Small volume in vitro analyte sensor and methods of making

• US 8,273,241 B2
• Filed: 09/29/2009
• Issued: 09/25/2012
• Est. Priority Date: 10/08/1998
• Status: Expired due to Fees

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Inventors: Feldman, Benjamin J., Heller, Adam, Heller, Ephraim, Mao, Fei, Vivolo, Joseph A., Funderburk, Jeffery V., Colman, Fredric C., Krishnan, Rajesh
• Primary Examiner(s): Noguerola, Alex
• Application Number:
  US12/569,369
• Publication Number:
  US 20100012525A1
• Time in Patent Office: 1,092 Days
• Field of Search: 20440301-40315, 205/777.5, 205/778, 205/792
• US Class Current: 205/777.5
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: C12Q 1/32 involving dehydrogenase
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• 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: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: Y10T 156/1052 with cutting, punching, tearing or severing
• CPC Class Codes: Y10T 29/49002 Electrical device making
• CPC Class Codes: Y10T 29/49004 including measuring or testing of device or component part
• CPC Class Codes: Y10T 29/49007 Indicating transducer
• CPC Class Codes: Y10T 29/49126 Assembling bases
• CPC Class Codes: Y10T 29/49128 Assembling formed circuit to base
• CPC Class Codes: Y10T 29/4913 Assembling to base an electrical component, e.g., capacitor, etc.
• CPC Class Codes: Y10T 29/49147 Assembling terminal to base
• CPC Class Codes: Y10T 29/49155 Manufacturing circuit on or in base
• CPC Class Codes: Y10T 29/49204 Contact or terminal manufacturing
• CPC Class Codes: Y10T 29/49208 by assembling plural parts
• CPC Class Codes: Y10T 29/4921 with bonding
• CPC Class Codes: Y10T 29/49794 Dividing on common outline

Abstract

A sensor utilizing a non-leachable or diffusible redox mediator is described. The sensor includes a sample chamber to hold a sample in electrolytic contact with a working electrode, and in at least some instances, the sensor also contains a non-leachable or a diffusible second electron transfer agent. The sensor and/or the methods used produce a sensor signal in response to the analyte that can be distinguished from a background signal caused by the mediator. The invention can be used to determine the concentration of a biomolecule, such as glucose or lactate, in a biological fluid, such as blood or serum, using techniques such as coulometry, amperometry; and potentiometry. An enzyme capable of catalyzing the electrooxidation or electroreduction of the biomolecule is typically provided as a second electron transfer agent.

Claims

1. A sensor for determining the concentration of an analyte in a sample fluid, the sensor comprising:

a working electrode;

a counter electrode; and

an analyte-responsive enzyme and a redox mediator disposed on the working electrode, wherein the redox mediator comprises;

a transition metal selected from the group consisting of osmium, ruthenium, iron, and cobalt;

two or more ligands coordinately bound to the transition metal, wherein at least one of the ligands is a heterocyclic nitrogen-containing bidentate ligand comprising

2. The sensor of claim 1, wherein the transition metal is osmium.

3. The sensor of claim 1, wherein R₁ is an alkyl.

4. The sensor of claim 3, wherein R₁ is methyl.

5. The sensor of claim 1, wherein at least one of the ligands is a unsubstituted or substituted pyridine.

6. The sensor of claim 1, wherein at least one of the ligands is a monosubstituted pyridine.

7. The sensor of claim 6, wherein the monosubstituted pyridine is a monoaminopyridine.

8. The sensor of claim 1, wherein at least one of the ligands is a halogen selected from the group consisting of fluorine, chlorine, and bromine.

9. The sensor of claim 8, wherein the halogen is chlorine.

10. The sensor of claim 1, wherein at least one of the ligands is a heterocyclic nitrogen-containing bidentate ligand comprising

11. The sensor of claim 10, wherein R₂ and R₃ are independently selected from hydrogen and alkyl.

12. The sensor of claim 11, wherein R₂ and R₃ are independently selected from hydrogen and methyl.

13. The sensor of claim 1, wherein the analyte is glucose.

14. The sensor of claim 13, wherein the analyte-responsive enzyme is a glucose dehydrogenase.

15. The sensor of claim 1, wherein the working electrode and the counter electrode are separated by an effective distance in a range of 25 to 1000 μ

m.

16. A method for determining a concentration of an analyte in a sample fluid, comprising the steps of:

contacting a sample fluid with a sensor, wherein the sensor comprises;

a working electrode;

a counter electrode; and

an analyte-responsive enzyme and a redox mediator disposed on the working electrode, wherein the redox mediator comprises;

a transition metal selected from the group consisting of osmium, ruthenium, iron, and cobalt;

two or more ligands coordinately bound to the transition metal, wherein at least one of the ligands is a heterocyclic nitrogen-containing bidentate ligand comprising

17. The method according to claim 16, wherein determining the concentration of the analyte using the sensor signal comprises determining the concentration of the analyte using coulometry, amperometry or potentiometry.

18. The method according to claim 16, wherein the transition metal is osmium.

19. The method according to claim 16, wherein R₁ is an alkyl.

20. The method according to claim 19, wherein R₁ is methyl.

21. The method according to claim 16, wherein at least one of the ligands is a unsubstituted or substituted pyridine.

22. The method according to claim 21, wherein at least one of the ligands is a monosubstituted pyridine.

23. The method according to claim 22, wherein the monosubstituted pyridine is a monoaminopyridine.

24. The method according to claim 16, wherein at least one of the ligands is a halogen selected from the group consisting of fluorine, chlorine, and bromine.

25. The method according to claim 24, wherein the halogen is chlorine.

26. The method according to claim 16, wherein at least one of the ligands is a heterocyclic nitrogen-containing bidentate ligand comprising

27. The method according to claim 26, wherein R₂ and R₃ are independently selected from hydrogen and alkyl.

28. The method according to claim 27, wherein R₂ and R₃ are independently selected from hydrogen and methyl.

29. The method according to claim 16, wherein the analyte is glucose.

30. The method according to claim 29, wherein the analyte-responsive enzyme is a glucose dehydrogenase.

31. The method according to claim 16, wherein the working electrode and the counter electrode are separated by an effective distance in a range of 25 to 1000 μ

m.

32. An electrode comprising a redox mediator disposed on the electrode, wherein the redox mediator comprises:

osmium; and

two or more ligands coordinately bound to the osmium, wherein at least one of the ligands is a heterocyclic nitrogen-containing bidentate ligand comprising

33. The electrode of claim 32, wherein R₁ is an alkyl.

34. The electrode of claim 33, wherein R₁ is methyl.

35. The electrode of claim 32, wherein at least one of the ligands is a unsubstituted or substituted pyridine.

36. The electrode of claim 35, wherein at least one of the ligands is a monosubstituted pyridine.

37. The electrode of claim 36, wherein the monosubstituted pyridine is a monoaminopyridine.

38. The electrode of claim 32, wherein at least one of the ligands is a halogen selected from the group consisting of fluorine, chlorine, and bromine.

39. The electrode of claim 38, wherein the halogen is chlorine.

40. The electrode of claim 32, wherein at least one of the ligands is a heterocyclic nitrogen-containing bidentate ligand comprising

41. The electrode of claim 40, wherein R₂ and R₃ are independently selected from hydrogen and alkyl.

42. The electrode of claim 41, wherein R₂ and R₃ are independently selected from hydrogen and methyl.

43. The electrode of claim 32, further comprising an analyte-responsive enzyme.

44. The electrode of claim 43, wherein the analyte-responsive enzyme is a glucose dehydrogenase.