Small volume in vitro analyte sensor

• US 8,142,642 B2
• Filed: 07/30/2008
• Issued: 03/27/2012
• Est. Priority Date: 02/06/1997
• Status: Expired due to Fees

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Inventors: Heller, Adam, Feldman, Benjamin J., Say, James, Vreeke, Mark S.
• Primary Examiner(s): Noguerola, Alex
• Application Number:
  US12/182,862
• Publication Number:
  US 20090000960A1
• Time in Patent Office: 1,336 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
• 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 art enzyme, can be added to facilitate the electrooxidation or etectroreduction 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 arnperometric, voltammetric and potentiometric techniques, can also be used. The invention can be used to determine the concentration of a biomolecute, 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 biomolecute 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:

piercing a portion of the skin of a patient to create a flow of a body fluid;

transporting 500 nl or less of the body fluid into an analyte sensor comprising two pairs of electrodes and a redox mediator, each pair of electrodes comprising a working electrode and a reference or counter electrode, wherein the sensor is configured and arranged for determining the concentration of the analyte from 500 nL or less of body fluid;

holding the sample within the analyte sensor in a non-flow through manner such that the sample is in electrolytic contact with the pairs of electrodes; and

determining by coulomtery the concentration of the analyte in the body fluid from the 500 nl or less of body fluid transported into the analyte sensor.

2. The method of claim 1, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from 200 nL or less of body fluid.

3. The method of claim 1, wherein the analyte sensor comprises a sample chamber that is configured and arranged to hold 200 nL or less of body fluid.

4. The method of claim 1, wherein the analyte sensor comprises a sample chamber that is configured and arranged to hold 100 nL or less of body fluid.

5. The method of claim 1, wherein the analyte sensor is configured and arranged for determining a concentration of the analyte from 100 nL or less of the body fluid.

6. The method of claim 1, wherein piercing a portion of the skin of a patient to create a flow of a body fluid comprises creating a flow of no more than 500 nL of a body fluid from the patient.

7. The method of claim 1, wherein piercing a portion of the skin of a patient to create a flow of a body fluid comprises creating a flow of no more than 200 nL of a body fluid from the patient.

8. The method of claim 1, wherein each pair of electrodes is a facing electrode pair.

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

10. The method of claim 9, wherein the enzyme is immobilized on the working electrodes.

11. The method of claim 1, wherein the redox mediator is non-leachably disposed on the working electrodes.

12. The method of claim 11, wherein the redox mediator is immobilized on the working electrodes.

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

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

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

16. The method of claim 1, wherein transporting a portion of the body fluid into an analyte sensor comprises wicking a portion of the body fluid into the analyte sensor which comprises a sample chamber and a sorbent material disposed in the sample chamber for wicking the portion of the body fluid.

17. The method of claim 1, wherein transporting a portion of 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.

18. The method of claim 1, wherein transporting a portion of 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.

19. The method of claim 1, wherein the analyte sensor comprises a sample chamber that is configured and arranged to hold 500 nL or less of body fluid.

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

21. The method of claim 1, wherein the analyte sensor comprises three pairs of electrodes.

22. The method of claim 21, wherein each of said pairs of electrodes is a facing electrode pair.

23. The method of claim 21, wherein the sensor further includes a non-leachable enzyme on the working electrodes.

24. The method of claim 23, wherein the enzyme is immobilized on the working electrodes.

25. The method of claim 21, wherein the redox mediator is non-leachably disposed on the working electrodes.

26. The method of claim 25, wherein the redox mediator is immobilized on the working electrodes.

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

piercing a portion of the skin of a patient to create a flow of a body fluid;

transporting 500 nl or less of the body fluid into an analyte sensor comprising three pairs of electrodes and a redox mediator, each pair of electrodes comprising a working electrode and a reference or counter electrode, wherein the sensor is configured and arranged for determining the concentration of the analyte from 500 nL or less of body fluid;

holding the sample within the analyte sensor in a non-flow through manner such that the sample is in electrolytic contact with the pairs of electrodes; and

determining by coulometry the concentration of the analyte in the 500 nl or less of body fluid transported into the analyte sensor.

