Concentration determination in a diffusion barrier layer

• US 8,852,422 B2
• Filed: 11/06/2012
• Issued: 10/07/2014
• Est. Priority Date: 10/12/2004
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Wu, Huan-Ping
• Primary Examiner(s): Noguerola, Alex
• Application Number:
  US13/669,674
• Publication Number:
  US 20130098778A1
• Time in Patent Office: 700 Days
• Field of Search: 204/400, 20440301-40315, 205/777.5, 205/778, 205/792, 205/775
• US Class Current: 205/792
• CPC Class Codes: B32B 2307/202 Conductive
• CPC Class Codes: B32B 38/18 Handling of layers or the laminate
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• 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
• CPC Class Codes: G01N 27/3276 being a hybridisation with immobilised receptors using a FET type sensor G01N27/4145; concerning the hybridisation C12Q1/68
• CPC Class Codes: G01N 27/3277 being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48
• CPC Class Codes: G01N 27/40 Semi-permeable membranes or partitions
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

The present invention relates to improved electrochemical biosensor strips and methods for determining the concentration of an analyte in a sample. By selectively measuring a measurable species residing in a diffusion barrier layer, to the substantial exclusion of the measurable species residing exterior to the diffusion barrier layer, measurement errors introduced by sample constituents, such as red blood cells, and manufacturing variances may be reduced.

Claims

1. An electrochemical sensor strip, comprising:

a base;

a first electrode on the base, the first electrode having at least one first layer on a first conductor, the first layer including a reagent layer and a second layer between the first conductor and the first layer, the second layer having an average initial thickness of at least 1 μ

m and the second layer comprising a partially water soluble polymeric material; and

a second electrode on the base.

2. The electrochemical sensor strip of claim 1, where the average initial thickness of the second layer is from 5 to 25 μ

m.

3. The electrochemical sensor strip of claim 2, where the second layer does not include a substantial amount of at least one of the oxidoreductase enzyme and a mediator.

4. The electrochemical sensor strip of claim 3, where the second layer comprises a polymeric material.

5. The electrochemical sensor strip of claim 1, where the second layer does not include a substantial amount of at least one of the oxidoreductase enzyme and a mediator.

6. The electrochemical sensor strip of claim 1, where the polymeric material comprises at least one of poly(ethylene oxide), carboxy methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, derivatives thereof, and combinations thereof.

7. A method of increasing the accuracy of quantitative analyte determination comprising:

receiving an analyte-containing sample in an electrochemical sensor, the analyte-containing sample having a liquid component,

the sensor having a first conductor, a second conductor, and a first layer on at least the first conductor,

where the first layer includes a reagent layer including a binder and a mediator, and the sample provides electrical communication between the first and the second conductors;

applying an electric potential between a first conductor and the second conductor in the form of a read pulse,

the read pulse applied for a duration at which a measurable species within the first layer is substantially detected and the measurable species external to the first layer is not substantially detected; and

determining a quantitative value of the analyte concentration in the sample in response to the read pulse,

where the sample resides in a gap formed between the base and a lid of the sensor, the gap having a volume of at least 1 mL to at most 10 mL.

8. The method of claim 7, further comprising applying an initial pulse and a time delay before the read pulse.

9. The method of claim 8, where the initial pulse is from 1 to 4 seconds.

10. The method of claim 8, where the time delay is from 2 to 4 seconds.

11. A method of increasing the accuracy of quantitative analyte determination comprising:

receiving an analyte-containing sample in an electrochemical sensor, the analyte-containing sample having a liquid component,

the sensor having a first conductor, a second conductor, and a first layer on at least the first conductor,

where the first layer includes a reagent layer including a binder and a mediator, and the sample provides electrical communication between the first and the second conductors;

applying an electric potential between a first conductor and the second conductor in the form of a read pulse,

the read pulse applied for a duration at which a measurable species within the first layer is substantially detected and the measurable species external to the first layer is not substantially detected; and

determining a quantitative value of the analyte concentration in the sample in response to the read pulse,

further comprising applying an initial pulse and a time delay before the read pulse, where the initial pulse is from 1 to 4 seconds.

