Determining analyte concentration from variant concentration distribution in measurable species

• US 10,190,150 B2
• Filed: 03/10/2015
• Issued: 01/29/2019
• Est. Priority Date: 10/24/2006
• 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, Charlton, Steven C., Chu, Amy H., Edelbrock, Andrew J., Jung, Sung-Kwon, Huang, Dijia
• Primary Examiner(s): Fritchman, Rebecca M
• Application Number:
  US14/643,134
• Publication Number:
  US 20150176054A1
• Time in Patent Office: 1,421 Days
• Field of Search: 435 14
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52

Abstract

A biosensor system determines an analyte concentration of a biological sample using an electrochemical process without Cottrell decay. The biosensor system generates an output signal having a transient decay, where the output signal is not inversely proportional to the square root of the time. The transient decay is greater or less than the −0.5 decay constant of a Cottrell decay. The transient decay may result from a relatively short incubation period, relatively small sample reservoir volumes, relatively small distances between electrode surfaces and the lid of the sensor strip, and/or relatively short excitations in relation to the average initial thickness of the reagent layer. The biosensor system determines the analyte concentration from the output signal having a transient decay.

Claims

1. An electrochemical method for determining an analyte concentration in a sample, comprising:

receiving a sample including a biological fluid at a sample reservoir, the sample reservoir having a reagent layer including an enzyme disposed in the sample reservoir and a pair of electrodes partially or completely disposed in the sample reservoir such that the sample contacts both the enzyme and the pair of electrodes responsive to being received at the sample reservoir, the contact between the sample and the enzyme causing a reaction between the enzyme and an analyte in the sample such that the analyte begins to undergo a redox conversion to electrochemically form a measurable species from the reaction between the enzyme and the analyte, the electrochemical forming of the measurable species resulting from a transfer of electrons from or to the analyte during the redox conversion of the analyte;

applying, by a signal generator, an electrical input signal having an excitation and a relaxation to the sample via the pair of electrodes after an incubation period, the incubation period being less than a reference period, wherein at the end of the reference period (i) all of the analyte has undergone the redox conversion to the measureable species and (ii) the measurable species has a constant concentration distribution, and wherein at the end of the incubation period (i) a portion but not all of the analyte has undergone the redox conversion to the measurable species and (ii) the measurable species has a variant concentration distribution, the reference period being based on a height of the sample reservoir, a volume of the sample reservoir, a thickness of the reagent layer, or any combination thereof, the incubation period beginning when the sample is received at the reservoir, the applying of the electrical input signal producing an electrical output signal that is based on the analyte concentration of the sample;

measuring, by a processor, the electrical output signal; and

determining, by the processor, the analyte concentration of the sample as a function that includes the measured electrical output signal.

2. The method of claim 1, wherein the variant concentration distribution represents an incomplete redox conversion of the analyte to the measurable species.

3. The method of claim 1, wherein the variant concentration distribution undergoes a substantial change from a surface of at least one of the pair of electrodes to an upper lid of the sample reservoir that is filled with the sample.

4. The method of claim 3, wherein the height of the sample reservoir is from 100 to 250 μ

m.

5. The method of claim 1, wherein the variant concentration distribution represents the measurable species undergoing a transient condition.

6. The method of claim 5, wherein the transient condition manifests as a transient decay of the output signal.

7. The method of claim 6, wherein the transient decay has a decay constant less than −

0.5 or greater than −

0.5.

8. The method of claim 7, wherein the transient decay is a non-Cottrell decay.

9. The method of claim 7, wherein the decay constant is from 0.52 to 1 or at most −

0.35.

10. The method of claim 1, wherein the analyte concentration is determined before the analyte undergoes complete conversion to the measurable species.

11. The method of claim 1, wherein the electrical input signal includes a plurality of excitations and a plurality of relaxations.

12. The method of claim 11, wherein at least one of the excitations has a duration from 0.1 to 5 seconds or from 0.1 to 1 second.

13. The method of claim 11, wherein at least one of the relaxations has a duration from 0.1 to 3 seconds.

14. The method of claim 1, wherein the electrical input signal is a voltage and the output signal is a current.

15. The method of claim 1, wherein the incubation period does not exceed 4 seconds.

16. The method of claim 1, wherein the incubation period does not exceed 1 second.

17. The method of claim 1, wherein the incubation period does not exceed 0.1 seconds.

20. The method of claim 1, wherein the output signal is produced from the excitation of the electrical input signal.

18. An electrochemical method for determining an analyte concentration in a sample, comprising:

receiving a sample including a biological fluid at a sample reservoir, the sample reservoir having a reagent layer including an enzyme disposed in the sample reservoir and a pair of electrodes partially or completely disposed in the sample reservoir such that the sample contacts both the enzyme and the pair of electrodes responsive to being received at the sample reservoir, the contact between the sample and the enzyme causing a reaction between the enzyme and an analyte in the sample such that the analyte begins to undergo a redox conversion to electrochemically form a measurable species from the reaction between the enzyme and the analyte, the electrochemical forming of the measurable species resulting from a transfer of electrons from or to the analyte during the redox conversion of the analyte;

applying, by a signal generator, an electrical input signal having an excitation and a relaxation to the sample via the pair of electrodes after an incubation period, the incubation period being less than a reference period, wherein at the end of the reference period (i) all of the analyte has undergone the redox conversion to the measureable species and (ii) the measurable species has a constant concentration distribution, and wherein at the end of the incubation period (i) a portion but not all of the analyte has undergone the redox conversion to the measurable species and (ii) the measurable species has a variant concentration distribution, the reference period being based on a height of the sample reservoir, a volume of the sample reservoir, a thickness of the reagent layer, or any combination thereof, the incubation period beginning when the sample is received at the reservoir, the applying of the electrical input signal producing an electrical output signal that is based at least partially on the analyte concentration of the sample and has a non-Cottrell transient decay;

measuring, by a processor, the electrical output signal; and

determining, by the processor, the analyte concentration of the sample as a function that includes the measured electrical output signal.

19. A method for determining an analyte concentration in a sample, comprising:

receiving a sample including a biological fluid at a sample reservoir, the sample reservoir having a reagent layer including an enzyme disposed in the sample reservoir and a pair of electrodes partially or completely disposed in the sample reservoir such that the sample contacts both the enzyme and the pair of electrodes responsive to being received at the sample reservoir, the contact between the sample and the enzyme causing a reaction between the enzyme and an analyte in the sample such that the analyte begins to undergo a redox conversion to electrochemically form a measurable species from the reaction between the enzyme and the analyte, the electrochemical forming of the measurable species resulting from a transfer of electrons from or to the analyte during the redox conversion of the analyte;

applying, by a signal generator, an electrical input signal having an excitation and a relaxation to the sample via the pair of electrodes after an incubation period, the incubation period being less than a reference period, wherein at the end of the reference period (i) all of the analyte has undergone the redox conversion to the measureable species and (ii) the measurable species has a constant concentration distribution, and wherein at the end of the incubation period (i) a portion but not all of the analyte has undergone the redox conversion to the measurable species and (ii) the measurable species has a variant concentration distribution, the reference period being based on a height of the sample reservoir, a volume of the sample reservoir, a thickness of the reagent layer, or any combination thereof, the incubation period beginning when the sample is received at the reservoir, the applying of the electrical input signal producing an electrical output signal that is based at least partially on the analyte concentration of the sample and has a decay constant less than −

0.5 or greater than −

0.5;

measuring, by a processor, the electrical output signal; and

determining, by the processor, the analyte concentration of the sample as a function that includes the measured electrical output signal.