Small volume in vitro analyte sensor

• US 8,142,643 B2
• Filed: 09/29/2009
• Issued: 03/27/2012
• Est. Priority Date: 02/06/1997
• Status: Expired due to Fees

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Heller, Adam, Feldman, Benjamin J., Say, James, Vreeke, Mark S.
• Primary Examiner(s): Noguerola, Alex
• Application Number:
  US12/568,858
• Publication Number:
  US 20100018868A1
• Time in Patent Office: 910 Days
• Field of Search: 20440301-40315, 205/777.5, 205/778, 205/792
• US Class Current: 205/792
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157 disposable multilayered or laminated electrodes G01N27/307; details of handling chemical test elements G01N33/4875
• CPC Class Codes: A61B 5/1411 by percutaneous method, e.g. by lancet
• 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 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• 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: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150358 Strips for collecting blood, e.g. absorbent optical reagent test strips G01N21/8483; chemical reagent test strips G01N33/4875, G01N33/52
• CPC Class Codes: A61B 5/150412 Pointed piercing elements, e.g. needles, lancets for piercing the skin blade-like piercing elements A61B5/150442
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/15105 Purely manual piercing, i.e. the user pierces the skin without the assistance of any driving means or driving devices
• CPC Class Codes: A61B 5/15113 Manually triggered, i.e. the triggering requires a deliberate action by the user such as pressing a drive button
• CPC Class Codes: A61B 5/15144 comprising driving means, e.g. a spring, for retracting the piercing unit into the housing
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 2333/904 acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
• 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 33/5438 : Electrodes

Abstract

A sensor designed to determine the amount and concentration of analyte in a sample having a volume of less than about 1 μL. The sensor has a working electrode coated with a non-leachable redox mediator. The redox mediator acts as an electron transfer agent between the analyte and the electrode. In addition, a second electron transfer agent, such as an enzyme, can be added to facilitate the electrooxidation or electroreduction of the analyte. The redox mediator is typically a redox compound bound to a polymer. The preferred redox mediators are air-oxidizable.

The amount of analyte can be determined by coulometry. One particular coulometric technique includes the measurement of the current between the working electrode and a counter or reference electrode at two or more times. The charge passed by this current to or from the analyte is correlated with the amount of analyte in the sample. Other electrochemical detection methods, such as amperometric, voltammetric, and potentiometric techniques, can also be used.

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. An enzyme capable of catalyzing the electrooxidation or electroreduction of the biomolecule is provided as a second electron transfer agent.

Claims

1. A method for determining a concentration of an analyte in a body fluid of a patient, comprising the steps of:

creating a flow of a body fluid from forearm skin of a patient;

transporting no more than 1000 nl of the body fluid into an analyte sensor comprising a sample chamber, the sample chamber having a volume of no more than 1000 nl and comprising a redox mediator and at least two electrodes including a working electrode and a reference and/or counter electrode, wherein said sensor is configured and arranged for determining the concentration of the analyte from no more than 1000 nL of body fluid;

holding the sample within the sample chamber in a non-flow-through manner; and

determining by coulometry the concentration of the analyte in the body fluid.

2. The method of claim 1, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from no more than 500 nL of body fluid.

3. The method of claim 1, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from no more than 200 nL of body fluid.

4. The method of claim 1, wherein the sample chamber has a volume of no more than 200 nL.

5. The method of claim 1, wherein the sample chamber has a volume of no more than 100 nL.

6. The method of claim 1, wherein creating a flow of a body fluid comprises piercing a portion of the skin of the patient to cause a flow of a body fluid from the patient.

7. The method of claim 1, wherein the analyte sensor is configured and arranged for determining a concentration of the analyte from no more than 100 nL of the body fluid.

8. The method of claim 1, wherein creating a flow of a body fluid comprises creating a flow of no more than 1000 nL of a body fluid from the patient.

9. The method of claim 1, wherein creating a flow of a body fluid comprises creating a flow of no more than 500 nL of a body fluid from the patient.

10. The method of claim 1, wherein creating a flow of a body fluid comprises creating a flow of no more than 200 nL of a body fluid from the patient.

11. The method of claim 1, wherein the working electrode and the reference or counter electrode are a facing electrode pair.

12. The method of claim 1, wherein the sensor further includes a non-leachable enzyme on the working electrode.

13. The method of claim 12, wherein the enzyme is immobilized on the working electrode.

14. The method of claim 1, wherein the redox mediator is non-leachable.

15. The method of claim 14, wherein the redox mediator is immobilized on the working electrode.

16. The method of claim 1, wherein the body fluid comprises blood.

17. The method of claim 1, wherein the body fluid consists essentially of blood.

18. The method of claim 1, wherein the analyte is glucose.

19. The method of claim 1, wherein transporting the body fluid into an analyte sensor comprises transporting, by wicking with a sorbent material disposed in the sample chamber, the body fluid into the analyte sensor.

20. The method of claim 1, wherein transporting the body fluid into an analyte sensor comprises transporting, by capillary action, a portion of the body fluid into a sample chamber of the analyte sensor.

21. The method of claim 1, wherein transporting the body fluid into an analyte sensor comprises transporting, by application of a vacuum, a portion of the body fluid into a sample chamber of the analyte sensor.

22. The method of claim 1, wherein the sample chamber has a volume of no more than 500 nL.

23. The method of claim 1, wherein transporting the body fluid comprises transporting no more than 500 nL of the body fluid into the analyte sensor.

24. The method of claim 1, wherein transporting the body fluid comprises transporting no more than 200 nL of the body fluid into the analyte sensor.

