Small volume in vitro analyte sensor

• US 7,906,009 B2
• Filed: 07/30/2008
• Issued: 03/15/2011
• 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, Say, James, Vreeke, Mark S., Feldman, Benjamin J.
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US12/182,867
• Publication Number:
  US 20090000961A1
• Time in Patent Office: 958 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
• 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, amperometry, voltammetry, and potentiometry. 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 sample from a patient, the method comprising:

(a) piercing the patient with a sample acquisition element of an integrated device comprising a sample acquisition element and an electrochemical sensor to obtain a sample;

(b) transporting no more than 500 nl of the sample into the electrochemical sensor, the sensor comprising;

(i) a spacer layer;

(ii) a first inert base having a first electrode thereon, the first base positioned against the spacer layer with the first electrode proximate the spacer layer;

(iii) a second inert base having a second electrode thereon, the second base positioned against the spacer layer with the second electrode proximate the spacer layer, the first and second electrodes being a facing electrode pair;

(iv) the spacer layer, first base and second base together defining a sample chamber having a volume of no more than about 500 nl;

(v) a redox mediator and an enzyme present in the sample chamber; and

(vi) a tapered tip into which the sample enters, wherein the sample acquisition element faces in the same direction as the tapered tip and is movable in a parallel manner relative to the sensor;

(c) holding the sample in the sample chamber of the electrochemical sensor in a non-flow through manner; and

(d) determining the concentration of analyte in the sample by electrochemistry.

2. The method of claim 1, wherein the

sample chamber comprises a measurement zone having a volume of less than 0.2 microliter.

3. The method of claim 1, wherein the

sample chamber comprises a measurement zone having a volume of less than 0.1 microliter.

4. The method of claim 1, where the

sample acquisition element comprises a lancet.

5. The method of claim 1, where

sample acquisition element comprises a resilient deflectable strip.

6. The method of claim 1, wherein the

redox mediator is selected from the group consisting of osmium complexes, ruthenium complexes, iron complexes, and cobalt complexes.

7. The method of claim 6, wherein the

redox mediator is ferricyanide or ferrocyanide.

8. The method of claim 1, wherein the

redox mediator is a non-leachable redox mediator.

9. The method of claim 1, wherein the step of determining the concentration of analyte in the sample comprises:

(a) determining the concentration of analyte in the sample by coulometry.

10. A method for determining a concentration of an analyte in a sample from a patient, the method comprising:

(a) piercing the patient with a sample acquisition element to obtain the sample, the sample acquisition element being part of an integrated device comprising the sample acquisition element and an analyte sensor, the analyte sensor comprising;

(i) a first inert base and a second inert base;

(ii) a first electrode and a second electrode;

(iii) a sample chamber having a volume of no more than 500 nl for receiving and holding the sample in electrolytic contact with the first electrode and the second electrode, the sample chamber extending to an edge of the sensor and forming an opening therein between the bases;

(iv) a redox mediator and an enzyme present in the sample chamber; and

(v) a proximal end into which the sample enters, wherein the sample acquisition element faces in the same direction as the proximal end of the sensor and is movable in a parallel manner relative to the sensor;

(b) transporting no more than 500 nl of the sample to the sample chamber of the sensor;

(c) holding the sample in the sample chamber of the sensor in a non-flow through manner; and

(d) determining the concentration of analyte in the sample by electrochemistry.

11. The method of claim 10, wherein the

sample chamber comprises a measurement zone having a volume of less than 0.2 microliter.

12. The method of claim 10, wherein the

sample chamber comprises a measurement zone having a volume of less than 0.1 microliter.

13. The method of claim 10, wherein the

sample acquisition element comprises a lancet.

14. The method of claim 10, wherein the

sample acquisition element comprises a resilient deflectable strip.

15. The method of claim 10, wherein the

redox mediator is selected from the group consisting of osmium complexes, ruthenium complexes, iron complexes, and cobalt complexes.

16. The method of claim 15, wherein the

redox mediator is ferricyanide or ferrocyanide.

17. The method of claim 10, wherein the

redox mediator is a non-leachable redox mediator.

18. The method of claim 10, wherein the step of determining the concentration of analyte in the sample comprises:

(a) determining the concentration of analyte in the sample by coulometry.