Electrochemical analyte sensor

• US 6,484,046 B1
• Filed: 07/10/2000
• Issued: 11/19/2002
• Est. Priority Date: 03/04/1998
• Status: Expired due to Term

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Therasense Incorporated (Abbott Laboratories Incorporated)
• Inventors: Heller, Ephraim, Heller, Adam, Say, James, Gal, Yoram, Aria, Behrad, Plante, Phillip John, Vreeke, Mark S., Tomasco, Michael F.
• Primary Examiner(s): Shaver, Kevin
• Assistant Examiner(s): Natnithithadha, Navin
• Application Number:
  US09/613,604
• Time in Patent Office: 862 Days
• Field of Search: 600/345, 600/309, 600/306, 600/308, 600/346, 600/347, 600/348, 600/352, 600/354, 600/357, 600/358, 600/365, 600/372, 600/382, 600/384, 600/395, 600/396, 600/397, 600/393
• US Class Current: 600/345
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• 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: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

An electrochemical analyte sensor having conductive traces on a substrate is used to determine a level of analyte in in vitro or in vivo analyte-containing fluids. The electrochemical analyte sensor includes a substrate and conductive material disposed on the substrate, the conductive material forming a working electrode. In some sensors, the conductive material is disposed in recessed channels formed in a surface of the sensor. An electron transfer agent and/or catalyst may be provided to facilitate the electrolysis of the analyte or of a second compound whose level depends on the level of the analyte. A potential is formed between the working electrode and a reference electrode or counter/reference electrode and the resulting current is a function of the concentration of the analyte in the fluid.

Claims

1. An electrochemical sensor comprising:

a flexible, planar substrate;

a first conductive material non-leachably disposed on a first surface of the planar substrate to form one or more working electrodes;

one or more contact pads on the first surface and in electrical contact with the one or more working electrodes;

a second conductive material non-leachably disposed on one of the first surface and a second surface of the planar substrate to form a counter electrode, a reference electrode, or a counter-reference electrode;

a contact pad disposed on the one of the first surface and the second surface and in electrical contact with the counter electrode, reference electrode or counter-reference electrode;

an enzyme non-leachably disposed proximate to the working electrode; and

an analyte mass transport limiting layer disposed over at least a portion of the working electrode to limit transport of an analyte to the working electrode;

wherein the sensor comprises a wide portion and a narrow portion, the narrow portion having a length of 2 cm or less and a width of 2 mm or less, and the narrow portion configured and arranged for subcutaneous implantation into the body of an animal for contact with body fluid of the animal.

2. The electrochemical sensor of claim 1, wherein the first conductive material comprises carbon.

3. The electrochemical sensor of claim 1, wherein the first conductive material consists essentially of carbon.

4. The electrochemical sensor of claim 1, wherein the second conductive material comprises Ag/AgCl.

5. The electrochemical sensor of claim 1, wherein the first conductive material and the second conductive material are the same.

6. The electrochemical sensor of claim 1 comprising one working electrode.

7. The electrochemical sensor of claim 1 comprising two or more working electrodes.

8. The electrochemical sensor of claim 1, wherein the substrate has a thickness in the range of 50-500 μ

m.

9. The electrochemical sensor of claim 8, wherein the substrate has a thickness in the range of 100-300 μ

m.

10. The electrochemical sensor of claim 1, wherein the narrow portion has a width in the range of 1 mm or less.

11. The electrochemical sensor of claim 10, wherein the narrow portion has a width in the range of 0.5 mm or less.

12. The electrochemical sensor of claim 1, further comprising an electron transfer agent nonleachably disposed proximate the working electrode to transfer electrons between the working electrode and the analyte.

