim 1, wherein said conductive polymer is chosen from the group consisting essentially of copolymers and homopolymers of EDOT, pyrrole, and their functionalized derivatives and copolymers, polyanilines, salt of polyaniline, polyacetylenes, polythiophenes, a poly(3,4-ethylenedithiathiophene), polymer blends thereof, hybrid polymer-metal materials and combinations thereof.

10. The biologically integrated bioelectrode device according to claim 9, wherein the polymers of EDOT and pyrrole is chosen from the group consisting essentially of poly(3,4-ethylenedioxythiophene) (PEDOT), poly(pyrrole), their derivatives and combinations thereof.

11. The biologically integrated bioelectrode device according to claim 1, wherein said conductive polymer is polymerized around said biological component and said first electrically conductive substrate.

12. The biologically integrated bioelectrode device according to claim 1, wherein said first electrically conductive substrate contains a conductor chosen from the group consisting essentially of gold, silver, platinum, palladium, tungsten, nickel, titanium, indium tin oxide, copper, carbon, carbon black, carbon fiber, carbon paste, graphite, doped silicon, ceramic, conductive polymer, and combinations thereof.

13. The biologically integrated bioelectrode device according to claim 1, wherein said bioelectrode further comprises one or more dopants participating in polymerization of the conducting polymer and transmitting or receiving said electrical signal between the first electrically conductive substrate and said conductive polymer.

14. The biologically integrated bioelectrode device according to claim 1, further comprising a second electrically conductive substrate.

15. The biologically integrated bioelectrode device according to claim 1, further comprising an electrical source of power or current operable to communicate with said first and second electrode substrates and the biological component using one or more electrical signals with the device.

16. A biologically compatible electrode comprising:

(a) an electrically conductive substrate;

(b) a coating on at least some portion of at least one surface of said electrically conductive substrate, the coating comprising;

(i) a biological component, and

(ii) a conductive polymer,

wherein at least some of said conductive polymer is disposed and polymerized in proximate contact with said biological component and the electrically conductive substrate.

17. A biocompatible and biomimetic coating for an electrically conductive substrate comprising:

(a) an electrically conductive polymer, and

(b) a biological component,

wherein at least some of said electrically conductive polymer is disposed and polymerized in proximate contact with said biological component and the electrically conductive substrate.

18. The biocompatible and biomimetic coating according to claim 17, wherein said coating is applied to microelectrode arrays, lab on chip devices and target analyte detection devices.

19. A method of electrically detecting a transfer of electrical signals between living cells, comprising the steps:

(a) providing a bioelectrode device comprising a first electrically conductive substrate in intimate contact with tissue capable of transferring electronic charge, said bioelectrode device comprising;

(i) a first electrically conductive substrate;

(ii) a biological component; and

(iii) a conductive polymer electrically coupling said first electrically conductive substrate to said biological component to collectively define a bioelectrode, said bioelectrode transmitting or receiving an electrical signal between said first electrically conductive substrate any one of said biological component and conductive polymer,

(b) electrically connecting said bioelectrode device and a second electrically conductive substrate electrically coupled with said bioelectrode to a power source; and

(c) applying a voltage or current across said first and second electrically conductive substrates, thereby inducing a voltage or current across said conductive polymer;

(d) detecting the transfer of electrical signals with said bioelectrode device.

20. The method according to claim 19, wherein step (a)(ii) providing a bioelectrode device comprising a biological component, said biological component is chosen from the group consisting essentially of cardiac cells, neural cells and muscle cells.

21. The method according to claim 19, wherein the detecting step (c) comprises detecting the transfer of electrical signals wherein said signal is selected from the group consisting essentially of impedance, resistance, capacitance, inductance, and current.

22. The method according to claim 19, wherein said conductive polymer is chosen from the group consisting essentially of copolymers and homopolymers of EDOT, pyrrole, and their functionalized derivatives and copolymers, polyanilines, salt of polyaniline, polyacetylenes, polythiophenes, a poly(3,4-ethylenedithiathiophene), polymer blends thereof, hybrid polymer-metal materials and combinations thereof.

23. The method according to claim 22, wherein the copolymers and homopolymers of EDOT and pyrrole is chosen from the group consisting essentially of poly(3,4-ethylenedioxythiophene) (PEDOT), poly(pyrrole), and combinations thereof.

24. A method of detecting a biological material in a liquid or gas comprising the steps of:

(a) disposing a first and second electrically conductive substrate on a support;

(b) applying a conducting gel comprising a biological component, a hydrogel and a conductive monomer to form a layer on a portion of said first electrically conductive substrate;

(c) polymerizing said conductive monomer to form a conducting gel layer comprising conducting polymer polymerized around said biological component;

(d) providing a receptacle containing a sample comprising a target analyte to be analyzed;

(e) contacting said first electrode and second electrode with said sample to be analyzed in said receptacle, whereby the specific binding of the target analyte to biological component results in a measurable electronic charge difference on the surface of said biological component which is transduced to the conducting polymer after applying an effective amount of current or voltage for a sufficient time to said first and second electrically conductive substrates; and

(f) detecting said difference in electronic charge transduced to the conductive polymer.

25. The method according to claim 24, wherein the difference in electronic charge transduced to the conductive polymer is detected by measuring any one of impedance, resistance, capacitance, inductance, current potential, and combinations thereof.

26. The method according to claim 24, wherein the conductive monomer polymerized in step (d) is chosen from the group consisting essentially of copolymers and homopolymers of EDOT, pyrrole, and their functionalized derivatives, polyanilines, salt of polyaniline, polyacetylenes, polythiophenes, a poly(3,4-ethylenedithiathi-ophene), polymer blends thereof, hybrid polymer-metal materials and combinations thereof.

27. The method according to claim 24, wherein said conducting polymer is electrochemically polymerized.

28. The method according to claim 24, wherein the polymerizing and detecting step further comprises connecting the first and second electrically conductive substrates to one or more electrical leads connected to any one of a source of power, galvanostatic current, potentiostatic current or combinations thereof.

29. The method according to claim 24, wherein said step of applying a conducting gel comprising a biological component, said biological component includes one or more of:

a tissue, a cell, a membrane, an organelle, an ion-channel, a lipid bi-layer, a receptor, a receptor fragment, a protein, an enzyme, an antibody, a nucleic acid or a derivatised nucleic acid.

30. The method according to claim 24, wherein said step of applying a conducting gel, said gel further comprises one or more dopants is selected from the group consisting essentially of poly(styrene sulfonate), LiCIO₄, Phosphate-buffered saline, Hank'"'"'s Balanced Salt Solution, Collagen, Poly-D-Lysine, Poly-L-Lysine and poly-ornithine.

31. A biologically integrated bioelectrode device comprising conducting polymer in proximate contact with a first electrically conductive substrate and at least one biological component formed by the steps of:

(a) contacting said biological component with said first electrically conductive substrate, said first electrically conductive substrate chosen from the group consisting essentially of metals, ceramics, carbon, conductive polymers and combinations thereof so as to form a biologically interfaced electrode;

(b) immersing said biologically interfaced electrode in a solution comprising conducting monomer and dopant; and

(c) polymerizing said monomer around said biologically interfaced electrode by inserting a second electrically conductive substrate into said solution of step (b) and applying galvanostatic or potentiostatic current to said first and second electrically conductive substrates for a sufficient time to coat the biologically interfaced electrode with conductive polymer.