Electrodes, methods, apparatuses comprising micro-electrode arrays

• US 20030116447A1
• Filed: 10/04/2002
• Published: 06/26/2003
• Est. Priority Date: 11/16/2001
• Status: Abandoned Application

• Current Assignee: Corange International Limited (Roche Holding AG)
• Original Assignee: Corange International Limited (Roche Holding AG)
• Inventors: Wilsey, Christopher D., Surridge, Nigel A.
• Application Number:
  US10/264,785
• Publication Number:
  US 20030116447A1
• Time in Patent Office: Days
• 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: G01N 27/307 Disposable laminated or multilayered electrodes G01N27/3272 takes precedence
• 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 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875
• CPC Class Codes: G01N 27/3275 Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction

Abstract

Described are micro-arrays of electrodes disposed proximal to a flexible substrate, electronic components and sensors comprising such arrays, and methods of use for such arrays.

Claims

1. A disposable electrochemical sensor for the detection of an analyte in a liquid sample comprising a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, said reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte, wherein the sample-receiving cavity has a volume of less that 1.0 μ

l and wherein the sensor provides an accurate reading of the amount of analyte in a period of 10 seconds or less.

2. The sensor of claim 1, wherein the reagent layer further comprises an electron transfer mediator.

3. The sensor of claim 2 in which the mediator is selected from the group consisting of ferricyanide, osmium (III)-(bipyridyl)-2-imidazolyl-chloride, Meldola blue, [Ru(NH₃)₅pyz]₂(SO₄)₃, and nitrosoanaline derivatives.

4. The sensor of claim 3, wherein the mediator is nitrosoanaline derivatives.

5. The sensor of claim 3, wherein the mediator is ferricyanide.

6. The sensor of claim 2 in which the analyte is selected from the group consisting of glucose, cholesterol, HDL cholesterol, triglycerides, lactate, lactate dehydrogenase, pyruvate, alcohol, uric acid, and 3-Hydroxybutyric acid

7. The sensor of claim 6, wherein the analyte is glucose.

8. The sensor of claim 7 in which the mediator is selected from the group consisting of ferricyanide, osmium (III)-(bipyridyl)-2-imidazolyl-chloride, Meldola blue, [Ru(NH₃)₅pyz]₂(SO₄)₃, and nitrosoanaline derivatives.

9. The sensor of claim 8, wherein the mediator is ferricyanide.

10. The sensor of claim 7 in which the enzyme is selected from the group consisting of glucose oxidase, glucose dehydrogenase and diaphorase.

11. The sensor of claim 10 in which the enzyme is glucose dehydrogenase.

12. The sensor of claim 10 in which the enzyme is glucose oxidase.

13. The sensor of claim 10 in which the mediator is selected from the group consisting of ferricyanide, osmium (III)-(bipyridyl)-2-imidazolyl-chloride, Meldola blue, [Ru(NH₃)₅pyz]₂(SO₄)₃, and nitrosoanaline derivatives.

14. The sensor of claim 13, wherein the mediator is ferricyanide.

15. The sensor of claim 1, wherein the reagent layer is disposed over both the working electrode and the reference electrode.

16. The sensor of claim 1, wherein both the working electrode and the reference electrode are conductive carbon electrodes.

17. A method of determining the concentration of an analyte in a liquid sample comprising:

providing a test sensor including a sample receiving cavity having a volume of less than 1 μ

l, the sensor including working and counter electrodes disposed within the sample receiving cavity, the sensor further including a reagent layer comprising an enzyme and a mediator, the reagent layer being disposed on at least the working electrode, the enzyme and mediator being selected to react with the analyte to generate an electrochemical signal representative of the concentration of the analyte in the liquid sample;

admitting the liquid sample into the sample receiving cavity;

detecting the time at which the liquid sample enters the sample cavity;

following said detecting, controlling the voltage or current across the working and counter electrodes; and

within ten seconds of said detecting, obtaining a readout of the concentration of the analyte in the liquid sample.

18. The method of claim 17 in which said obtaining comprises measuring the electrochemical signal received from the working electrode and determining the concentration of the analyte from the electrochemical signal.

19. The method of claim 17 in which said controlling comprises applying a DC voltage of 100-500 mV across the working and counter electrodes, said obtaining comprising measuring the current received from the working electrode and determining the concentration of the analyte from the measured current.

