Methods of determining analyte concentration having enhanced stability and hematocrit performance

• US 9,239,312 B2
• Filed: 04/14/2014
• Issued: 01/19/2016
• 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:
  US14/252,226
• Publication Number:
  US 20140305808A1
• Time in Patent Office: 645 Days
• US Class Current: 1/1
• 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 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.

Claims

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

applying a sample to an electrochemical sensor strip, the sensor strip including a first electrode, the first electrode including at least one first layer on a first conductor, the at least one first layer including an enzyme system and at most 8 μ

g/mm² of a mediator,

wherein the mediator assists in transferring electrons between an analyte in the sample and the first conductor;

applying a pulse sequence to the sample, the pulse sequence comprising at least 2 duty cycles within 3 to 14 seconds, wherein the at least 2 duty cycles each comprise an excitation, and the excitations are separated by a relaxation,

wherein the relaxation provides an output current reduction to one-half or less of the current flow at the excitation maxima;

determining current measurements from the sample responsive to the pulse sequence; and

determining the concentration of the analyte in the sample from the current measurements, the determined concentration having at least one of a stability bias of less than ±

10%, a hematocrit bias of less than ±

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

2. The method of claim 1, wherein the relaxation is from 0.2 to 3 seconds in duration.

3. The method of claim 1, wherein the relaxation is from 0.5 to 1 second in duration.

4. The method of claim 1, wherein the excitations of the at least 2 duty cycles have a duration of at most 2 seconds.

5. The method of claim 1, wherein the excitations of the at least 2 duty cycles have a duration from 0.01 to 3 seconds.

6. The method of claim 1, wherein the excitations of the at least 2 duty cycles have a duration from 0.75 to 3 seconds.

7. The method of claim 1, wherein the excitations have a summed duration of at most 10 seconds.

8. The method of claim 1, wherein the excitations comprise at most 45% of the time of the pulse sequence.

9. The method of claim 1, wherein the excitations of the at least 2 duty cycles are of different amplitudes.

10. The method of claim 9, wherein the different amplitudes are within 500 mV.

11. The method of claim 9, wherein the excitations of the at least 2 duty cycles include one excitation having a greater amplitude than the other excitation.

12. The method of claim 1, the pulse sequence comprising at least 3 duty cycles within 9 seconds.

13. The method of claim 1, the pulse sequence comprising at least 3 duty cycles within 30 seconds.

14. The method of claim 1, wherein the pulse sequence is complete in at most 5 seconds.

15. The method of claim 1, wherein the determining the concentration of the analyte in the sample includes determining the concentration of the analyte in the sample from a current measurement taken within 2 seconds of applying the pulse sequence.

16. The method of claim 1, wherein the pulse sequence includes an initial excitation from 0.75 to 3 seconds in duration, wherein the initial excitation is longer in duration than the excitations of the at least 2 duty cycles.

17. The method of claim 1, wherein the relaxation is responsive to an open circuit.

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

5%.

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

5% after the strip is stored at 50°

C. for 4 weeks when compared to a comparison strip stored at −

20°

C. for 4 weeks.

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

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

21. The method of claim 1, wherein the intercept to slope ratio is at most 10 mg/dL.