Biosensor electrode mediators for regeneration of cofactors

• US 7,504,019 B2
• Filed: 04/26/2004
• Issued: 03/17/2009
• Est. Priority Date: 10/16/1997
• Status: Expired due to Fees

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Laboratories
• Inventors: Forrow, Nigel J., Watkin, Jared L., Sanghera, Gurdial S., Walters, Stephen
• Primary Examiner(s): Olsen; Kaj K
• Application Number:
  US10/832,408
• Publication Number:
  US 20040197935A1
• Time in Patent Office: 1,786 Days
• Field of Search: 204/403.01, 204/403.02, 204/403.04, 204/403.12, 205/777.5, 205/792
• US Class Current: 205/777.5
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: Y10T 29/49155 Manufacturing circuit on or in base

Abstract

The present invention is based on the discovery of NAD⁺ and NADP⁺ mediator compounds that do not bind irreversibly to thiol groups in the active sites of intracellular dehydrogenase enzymes. Such mediator compounds avoid a common mode of enzyme inhibition. The mediators can therefore increase the stability and reliability of the electrical response in amperometric electrodes constructed from NAD- or NADP-dependent enzymes.

Claims

1. A single use disposable electrode strip for attachment to the signal readout circuitry of a sensor system to detect a current representative of an analyte in an aqueous sample, the strip comprising:

a) an elongated support having a substantially flat, planar surface, adapted for releasable attachment to said readout circuitry;

b) a first conductor extending along said surface and comprising a conductive element for connection to said readout circuitry;

an active electrode on said surface in contact with said first conductor, said active electrode comprising a nicotinamide co-factor-dependent enzyme, a nicotinamide cofactor, and a mediator consisting of a compound having the following formula;

2. The electrode strip of claim 1 wherein the cofactor-dependent enzyme is 3-Hydroxybutyrate Dehydrogenase.

3. A process of measuring the concentration in an aqueous sample of an analyte subject to oxidation by a NAD(P)⁺ dependent enzyme comprising:

a) providing the electrode strip of claim 1;

b) applying the sample containing the analyte to the electrode strip;

c) detecting the sample applied to the electrode strip;

d) oxidizing the analyte with the NAD(P)⁺dependent enzyme in the presence of NAD(P)⁺;

oxidizing the NAD(P)H generated by reaction with the analyte and NAD(P)⁺ dependent enzyme with the mediator compound of step a); and

e) applying an electrical potential at an electrode to reoxidize the mediator compound reduced in oxidizing NAD(P)H and observing the resultant current.

4. The process of claim 3 wherein the NAD(P)⁺ dependent enzyme, NAD(P)⁺, and mediator compound have been applied to the surface of said electrode in combination with a binder and a filler.

5. The process of claim 4 wherein the current observed during the measurement period is linearly related to the concentration of the analyte in the sample.

6. The process of claim 3 wherein the applied potential is 200 mV or less.

7. The process of claim 3, wherein the current is linearly related to the concentration of the analyte.

8. The electrode strip of claim 1, further including a dummy electrode.

9. The electrode strip of claim 1, further including circuit loops for providing a resistance characteristic of the electrode strip to identify the electrode strip as being suitable for a particular analyte.

10. The electrode strip of claim 1, further including at least one notch or other shape in an end of the test strip to identify the electrode strip as being suitable for a particular analyte.

11. The electrode strip of claim 1, further including at least one strip identifier, the strip identifier being arranged and configured to be detected by a switch of a meter to identify the electrode strip as being suitable for a particular analyte.

12. The electrode strip of claim 1, further including at least one strip identifier, the strip identifier being arranged and configured to be detected by an optical detector of a meter to identify the electrode strip as being suitable for a particular analyte.

13. A single use disposable electrode strip for attachment to the signal readout circuitry of a sensor system to detect a current representative of an analyte in an aqueous sample, the strip comprising:

a) an elongated support having a substantially flat, planar surface, adapted for releasable attachment to said readout circuitry;

b) a first conductor extending along said surface and comprising a conductive element for connection to said readout circuitry;

c) an active electrode on said surface in contact with said first conductor;

said active electrode comprising a nicotinamide co-factor-dependent enzyme, a nicotinamide cofactor, and a mediator consisting of a compound having the following formula;

14. The electrode strip of claim 13 wherein the mediator compound is 1,10-phenanthroline quinone.

15. The electrode strip of claim 14 wherein the cofactor-dependent enzyme is Glucose Dehydrogenase.

16. The electrode strip of claim 13, further including circuit loops for providing a resistance characteristic of the electrode strip to identify the electrode strip as being suitable for a particular analyte.

17. The electrode strip of claim 13, further including at least one notch or other shape in an end of the electrode strip to identify the electrode strip as being suitable for a particular analyte.

18. The electrode strip of claim 13, further including at least one strip identifier, the strip identifier being arranged and configured to be detected by a switch of a meter to identify the electrode strip as being suitable for a particular analyte.

19. The electrode strip of claim 13, further including at least one strip identifier, the strip identifier being arranged and configured to be detected by an optical detector of a meter to identify the electrode strip as being suitable for a particular analyte.

20. A process of measuring the concentration in an aqueous sample of an analyte subject to oxidation by a NAD(P)⁺ dependent enzyme comprising:

a) providing the electrode strip of claim 13;

b) applying the sample containing the analyte to the electrode strip;

c) detecting the sample applied to the electrode strip;

d) oxidizing the analyte with the NAD(P)⁺ dependent enzyme in the presence of NAD(P)⁺;

oxidizing the NAD(P)H generated by reaction with the analyte and NAD(P)⁺ dependent enzyme with the mediator compound of step a); and

e) applying an electrical potential at an electrode to reoxidize the mediator compound reduced in oxidizing NAD(P)H and observing the resultant current.

21. The process of claim 20 wherein the mediator is 1,10-phenanthroline quinone.

22. The process of claim 21 wherein the cofactor-dependent enzyme is Glucose Dehydrogenase.

23. The process of claim 21 wherein the cofactor dependent enzyme is 3-Hydroxybutyrate Dehydrogenase.