13. The electrochemical sensor of claim 12, wherein the electron transfer agent is immobilized on the working electrode.

14. The electrochemical sensor of claim 12, wherein the electron transfer agent comprises a redox polymer.

15. The electrochemical sensor of claim 12, wherein at least 90% of the electron transfer agent remains disposed on the working electrode after immersion in interstitial fluid at 37°

C. for 24 hours.

16. The electrochemical sensor of claim 5, wherein at least 99% of the electron transfer agent remains disposed on the working electrode after immersion in interstitial fluid at 37°

C. for 24 hours.

17. The electrochemical sensor of claim 12, wherein at least 90% of the electron transfer agent remains disposed on the working electrode after immersion in interstitial fluid at 37°

C. for 72 hours.

18. The electrochemical sensor of claim 12, wherein the electron transfer agent is immobilized in a sol-gel material.

19. The electrochemical sensor of claim 1, further comprising:

a recessed channel formed in a surface of the substrate; and

a conductive material disposed in the recessed channel and forming the working electrode.

20. The electrochemical sensor of claim 19, wherein the recessed channel has a width of 250 μ

m or less.

21. The electrochemical sensor of claim 19, further comprising a second recessed channel and a second conductive material disposed in the recessed channel, the second conductive material forming a counter electrode.

22. The electrochemical sensor of claim 21, further comprising a third recessed channel and a third conductive material disposed in the channel, the third conductive material forming a reference electrode.

23. The electrochemical sensor of claim 1, further comprising a biocompatible coating disposed over at least a portion of the working electrode.

24. The electrochemical sensor of claim 1, further comprising a temperature probe disposed on the substrate, the temperature probe having a plurality of spaced-apart probe leads and a temperature-dependent element in contact with the spaced-apart probe leads, the temperature-dependent element comprising a material having a temperature-dependent characteristic that produces a change in a signal of the temperature probe in response to a change in temperature.

25. The electrochemical sensor of claim 24, wherein the temperature-dependent characteristic comprises a resistance of the probe element.

26. The electrochemical sensor of claim 24, wherein the material of the temperature-dependent element comprises carbon.

27. The electrochemical sensor of claim 24, wherein the temperature-dependent element comprises a conductive material with a smaller cross-section than the probe leads.

28. The electrochemical sensor of claim 24, wherein the temperature-dependent element is disposed in a recessed channel on a surface of the substrate.

29. The electrochemical sensor of claim 24, wherein the probe leads are disposed in recessed channels on a surface of the substrate.

30. The electrochemical sensor of claim 1, wherein a portion of the electrochemical sensor is configured for implantation into an animal and an anticlotting agent is disposed on a portion of the substrate that is configured for implantation.

31. The electrochemical sensor of claim 1, wherein the mass transport limiting layer is made of a film that absorbs less than 5 wt. % of fluid over a 24 hour period in the temperature range of 250°

C. to 45°

C.

32. The electrochemical sensor of claim 1, wherein the permeability of the mass transport limiting layer to the analyte changes no more that 4% per C in the temperature range of 30°

C. to 40°

C.

33. The electrochemical sensor of claim 1, wherein the mass transport limiting layer includes pores of 3 to 20,000 nm in diameter.

34. The electrochemical sensor of claim 1, wherein at least one of the one or more contact pads comprises a conductive polymer.

35. The electrochemical sensor of claim 1, comprising one or more contact pads disposed on the first surface of the substrate and in electrical contact with the one or more working electrodes, wherein at least one of the one or more contact pads consists essentially of carbon.

36. A method of determining a level of an analyte in a fluid, the method comprising:

contacting the fluid with the electrochemical sensor of claim 1,

generating an electrical signal in the sensor in response to the presence of the analyte; and

determining a level of the analyte from the electrical signal.

37. The method of claim 36, wherein contacting the fluid with an electrochemical sensor comprises implanting a portion of the electrochemical sensor in an animal so that the electrochemical sensor is in contact with a body fluid of the animal.

38. The method of claim 37, wherein implanting a portion of the electrochemical sensor in an animal comprises subcutaneously implanting the electrochemical sensor in the animal so that the electrochemical sensor is in contact with the interstitial fluid of the animal.