Biosensor performance increasing methods having enhanced stability and hematocrit performance

• US 8,728,299 B2
• Filed: 11/14/2013
• Issued: 05/20/2014
• Est. Priority Date: 09/22/2006
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Wu, Huan-Ping, Nelson, Christine D., Spradlin, Hope, Maurer, Eric
• Primary Examiner(s): DIETERLE, JENNIFER M
• Application Number:
  US14/079,922
• Publication Number:
  US 20140061062A1
• Time in Patent Office: 187 Days
• Field of Search: 20440301-40315, 205/775, 205/777.5, 205/778, 205/792, 422/82.01, 422/68.1, 435/287.1, 435/817, 435/4
• US Class Current: 205/792
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• 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 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

The present invention relates to electrochemical sensor strips and methods of determining the concentration of an analyte in a sample or improving the performance of a concentration determination. The electrochemical sensor strips may include at most 8 μg/mm² of a mediator. The strips, the strip reagent layer, or the methods may provide for the determination of a concentration value having at least one of a stability bias of less than ±10% after storage at 50° C. for 4 weeks when compared to a comparison strip stored at −20° C. for 4 weeks, a hematocrit bias of less than ±10% for whole blood samples including from 20 to 60% hematocrit, and an intercept to slope ratio of at most 20 mg/dL. A method of increasing the performance of a quantitative analyte determination also is provided.

Claims

1. A method of increasing the performance of a quantitative analyte determination assay comprising:

introducing an analyte containing sample having a liquid component to an electrochemical sensor strip, the strip having a base, a first conductor on the base, a second conductor on the base, and at least one first layer on at least the first conductor,

wherein the at least one first layer includes a reagent layer including a polymeric binder, an enzyme system, and at most 8 μ

g/mm² of a mediator,

wherein the mediator assists in transferring electrons between the analyte containing sample and the first conductor, and

wherein the sample provides electrical communication between the first and the second conductors;

applying an electric potential between the first and the second conductors in the form of at least 2 read pulses within 3 to 14 seconds; and

measuring a current from at least one of the read pulses to provide a quantitative value of the analyte concentration in the sample with increased performance attributable to at least one performance parameter selected from the group consisting of a stability bias of less than ±

10% after the strip is stored at 50°

C. for 2 weeks, a hematocrit bias of less than ±

10% over a 20 to 60% hematocrit range for whole blood samples, an intercept to slope ratio of at most 10 mg/dL, and combinations thereof.

2. The method of claim 1, wherein the at least 2 read pulses are applied within 9 seconds.

3. The method of claim 1, wherein the at least 2 read pulses are complete in at most 5 seconds of applying the electric potential.

4. The method of claim 1, wherein the current measured from at least one of the at least 2 read pulses is measured within 2 seconds of applying the electric potential to provide the quantitative value of the analyte concentration in the sample.

5. The method of claim 1, wherein the at least 2 read pulses are separated by a relaxation providing an output current reduction to one-half or less of current flow at an excitation maxima.

6. The method of claim 1, wherein the at least 2 read pulses have a duration of at most 2 seconds.

7. The method of claim 1, wherein the at least 2 read pulses are of different amplitudes.

8. The method of claim 7, wherein the different amplitudes are within 500 mV.

9. The method of claim 7, wherein the at least 2 read pulses include one read pulse having a greater amplitude than the other read pulse.

10. The method of claim 1, wherein the first and the second conductors are in the same plane.

11. The method of claim 1, further comprising the first layer on the second conductor.

12. The method of claim 1, wherein the first conductor and the second conductor are separated by greater than 200 μ

m.

13. The method of claim 1, further comprising a lid on the base, wherein the first conductor and the second conductor are separated from an upper portion of the lid by at least 100 μ

m.

14. The method of claim 1, wherein the average initial thickness of the reagent layer is less than 8 μ

m.

15. The method of claim 1, wherein the average initial thickness of the reagent layer is from 0.25 to 3 μ

m.

16. The method of claim 1, wherein the reagent layer is formed at a deposition density of at most 0.2 μ

L/mm² from a reagent solution.

17. The method of claim 1, wherein the polymeric binder is selected from the group consisting of poly(ethylene oxide), polyvinyl alcohol, hydroxyethyl cellulose, carboxymethyl cellulose, and combinations thereof.

18. The method of claim 1, wherein the deposition density of the polymeric binder is at most 2 μ

g/mm² on the first conductor.

19. The method of claim 1, wherein the polymeric binder is partially water soluble and forms a gel-like material on hydration.

20. The method of claim 1, wherein the reagent layer comprises the enzyme system at a deposition density of at most 0.8 μ

g/mm².

21. The method of claim 1, wherein the reagent layer comprises at most 1.3 Units of the enzyme system.

22. The method of claim 1, wherein the reagent layer comprises at most 2 μ

g/mm² of the mediator.

23. The strip of claim 1, wherein the mediator is a two electron transfer mediator.

24. The method of claim 23, wherein the mediator is selected from the group consisting of 3-phenylimino-3H-phenothiazines, 3-phenylimino-3H-phenoxazines, salts thereof, acids thereof, derivatives thereof, and combinations thereof.

25. The method of claim 1, wherein the mediator has a redox potential at least 100 mV lower than ferricyanide.

26. The method of claim 1, wherein the stability bias is less than ±

5%.

27. The method of claim 1, wherein the stability bias is less than ±

5% after the strip is stored at 50°

C. for 4 weeks.

28. The method of claim 1, wherein the hematocrit bias is less than ±

5% for whole blood samples including from 20% to 60% hematocrit.

29. The method of claim 1, wherein the intercept to slope ratio is at most 1 mg/dL.

30. The method of claim 1, wherein 45% or less of the total assay time is spent oxidizing the sample with the electric potential.