Electrochemical test sensor

• US 10,261,044 B2
• Filed: 08/23/2016
• Issued: 04/16/2019
• Est. Priority Date: 09/22/2006
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Inventors: Wu, Huan-Ping, Nelson, Christine D., Spradlin, Hope, Maurer, Eric
• Primary Examiner(s): Leong, Susan D
• Application Number:
  US15/244,212
• Publication Number:
  US 20160356738A1
• Time in Patent Office: 966 Days
• 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. An electrochemical biosensor for determining an analyte concentration in a fluid sample, the biosensor comprising:

a base;

a first electrode on the base including a first conductor and a first reagent layer, the first reagent layer including a mediator having a deposition density of at most 5 μ

g/mm² and an enzyme system having a deposition density of at most 0.5 μ

g/mm²;

a second electrode on the base; and

a lid, the lid and the base assisting in forming an opening to receive the fluid sample,

wherein the biosensor provides a determined concentration value having a stability bias of less than +/−

10% after storage at 50°

C. for 2 weeks when compared to a comparison biosensor stored at −

20°

C. for 2 weeks.

2. The biosensor of claim 1, wherein the second electrode includes a second conductor and a second reagent layer.

3. The biosensor of claim 2, wherein the second reagent layer is different in composition from the first reagent layer.

4. The biosensor of claim 2, wherein the second reagent layer is the same as the first reagent layer.

5. The biosensor of claim 1, wherein the average initial thickness of the first reagent layer is less than 8 μ

m.

6. The biosensor of claim 5, wherein the average initial thickness of the first reagent layer is less than 4 μ

m.

7. The biosensor of claim 1, wherein the first reagent layer comprises at most 1.3 Units of the enzyme system.

8. The biosensor of claim 1, wherein the stability bias is less than +/−

5% after storage at 50°

C. for 2 weeks when compared to the comparison biosensor stored at −

20°

C. for 2 weeks.

9. The biosensor of claim 1, wherein the first reagent layer further includes a polymeric binder selected from the group consisting of poly(ethylene oxide), polyvinyl alcohol, hydroxyethylene cellulose, carboxy methyl cellulose, and combinations thereof.

10. The biosensor of claim 1, 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.

11. An electrochemical biosensor for determining an analyte concentration in a fluid sample, the biosensor comprising:

a base;

a first electrode on the base including a first conductor and a reagent layer, the reagent layer including a mediator having a deposition density of at most 2 μ

g/mm² and an enzyme system having a deposition density of at most 0.5 μ

g/mm²;

a second electrode on the base; and

a lid, the lid and the base assisting in forming an opening to receive the fluid sample,

wherein the biosensor provides a determined concentration value having a stability bias of less than +/−

10% after storage at 50°

C. for 2 weeks when compared to a comparison biosensor stored at −

20°

C. for 2 weeks.

12. An electrochemical biosensor for determining an analyte concentration in a fluid sample, the biosensor comprising:

a base;

a first electrode on the base including a first conductor and a reagent layer, the reagent layer including a mediator having a deposition density of at most 5 μ

g/mm² and an enzyme system having a deposition density of at most 0.5 μ

g/mm²;

a second electrode on the base; and

a lid, the lid and the base assisting in forming an opening to receive the fluid sample,

wherein the biosensor provides a determined concentration value having a hematocrit bias of less than +/−

10% for whole blood samples including from 20 to 60% hematocrit.

13. The biosensor of claim 12, wherein the hematocrit bias is less than +/−

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

14. The biosensor of claim 12, wherein the average initial thickness of the reagent layer is less than 8 μ

m.

15. The biosensor of claim 12, wherein the reagent layer further includes a polymeric binder selected from the group consisting of poly(ethylene oxide), polyvinyl alcohol, hydroxyethylene cellulose, carboxy methyl cellulose, and combinations thereof.

16. The biosensor of claim 12, 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.

17. An electrochemical biosensor for determining an analyte concentration in a fluid sample, the biosensor comprising:

a base;

a first electrode on the base including a first conductor and a reagent layer, the reagent layer including a mediator having a deposition density of at most 2 μ

g/mm² and an enzyme system having a deposition density of at most 0.5 μ

g/mm²;

a second electrode on the base; and

a lid, the lid and the base assisting in forming an opening to receive the fluid sample,

wherein the biosensor provides a determined concentration value having a hematocrit bias of less than +/−

10% for whole blood samples including from 20 to 60% hematocrit.

18. An electrochemical biosensor for determining an analyte concentration in a fluid sample, the biosensor comprising:

a base;

a first electrode on the base having at least one first layer on a first conductor, the first layer including a reagent layer comprising at most 5 μ

g/mm² of a mediator, and an enzyme system at a deposition density of at most 0.5 μ

g/mm²;

a second electrode on the base; and

a lid, the lid and the base assisting in forming an opening to receive the fluid sample,

wherein the biosensor provides a determined concentration value having an intercept to slope ratio of at most 20 mg/dL.

19. The biosensor of claim 18 wherein the intercept to slope ratio is at most 10 mg/dL.

20. The biosensor of claim 19, wherein the intercept to slope ratio is at most 6 mg/dL.

21. The biosensor of claim 20, wherein the intercept to slope ratio is at most 1 mg/dL.

22. The biosensor of claim 18, wherein the average initial thickness of the reagent layer is less than 8 μ

m.

23. The biosensor of claim 18, wherein the reagent layer further includes a polymeric binder selected from the group consisting of poly(ethylene oxide), polyvinyl alcohol, hydroxyethylene cellulose, carboxy methyl cellulose, and combinations thereof.

24. The biosensor of claim 18, 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. An electrochemical biosensor for determining an analyte concentration in a fluid sample, the biosensor comprising:

a base;

a first electrode on the base having at least one first layer on a first conductor, the first layer including a reagent layer comprising at most 2 μ

g/mm² of a mediator, and an enzyme system at a deposition density of at most 0.8 μ

g/mm²;

a second electrode on the base; and

a lid, the lid and the base assisting in forming an opening to receive the fluid sample,

wherein the biosensor provides a determined concentration value having an intercept to slope ratio of at most 20 mg/dL.

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

applying the fluid sample to an electrochemical biosensor, the biosensor including a base, a first electrode, a second electrode and a lid, the first electrode on the base including a first conductor and a reagent layer, the reagent layer including a mediator having a deposition density of at most 8 μ

g/mm² and an enzyme system having a deposition density of at most 0.8 μ

g/mm², the second electrode on the base, the lid and the base assisting in forming an opening to receive the fluid sample;

applying a pulse sequence to the sample;

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.

27. An electrochemical biosensor for determining an analyte concentration in a fluid sample, the biosensor comprising:

a base;

a first electrode on the base including a first conductor and a reagent layer, the reagent layer including a reagent layer comprising from 1.72 to 2 μ

g/mm² of a mediator and an enzyme system having a deposition density from 0.42 to 0.8 μ

g/mm²;

a second electrode; and

a lid, the lid and the base assisting in forming an opening to receive the fluid sample.

28. An electrochemical biosensor for determining an analyte concentration in a fluid sample, the biosensor comprising:

a base;

a first electrode on the base including a first conductor and a reagent layer, the reagent layer including a reagent layer comprising from 1.72 to 8 μ

g/mm² of a mediator and an enzyme system having a deposition density from 0.42 to 0.8 μ

g/mm²;

a second electrode; and

a lid, the lid and the base assisting in forming an opening to receive the fluid sample.