Biologically integrated electrode devices

• US 8,005,526 B2
• Filed: 08/30/2006
• Issued: 08/23/2011
• 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: Richardson-Burns, Sarah, Hendricks, Jeffrey L., Abidian, Mohamad Reza, Kim, Donghwan, Povlich, Laura, Meier, Matthew, Martin, David C.
• Primary Examiner(s): Cohen; Lee S
• Application Number:
  US11/512,479
• Publication Number:
  US 20070060815A1
• Time in Patent Office: 1,819 Days
• Field of Search: 600/372, 600/377, 600/378
• 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 and one of said biological component and conductive polymer, said conductive polymer comprising a surface formed by a template biological component, wherein most or all of said template biological component is removed from said surface, and said biological component is coupled to said surface.

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 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.

5. The biologically integrated bioelectrode device according to claim 4, wherein said neural cells comprise neurons.

6. The biologically integrated bioelectrode device according to claim 2, wherein 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, a carbohydrate, and combinations thereof.

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 coupled to the biological component.

15. The biologically integrated bioelectrode device according to claim 14, further comprising an electrical source of power or current operable to communicate with said first and second electrically conductive substrates and the biological component using one or more electrical signals.

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

17. The biologically integrated bioelectrode device according to claim 16, wherein said organic living cell is selected from the group consisting essentially of natural or recombinant eukaryotic cells and prokaryotic cells.

18. The biologically integrated bioelectrode device according to claim 16, wherein 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, a carbohydrate, and combinations thereof.

19. The biologically integrated bioelectrode device according to claim 17, 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.

20. The biologically integrated bioelectrode device according to claim 19, wherein said neural cells comprise neurons.

23. A device comprising a biocompatible and biomimetic coating according to claim 17, wherein said device comprises a microelectrode array, lab on chip device, or target analyte detection device.

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

applying a voltage or current across said first electrically conductive substrate of the bioelectrode device of claim 1 and a second electrically conductive substrate, thereby inducing a voltage or current across said conductive polymer, said second electrically conductive substrate being electrically coupled to said device and a power source; and

detecting the transfer of electrical signals with said bioelectrode device.

25. The method according to claim 24, wherein said biological component is chosen from the group consisting essentially of cardiac cells, neural cells and muscle cells.

26. The method according to claim 24, wherein the detecting step comprises detecting the transfer of electrical signals wherein said signal is selected from the group consisting essentially of impedance, resistance, capacitance, inductance, and current.

27. The method according to claim 24, 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.

28. The method according to claim 27, 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.

21. 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;

a biological component, and

(ii) a conductive polymer comprising a surface formed by a template biological component, wherein most or all of said template biological component is removed from said surface, and said biological component is coupled to said surface.

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

(a) an electrically conductive polymer, and

(b) a biological component,

wherein the electrically conductive polymer comprises a surface formed by a template biological component, wherein most or all of the template biological component is removed from the surface, and the biological component is coupled to the surface.

29. 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 a template 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;

(d) removing most or all of said template biological component from the conductive polymer to expose a surface formed by the template biological component; and

(e) contacting the at least one biological component with said surface to form the biologically integrated bioelectrode device.