25. The method of claim 1, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 200 microns.

26. The method of claim 1, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 100 microns.

27. The method of claim 1, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 50 microns.

28. The method of claim 1, wherein the analyte sensor comprises glucose oxidase or glucose dehydrogenase.

29. The method of claim 1, wherein the redox mediator comprises an osmium complex, a ferrocyanide, or a ferricyanide.

30. The method of claim 1, wherein the working electrode is constructed of a material selected from gold, carbon, platinum, ruthenium dioxide and palladium.

31. A method for determining a concentration of an analyte in a body fluid of a patient, comprising the steps of:

creating a flow of a body fluid from forearm skin of a patient;

transporting no more than 1000 nl the body fluid into an analyte sensor comprising a sample chamber, the sample chamber having a volume of no more than 1000 nl and comprising a redox mediator and at least two electrodes including a working electrode and a reference and/or counter electrode separated by a distance of no greater than 1000 microns, wherein said sensor is configured and arranged for determining the concentration of the analyte from no more than 1000 nL of body fluid;

holding the sample within the sample chamber in a non-flow-through manner; and

determining by coulometry the concentration of the analyte in the body fluid.

32. The method of claim 31, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 200 microns.

33. The method of claim 31, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 100 microns.

34. The method of claim 31, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 50 microns.

35. The method of claim 31, wherein the working electrode and the reference or counter electrode are a facing electrode pair.

36. The method of claim 31, wherein the electrodes are disposed in a coplanar configuration.

37. The method of claim 31, wherein transporting the body fluid comprises transporting no more than 500 nL of the body fluid into the analyte sensor.

38. The method of claim 31, wherein transporting the body fluid comprises transporting no more than 200 nL of the body fluid into the analyte sensor.

39. The method of claim 31, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from no more than 500 nL body fluid.

40. The method of claim 31, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from no more than 200 nL of body fluid.

41. The method of claim 31, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from no more than 100 nL of body fluid.

42. The method of claim 31, wherein the sample chamber has a volume of no more than 500 nL.

43. The method of claim 31, wherein the sample chamber has a volume of no more than 200 nL.

44. The method of claim 31, wherein the sample chamber has a volume of no more than 100 nL.

45. The method of claim 31, wherein creating a flow of a body fluid comprises creating a flow of no more than 1000 nL of a body fluid from the patient.

46. The method of claim 31, wherein creating a flow of a body fluid comprises creating a flow of no more than 500 nL of a body fluid from the patient.

47. The method of claim 31, wherein creating a flow of a body fluid comprises creating a flow of no more than 200 nL of a body fluid from the patient.

48. The method of claim 31, wherein the redox mediator is non-leachable.

49. The method of claim 31, wherein the redox mediator is immobilized on the working electrode.

50. The method of claim 31, wherein glucose dehydrogenase or glucose oxidase is deposited on the working electrode.

51. The method of claim 31, wherein the body fluid comprises blood.

52. The method of claim 31, wherein the body fluid consists essentially of blood.

53. The method of claim 31, wherein the redox mediator comprises an osmium complex, a ferrocyanide, or a ferricyanide.

54. The method of claim 31, wherein the working electrode is constructed of a material selected from gold, carbon, platinum, ruthenium dioxide and palladium.

55. A method for determining a concentration of an analyte in a body fluid of a patient, comprising the steps of:

creating a flow of a body fluid from forearm skin of a patient;

transporting no more than 1000 nl of the body fluid into an analyte sensor comprising a sample chamber, the sample chamber having a volume of no more than 1000 nl and comprising a redox mediator and at least two electrodes including a working electrode and a reference and/or counter electrode disposed in a coplanar configuration, wherein said sensor is configured and arranged for determining the concentration of the analyte from no more than 1000 nL of body fluid;

holding the sample within the sample chamber in a non-flow-through manner; and

determining by coulometry the concentration of the analyte in the body fluid.

56. The method of claim 55, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 1000 microns.

57. The method of claim 55, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 200 microns.

58. The method of claim 55, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 100 microns.

59. The method of claim 55, wherein the distance between the working electrode and the reference and/or counter electrode is no greater than 50 microns.

60. The method of claim 55, wherein transporting the body fluid comprises transporting no more than 500 nL of the body fluid into the analyte sensor.

61. The method of claim 55, wherein transporting the body fluid comprises transporting no more than 200 nL of the body fluid into the analyte sensor.

62. The method of claim 55, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from no more than 500 nL of body fluid.

63. The method of claim 55, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from no more than 200 nL of body fluid.

64. The method of claim 55, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from no more than 100 nL of body fluid.

65. The method of claim 55, wherein the sample chamber has a volume of no more than 500 nL.

66. The method of claim 55, wherein the sample chamber has a volume of no more than 200 nL.

67. The method of claim 55, wherein the sample chamber has a volume of no more than 100 nL.

68. The method of claim 55, wherein creating a flow of a body fluid comprises creating a flow of no more than 1000 nL of a body fluid from the patient.

69. The method of claim 55, wherein creating a flow of a body fluid comprises creating a flow of no more than 500 nL of a body fluid from the patient.

70. The method of claim 55, wherein creating a flow of a body fluid comprises creating a flow of no more than 200 nL of a body fluid from the patient.

71. The method of claim 55, wherein the redox mediator is non-leachable.

72. The method of claim 55, wherein the redox mediator is immobilized on the working electrode.

73. The method of claim 55, wherein glucose dehydrogenase or glucose oxidase is deposited on the working electrode.

74. The method of claim 55, wherein the body fluid comprises blood.

75. The method of claim 55, wherein the body fluid consists essentially of blood.

76. The method of claim 55, wherein the redox mediator comprises an osmium complex, a ferrocyanide, or a ferricyanide.

77. The method of claim 55, wherein the working electrode is constructed of a material selected from gold, carbon, platinum, ruthenium dioxide and palladium.