Small volume in vitro analyte sensor

• US 8,728,297 B2
• Filed: 04/13/2006
• Issued: 05/20/2014
• Est. Priority Date: 10/08/1998
• Status: Expired due to Fees

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Feldman, Benjamin J., Heller, Adam, Heller, Ephraim, Mao, Fei, Vivolo, Joseph A., Funderburk, Jeffery V., Colman, Fredric C., Krishnan, Rajesh
• Primary Examiner(s): Van, Luan
• Assistant Examiner(s): Kaur, Gurpreet
• Application Number:
  US11/279,694
• Publication Number:
  US 20060169599A1
• Time in Patent Office: 2,959 Days
• Field of Search: 204/403.01, 20440304-40306, 20440309-40311, 205/792, 205/775
• US Class Current: 205/792
• 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 method for determining the concentration of glucose in a biological fluid sample from a subject, comprising the steps of:

providing a sensor comprising a working electrode, a counter electrode and a sample chamber sized to contain no more than about 1 μ

L of sample, wherein the sample chamber comprises a redox mediator and an analyte responsive enzyme disposed on the working electrode, the redox mediator comprising;

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 monodentate ligand that is a monosubstituted pyridine, and wherein at least one of the ligands is a heterocyclic nitrogen-containing bidentate ligand comprising

2. The method of claim 1, wherein determining the concentration of glucose from the electrolyzed sample comprises determining the concentration of glucose from the electrolyzed sample within a clinically acceptable degree of accuracy.

3. The method of claim 2, wherein determining the concentration of glucose from the electrolyzed sample comprises:

determining the concentration of glucose from about 0.5 μ

L or less of sample in the sample chamber.

4. The method of claim 2, wherein:

providing a sensor comprises providing a sensor comprising a sample chamber sized to contain no more than about 0.5 μ

L of sample; and

determining the concentration of glucose comprises determining the concentration of glucose from about 0.5 μ

L or less of sample in the sample chamber.

5. The method of claim 1, further comprising:

obtaining the biological fluid sample from a finger of the subject.

6. The method of claim 1, further comprising:

obtaining the biological fluid sample from a location other than a finger of the subject.

7. The method of claim 6, wherein obtaining the biological fluid sample comprises obtaining the biological fluid sample from a forearm.

8. The method of claim 1, wherein determining the concentration of glucose is effected by amperometry or coulometry.

9. The method of claim 1, wherein said working electrode and said counter electrode are facing each other.

10. The method of claim 1, wherein said working electrode and said counter electrode are side by side.

11. The method of claim 1, wherein said working electrode is spaced no more than 1000 microns from said counter electrode.

12. The method of claim 1, wherein said analyte responsive enzyme is glucose oxidase or glucose dehydrogenase.

13. The method of claim 1, wherein said sensor electrolyzes at least 20% of said sample.

14. The method of claim 1, wherein the transition metal is osmium.

15. The method of claim 1, wherein R₁ is an alkyl.

16. The method of claim 15, wherein R₁ is methyl.

17. The method of claim 1, wherein at least one of the ligands is a unsubstituted pyridine.

18. A system for determining the concentration of glucose in a biological fluid sample, the system comprising:

(a) a sensor comprising a working electrode, a counter electrode, and a sample chamber sized to contain no more than about 1 μ

L of sample, wherein the sample chamber comprises a redox mediator and an analyte responsive enzyme disposed on the working electrode, the redox mediator comprising;

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 monodentate ligand that is a monosubstituted pyridine, and wherein at least one of the ligands is a heterocyclic nitrogen-containing bidentate ligand comprising

19. The system of claim 18, wherein the sensor is adapted to determine the concentration of glucose from about 1 μ

L or less of sample in the sample chamber within a clinically acceptable degree of accuracy.

20. The system of claim 19, wherein the sample chamber is sized to contain no more than about 0.5 μ

L of sample.

21. The system of claim 19, wherein the sensor comprises a tip-fill sample filling arrangement.

22. The system of claim 21, wherein the end tip fill of the sensor is tapered.

23. The system of claim 19, wherein the sensor comprises a side-fill sample filling arrangement.

24. The system of claim 18, wherein said working electrode and said counter electrode are facing each other.

25. The system of claim 18, wherein said working electrode and said counter electrode are side by side.

26. The system of claim 18, wherein said working electrode is spaced no more than 1000 microns from said counter electrode.

27. The system of claim 18, wherein said analyte responsive enzyme is glucose oxidase or glucose dehydrogenase.

28. The system of claim 18, wherein said sensor electrolyzes at least 20% of said sample.

29. The system of claim 18, wherein the transition metal is osmium.

30. The system of claim 18, wherein R₁ is an alkyl.

31. The system of claim 30, wherein R₁ is methyl.

32. The system of claim 18, wherein at least one of the ligands is a unsubstituted pyridine.