Reference electrodes having an extended lifetime for use in long term amperometric sensors

• US 8,155,722 B2
• Filed: 06/02/2008
• Issued: 04/10/2012
• Est. Priority Date: 06/02/2008
• Status: Active Grant

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Inventors: Feldman, Benjamin J., Liu, Zenghe, Ouyang, Tianmei
• Primary Examiner(s): Yu, Melanie J
• Application Number:
  US12/131,862
• Publication Number:
  US 20090294301A1
• Time in Patent Office: 1,408 Days
• Field of Search: 600/345, 600/372, 600/309
• US Class Current: 600/345
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

The present application provides Ag/AgCl based reference electrodes having an extended lifetime that are suitable for use in long term amperometric sensors. Electrochemical sensors equipped with reference electrodes described herein demonstrate considerable stability and extended lifetime in a variety of conditions.

Claims

1. A reference electrode for use in electrochemical sensor, comprising:

a layer of Ag/AgCl having a lateral surface and a layer of permselective coating consisting of poly(vinylpyridine-co-styrene) disposed over the lateral surface of the layer of Ag/AgCl to limit dissolution of the layer of Ag/AgCl.

2. The reference electrode of claim 1, wherein the permselective coating comprises poly(2-vinylpyridine-co-styrene).

3. The reference electrode of claim 1, wherein the permselective coating comprises poly(4-vinylpyridine-co-styrene).

4. The reference electrode of claim 1, wherein at least a portion of the reference electrode is adapted to be subcutaneously positioned in a subject.

24. The reference electrode of claim 1, wherein the reference electrode further comprises a flux limiting layer disposed on top of the permselective coating.

25. The reference electrode of claim 1, wherein the poly(vinylpyridine-co-styrene) comprises from 5% to 20% loading of styrene.

5. An electrochemical sensor, comprising:

a working electrode comprising a sensing layer in contact with a conductive material of the electrode and a membrane disposed over the sensing layer; and

a reference electrode comprising a layer of Ag/AgCl having a lateral surface and a layer of permselective coating consisting of poly(vinylpyridine-co-styrene) disposed over the lateral surface of the layer of Ag/AgCl to limit dissolution of the layer of Ag/AgCl,

wherein the reference electrode is in electrochemical communication with the working electrode.

6. The electrochemical sensor of claim 5, wherein the permselective coating comprises poly(2-vinylpyridine-co-styrene).

7. The electrochemical sensor of claim 5, wherein the permselective coating comprises poly(4-vinylpyridine-co-styrene).

8. The electrochemical sensor of claim 5, wherein the sensing layer of the working electrode comprises a glucose-responsive enzyme.

9. The electrochemical sensor of claim 5, wherein the sensing layer of the working electrode comprises a redox mediator.

10. The electrochemical sensor of claim 9, wherein the redox mediator comprises a complex selected from the group consisting of a ruthenium-containing complex and an osmium-containing complex.

11. The electrochemical sensor of claim 9, wherein the redox mediator is non-leachable with respect to the working electrode.

12. The electrochemical sensor of claim 9, wherein the redox mediator is immobilized on the working electrode.

13. The electrochemical sensor of claim 5, wherein at least a portion of the electrochemical sensor is adapted to be subcutaneously positioned in a subject.

26. The electrochemical sensor of claim 5, wherein the electrochemical sensor further comprises a flux limiting layer disposed on top of the permselective coating.

27. The electrochemical sensor of claim 5, wherein the poly(vinylpyridine-co-styrene) comprises from 5% to 20% loading of styrene.

14. An analyte sensor assembly, comprising:

an electrochemical sensor comprising a flexible substrate comprising

(i) at least one working electrode comprising a sensing layer and a membrane disposed over the sensing layer,

(ii) at least one reference electrode comprising a layer of Ag/AgCl having a lateral surface and a layer of permselective coating consisting of poly(vinylpyridine-co-styrene) disposed over the lateral surface of the layer of Ag/AgCl to limit dissolution of the layer of Ag/AgCl,

(iii) at least one contact pad coupled to each of the working and reference electrodes,

wherein the electrochemical sensor is adapted for implantation of a portion of the electrochemical sensor comprising the working and reference electrodes through skin; and

an electrochemical sensor control unit comprising

(i) a housing adapted for placement on skin;

(ii) a plurality of conductive contacts disposed on the housing and configured for coupling to the contact pads of the electrochemical sensor; and

(iii) an rf transmitter disposed in the housing and coupled to the plurality of conductive contacts for transmitting data obtained using the electrochemical sensor.

15. The analyte sensor assembly of claim 14, wherein the permselective coating comprises poly(2-vinylpyridine-co-styrene).

16. The analyte sensor assembly of claim 14, wherein the permselective coating comprises poly(4-vinylpyridine-co-styrene).

17. The analyte sensor assembly of claim 14, wherein the sensing layer of the working electrode comprises a glucose-responsive enzyme.

18. The analyte sensor assembly of claim 14, wherein the sensing layer of the working electrode comprises a redox mediator.

19. The analyte sensor assembly of claim 14, wherein the redox mediator comprises a complex selected from the group consisting of a ruthenium-containing complex and an osmium-containing complex.

20. The analyte sensor assembly of claim 18, wherein the redox mediator is non-leachable with respect to the working electrode.

21. The analyte sensor assembly of claim 18, wherein the redox mediator is immobilized on the working electrode.

22. The analyte sensor assembly of claim 14, wherein the membrane limits flux of glucose or lactate thereacross.

23. The analyte sensor assembly of claim 14, wherein the membrane limits flux of glucose or lactose thereacross in vivo.

28. The analyte sensor assembly of claim 14, wherein the electrochemical sensor further comprises a flux limiting layer disposed on top of the permselective coating.

29. The analyte sensor assembly of claim 14, wherein the poly(vinylpyridine-co-styrene) comprises from 5% to 20% loading of styrene.