Small volume in vitro analyte sensor

• US 8,808,531 B2
• Filed: 01/13/2005
• Issued: 08/19/2014
• 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:
  US11/035,131
• Publication Number:
  US 20050164322A1
• Time in Patent Office: 3,505 Days
• Field of Search: 20440301-40315, 205/777.5, 205/778, 205/792
• US Class Current: 205/777.5
• 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 concentration of analyte in a sample having a volume of less than about 1 μL. The sensor has a working electrode coated with a redox mediator that acts as an electron transfer agent between the analyte and the electrode. A second electron transfer agent, such as an enzyme, can be added to facilitate the electrooxidation or electroreduction of the analyte. Various electrochemical detection methods, such as amperometric, voltammetric, and potentiometric techniques, can be used to determine the analyte concentration. The sensor can be used to determine the concentration of a biomolecule, such as glucose or lactate, in a biological fluid, such as blood or serum.

Claims

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

(a) transporting a sample into a sample chamber of a sensor, the sample chamber comprising;

(i) an electrode pair comprising a working electrode disposed on a first substrate and a counter electrode disposed on a second substrate, wherein the working and counter electrodes are in a facing configuration;

(ii) a dielectric layer disposed between the working electrode and the counter electrode;

(iii) a sample chamber bounded in part by side walls of the dielectric layer, the working electrode and the counter electrode and,

(iv) a sensing layer comprising an analyte-responsive enzyme and a redox mediator, wherein the sensing layer is disposed in the sample chamber and on the working electrode and at least a portion of the side walls of the dielectric layer;

(b) generating a sensor signal at the working electrode; and

(c) determining by coulometry the concentration of the analyte using the sensor signal.

2. The method of claim 1, wherein the dielectric layer is disposed on the working electrode, wherein prior to the transporting of the sample, the dielectric material is disposed on working electrode followed by the sensing layer being disposed on the working electrode.

3. The method of claim 1, wherein the sample chamber sized to contain a volume of no more than about 1 μ

L of sample.

4. The method of claim 1, wherein the working electrode and counter electrode are separated by a distance no greater than 1000 μ

m.

5. The method of claim 1, wherein the working electrode and counter electrode are separated by a distance in a range of 200 to 400 μ

m.

6. The method of claim 1, wherein the sample chamber is sized to contain a volume of no more than about 0.5 μ

L of the sample.

7. The method of claim 1, wherein the sample chamber is sized to contain a volume of no more than about 0.2 μ

L of the sample.

8. The method of claim 1, wherein the sample chamber is sized to contain a volume of no more than about 0.1 μ

L of the sample.

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

10. The method of claim 9, wherein the sample chamber sized to contain a volume of no more than about 1 μ

L of sample.

11. The method of claim 9, wherein the sample chamber sized to contain a volume of no more than about 0.5 μ

L of the sample.

12. The method of claim 9, wherein the sample chamber is sized to contain a volume of no more than about 0.2 μ

L of the sample.

13. The method of claim 1, wherein the analyte is glucose and the analyte-responsive enzyme is glucose oxidase.

14. The method of claim 13, wherein the sample chamber sized to contain a volume of no more than about 1 μ

L of sample.

15. The method of claim 13, wherein the sample chamber sized to contain a volume of no more than about 0.5 μ

L of the sample.

16. The method of claim 13, wherein the sample chamber is sized to contain a volume of no more than about 0.2 μ

L of the sample.

17. The method of claim 1, wherein the analyte is glucose and the analyte-responsive enzyme is glucose dehydrogenase.

18. The method of claim 17, wherein the sample chamber sized to contain a volume of no more than about 1 μ

L of sample.

19. The method of claim 17, wherein the sample chamber sized to contain a volume of no more than about 0.5 μ

L of the sample.

20. The method of claim 17, wherein the sample chamber is sized to contain a volume of no more than about 0.2 μ

L of the sample.

21. The method of claim 1, wherein the redox mediator is air-oxidizable.

22. The method of claim 1, wherein said redox mediator comprises an osmium complex.

23. The method of claim 22, wherein the osmium complex comprises osmium complexed with at least one ligand having a nitrogen-containing heterocycle.

24. The method of claim 1, wherein said analyte is glucose and a signal generated by electrolysis of a buffer solution with 10 mM glucose is at least about seven times greater than a signal generated by electrolysis of a buffer solution with no glucose.