20. A disposable electrochemical sensor for the detection of an analyte in a liquid sample comprising a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, said reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte, wherein the sample-receiving cavity has a volume of less than about 0.4 μ

l, and wherein the sensor provides an accurate reading of the amount of analyte in a period of 10 seconds or less.

21. The sensor of claim 20 in which the sample receiving cavity has a volume of about 0.1 μ

l to about 0.4 μ

l.

22. The sensor of claim 21 in which the sample receiving cavity has a volume of about 0.1 to about 0.25 μ

l.

23. The sensor of claim 20 in which the sample receiving cavity has a height of about 25 to about 200 μ

m.

24. The sensor of claim 20 in which the sample-receiving cavity has a width of about 1 mm.

25. The sensor of claim 20 in which the sample-receiving cavity has a length of about 4 mm.

26. The sensor of claim 20 in which the gap between the working and reference electrodes is 15 μ

m to 50 μ

m.

27. The sensor of claim 20 in which each of the working and reference electrodes has a thickness of 10 μ

m to 200 μ

m.

30. A method for detecting the concentration of an analyte in a liquid sample comprising:

providing a disposable electrochemical sensor including a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, the reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte, the sample-receiving cavity having a volume of less than about 1 μ

l;

admitting the liquid sample into the sample chamber;

detecting the application time at which the liquid sample enters the sample chamber;

following said application time, applying a voltage across the working and reference electrodes; and

within ten seconds of said application time, obtaining a readout of the concentration of the analyte in the liquid sample.

31. The method of claim 30 in which the sample-receiving cavity has a volume of less than about 0.4 μ

l.

32. The sensor of claim 31 in which the sample receiving cavity has a volume of about 0.1 μ

l to about 0.4 μ

l.

33. The sensor of claim 32 in which the sample receiving cavity has a volume of about 0.1 to about 0.25 μ

l.

34. The sensor of claim 30 in which the sample receiving cavity has a height of about 25 to about 200 μ

m.

35. The method of claim 30 which includes incubating the liquid sample for an incubation time extending from the application time to said applying a voltage.

36. The method of claim 35 in which the incubation time is from about 0.5 seconds to about 6 seconds.

37. The method of claim 36 in which the incubation time is about 2 seconds to about 6 seconds.

38. The method of claim 37 in which the incubation time is about 3 seconds.

39. The method of claim 36 in which the incubation time is about 0.5 seconds.

40. The method of claim 30 in which said obtaining a readout comprises obtaining the readout in a test time from about 0.5 to about 2 seconds after said applying a voltage.

41. The method of claim 40 in which the test time is 0.5 to 1.5 seconds.

42. The method of claim 30 in which said obtaining a readout comprises obtaining the readout less than about 5 seconds after the application time.

43. The method of claim 42 in which said obtaining a readout comprises obtaining the readout about 4 seconds after the application time.

44. The method of claim 30 in which said applying a voltage comprises applying a voltage of about 100 mV to about 500 mV.

45. The method of claim 44 in which said applying a voltage comprises applying a voltage of about 300 mV.

46. A disposable electrochemical sensor for the detection of an analyte in a liquid sample comprising a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, said reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte, wherein the sample-receiving cavity has a height of about 25 μ

m to about 200 μ

m, and wherein the sensor provides an accurate reading of the amount of analyte in a period of 10 seconds or less.

47. The sensor of claim 46 in which the sample receiving cavity has a height of about 25 μ

m to about 100 μ

m.

48. The sensor of claim 46 in which the sample receiving cavity has a height of at least about 100 μ

m.

49. The sensor of claim 48 in which the sample receiving cavity has a height of about 125 μ

m.

50. The sensor of claim 46 in which the sample receiving cavity has a volume of less than about 1 μ

l.

51. The sensor of claim 50 in which the sample receiving cavity has a volume of about 0.1 to about 0.4 μ

l.

52. A method for determining the concentration of an analyte in a liquid sample comprising

providing a disposable electrochemical sensor comprising a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, the reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte;

admitting the liquid sample into the sample receiving cavity;

detecting the application time at which the liquid sample enters the sample chamber;

following said application time, applying a voltage across the working and reference electrodes for a time of less than about 2 seconds; and

within ten seconds of said application time, obtaining a readout of the concentration of the analyte in the liquid sample.

53. The method of claim 52 in which said applying a voltage comprises applying a voltage for a time from about 0.5 to about 2 seconds.