28. The method of claim 27, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from 200 nL or less of body fluid.

29. The method of claim 27, wherein the analyte sensor is configured and arranged for determining a concentration of the analyte from 100 nL or less of the body fluid.

30. The method of claim 27, wherein the analyte sensor comprises a sample chamber that is configured and arranged to hold 500 nL or less of body fluid.

31. The method of claim 27, wherein the analyte sensor comprises a sample chamber that is configured and arranged to hold 200 nL or less of body fluid.

32. The method of claim 27, wherein the analyte sensor comprises a sample chamber that is configured and arranged to hold 100 nL or less of body fluid.

33. The method of claim 27, wherein piercing a portion of the skin of a patient to create a flow of a body fluid comprises creating a flow of no more than 500 nL of a body fluid from the patient.

34. The method of claim 27, wherein piercing a portion of the skin of a patient to create a flow of a body fluid comprises creating a flow of no more than 200 nL of a body fluid from the patient.

35. The method of claim 27, wherein transporting a portion of the body fluid comprises transporting no more than 200 nL of the body fluid into the analyte sensor.

36. The method of claim 27, wherein transporting a portion of the body fluid into an analyte sensor comprises wicking a portion of the body fluid into the analyte sensor which comprises a sample chamber and a sorbent material disposed in the sample chamber for wicking the portion of the body fluid.

37. The method of claim 27, wherein transporting a portion of 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.

38. The method of claim 27, wherein transporting a portion of 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.

39. The method of claim 27, wherein each pair of electrodes is a facing electrode pair.

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

piercing a portion of the skin of a patient to create a flow of a body fluid;

transporting 500 nl or less of the body fluid into an analyte sensor comprising one pair of electrodes and a redox mediator, the pair of electrodes comprising a working electrode and a reference or counter electrode, wherein the sensor is configured and arranged for determining the concentration of the analyte from 500 nL or less of body fluid;

holding the sample within the analyte sensor in a non-flow through manner such that the sample is in electrolytic contact with the pair of electrodes; and

determining by coulometry the concentration of the analyte in the 500 nl or less of body fluid transported into the analyte sensor.

41. The method of claim 40, wherein the analyte sensor is configured and arranged for determining the concentration of the analyte from 200 nL or less of body fluid.

42. The method of claim 40, wherein the analyte sensor is configured and arranged for determining a concentration of the analyte from 100 nL or less of the body fluid.

43. The method of claim 40, wherein the analyte sensor comprises a sample chamber that is configured and arranged to hold 500 nL or less of body fluid.

44. The method of claim 40, wherein the analyte sensor comprises a sample chamber that is configured and arranged to hold 200 nL or less of body fluid.

45. The method of claim 40, wherein the analyte sensor comprises a sample chamber that is configured and arranged to hold 100 nL or less of body fluid.

46. The method of claim 40, wherein piercing a portion of the skin of a patient to create 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 40, wherein piercing a portion of the skin of a patient to create 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 40, wherein transporting a portion of the body fluid comprises transporting no more than 200 nL of the body fluid into the analyte sensor.

49. The method of claim 40, wherein transporting a portion of the body fluid into an analyte sensor comprises wicking a portion of the body fluid into the analyte sensor which comprises a sample chamber and a sorbent material disposed in the sample chamber for wicking the portion of the body fluid.

50. The method of claim 40, wherein transporting a portion of 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.

51. The method of claim 40, wherein transporting a portion of 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.

52. The method of claim 40, wherein the pair of electrodes is a facing electrode pair.

53. The method of claim 40, wherein the analyte sensor comprises glucose oxidase or glucose dehydrogenase.

54. The method of claim 40, wherein the redox mediator comprises an osmium complex, a ferrocyanide, or a ferricyanide.

55. The method of claim 40, wherein the working electrode is constructed of a material selected from gold, carbon, platinum, ruthenium dioxide and palladium.

56. The method of claim 40, wherein the working electrode is separated from the reference or counter electrode by a distance of less than 200 micrometer.

57. The method of claim 40, wherein the piercing comprise piercing the skin on a forearm of the patient.