12. The method of claim 11, where the time delay is from 2 to 4 seconds.

13. An electrochemical system, for determining the concentration of an analyte in a sample, comprising:

a first sensor, the first sensor including;

a base,

a first electrode on the base, the first electrode having at least one first layer on a first conductor, the first conductor on the base, where the first layer includes at least one binder forming a diffusion barrier layer, and

a second electrode; and

a measurement device in electrical communication with the first electrode through the first conductor and in electrical communication with the second electrode through a second conductor;

where the measurement device is capable of applying a read pulse to the first sensor and of determining a quantitative value of the analyte concentration in the sample in response to the read pulse; and

a bias of the quantitative value of the analyte concentration in the sample determined with the first sensor is less than a bias of a quantitative value of the analyte concentration in the sample when determined by the measurement device with the read pulse when in electrical communication with a second sensor,

where the second sensor is identical to the first sensor, but lacks the binder forming the diffusion barrier layer.

14. The electrochemical system of claim 13, where the bias of the quantitative value of the analyte concentration in the sample determined with the first sensor is from about 12% to about 80% less than the bias of the quantitative value of the analyte

concentration in the sample when determined by the measurement device using the read pulse when in electrical communication with the second sensor.

15. The electrochemical system of claim 13, where, when the read pulse is about 0.9 seconds, the bias of the quantitative value of the analyte concentration in the sample determined with the first sensor is from about 37% to about 80% less than the bias of the quantitative value of the analyte concentration in the sample when determined by the measurement device in electrical communication with the second sensor.

16. The electrochemical system of claim 13, where, when the read pulse is about 5 seconds,

the bias of the quantitative value of the analyte concentration in the sample determined with the first sensor is from about 25% to about 60% less than the bias of the quantitative value of the analyte concentration in the sample when determined by the measurement device in electrical communication with the second sensor.

17. The electrochemical system of claim 13, where, when the read pulse is about 10 seconds,

the bias of the quantitative value of the analyte concentration in the sample determined with the first sensor is from about 25% to about 50% less than the bias of the quantitative value of the analyte concentration in the sample when determined by the measurement device in electrical communication with the second sensor.

18. The electrochemical system of claim 13, where, when the read pulse is about 15 seconds,

the bias of the quantitative value of the analyte concentration in the sample determined with the first sensor is from about 12% to about 40% less than the bias of the quantitative value of the analyte concentration in the sample when determined by the measurement device in electrical communication with the second sensor.

19. An electrochemical system, for determining the concentration of an analyte in a sample, comprising:

a first sensor, the first sensor including;

a base,

a first electrode on the base, the first electrode having at least one first layer on a first conductor, the first conductor on the base, where the first layer includes at least one binder forming a diffusion barrier layer, and

a second electrode; and

a measurement device in electrical communication with the first electrode through the first conductor and in electrical communication with the second electrode through a second conductor;

where the measurement device is capable of applying a read pulse of from 1 to 10 seconds to the first sensor and of determining a quantitative value of the analyte concentration in the sample in response to the read pulse; and

the accuracy of the determined quantitative value of the analyte concentration in the sample is higher when a read pulse of 1 second is applied than when a read pulse of 10 seconds is applied.

20. The electrochemical system of claim 19, where the thickness of the diffusion barrier layer is such that the bias of the quantitative value of the analyte concentration in the sample determined with a 1 second read pulse is about 50% less on average than the bias of the quantitative value of the analyte concentration in the sample when determined with a 10 second read pulse.

21. The electrochemical system of claim 19, where the thickness of the diffusion barrier layer is such that the slope of a correlation of measured current from whole blood samples with measured current from plasma samples increases from 0.71 to 0.78 to 0.86 for read pulse durations of 10 seconds, 5 seconds and 1 second, respectively.

22. An electrochemical system, for determining the concentration of an analyte in a sample, comprising:

a first plurality of sensors, each sensor of the first plurality of sensors including;

a base,

a first electrode on the base, the first electrode having at least one first layer on a first conductor, the first conductor on the base, where the first layer includes at least one binder forming a diffusion barrier layer, and

a second electrode; and

a measurement device;

where, when each sensor of the first plurality of sensors is placed in electrical communication with the measurement device and an analyte-containing sample is applied to the sensor, the measurement device is capable of applying a read pulse to the sensor and determining a quantitative value of the analyte concentration in the sample in response to the read pulse, and

a bias spread for the quantitative values of the analyte concentration determined from the sample by the measurement device in electrical communication with the first plurality of sensors with the read pulse for a plurality of samples having hematocrit concentrations spanning the range from 16% to 48% is less than a bias spread for the plurality of samples when determined by the measurement device in electrical communication with a second plurality of sensors with the read pulse,

where the second plurality of sensors is identical to the first plurality of sensors, but lacks the binder forming the diffusion barrier layer.