Systems and methods for high accuracy analyte measurement

• US 9,632,054 B2
• Filed: 12/31/2010
• Issued: 04/25/2017
• Est. Priority Date: 12/31/2010
• Status: Active Grant

• Current Assignee: Universal Biosensors Pty Ltd. (Universal Biosensors, Inc.)
• Original Assignee: Cilag Gmbh International (Johnson & Johnson)
• Inventors: Chatelier, Ronald C., Hodges, Alastair M.
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US13/824,308
• Publication Number:
  US 20130306493A1
• Time in Patent Office: 2,307 Days
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: C12Q 1/025 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics antimicrobial activity C12Q1/18
• CPC Class Codes: G01N 27/30 Electrodes, e.g. test electrodes; Half-cells G01N27/414 takes precedence
• 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 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 27/413 Concentration cells using liquid electrolytes measuring currents or voltages in voltaic cells
• CPC Class Codes: G01N 27/4163 checking the operation of, or calibrating, the measuring apparatus G01N27/3274, G01N27/4175 and G01N33/0006 take precedence
• 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

Abstract

Methods for determining a concentration of an analyte in a sample, and the devices and systems used in conjunction with the same, are provided herein. In one exemplary embodiment of a method for determining a concentration of an analyte in a sample, a sample including an analyte is provided in a sample analyzing device having a working and a counter electrode. An electric potential is applied between the electrodes and a first analyte concentration is determined. A second analyte concentration value is calculated from the first analyte concentration value and corrected for temperature effects, fill time and capacitance to provide for a final analyte concentration value.

Claims

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

detecting a sample including an analyte introduced to an electrochemical sensor, the electrochemical sensor comprising two electrodes in a spaced apart configuration;

reacting the analyte to cause a physical transformation of the analyte between the two electrodes;

measuring current outputs at discrete intervals to derive a fill time of the sample in the sensor and a capacitance of the electrochemical sensor with the sample;

determining a first analyte concentration value from the current outputs;

calculating a second analyte concentration value from the current outputs and the first analyte concentration value;

correcting the second analyte concentration value for temperature effects to provide for a third analyte concentration value;

correcting the third analyte concentration value as a function of the fill time of the sensor to provide for a fourth analyte concentration value; and

correcting the fourth analyte concentration value as a function of the capacitance to provide for a final analyte concentration value in which the current outputs measured at discrete intervals comprise a first current summation i_r and a second current summation i_l where;

2. The method of claim 1, in which the step of determining the first analyte concentration value includes calculating an analyte concentration G1 with an equation of the form:

3. The method of claim 1, in which the step of calculating the second analyte concentration value includes calculating an analyte concentration G2 with an equation of the form:

4. The method of claim 1, in which the third analyte concentration value comprises a first temperature correction to the second analyte concentration value whenever an ambient temperature is greater than a first temperature threshold and a second temperature correction whenever the ambient temperature is less than or equal to the first temperature threshold.

5. The method of claim 1, in which the step of correcting the third analyte concentration value as a function of the fill time of the electrochemical sensor comprises calculating a fill time correction factor based on the fill time, wherein the fill time correction factor is about zero when the fill time is less than a first fill time threshold;

the fill time correction factor is calculated based on the fill time when the fill time is greater than the first fill time threshold and less than a second fill time threshold; and

the fill time correction factor comprises a constant value when the fill time is greater than the second fill time threshold; and

correcting the fourth analyte concentration value as a function of the capacitance to provide for a final analyte concentration value.

6. The method of claim 5, in which the first fill time threshold is about 0.2 second and the second fill time threshold is about 0.4 second.

7. The method of claim 6, in which the fourth analyte concentration value equals the third analyte concentration value when the third analyte concentration value is less than about 100 mg/dL;

and the fourth analyte concentration value comprises a product of the third analyte concentration value, with an offset to the fill time correction factor when the third analyte concentration value is greater than about 100 mg/dL.

8. The method of claim 1, in which the final analyte concentration value is set to equal to the fourth analyte concentration value when the fourth analyte concentration value is less than a first concentration threshold.

9. The method of claim 1, in which the final analyte concentration value comprises a product of a capacitance correction factor and the fourth analyte concentration value when the fourth analyte concentration value is greater than a first concentration threshold, the capacitance correction factor for the final analyte concentration value being based on a measured capacitance when the capacitance is less than a first capacitance threshold and the capacitance correction factor is set to a maximum value when the capacitance correction factor is greater than a set value.

10. A method of obtaining increased accuracy of a test strip, the method comprising:

providing a batch of test strips with each test strip having a reaction chamber, the reaction chamber including two electrodes spaced apart with a reagent disposed therebetween, and further comprising one or more adhesive layers;

introducing a referential sample containing a referential concentration of an analyte to each of the batch of test strips;

reacting the analyte to cause a physical transformation of the analyte between the two electrodes;

measuring current outputs at discrete intervals to derive a fill time of the referential sample into the test strip and a capacitance of the test strip with the referential sample, the capacitance being a function of a slow flow of the one or more adhesive layers into the reaction chamber based on the age or storage condition of the test strip;

determining a first analyte concentration value from the current outputs;

calculating a second analyte concentration value from the current outputs and the first analyte concentration;

correcting the second analyte concentration value for temperature effects to provide for a third analyte concentration value;

correcting the third analyte concentration value as a function of the fill time of the sensor to provide for a fourth analyte concentration value; and

correcting the fourth analyte concentration value as a function of the capacitance to provide for a final analyte concentration value for each of the batch of test strips, in which the final analyte concentration value is set to equal to the fourth analyte concentration value when the fourth analyte concentration value is less than a first concentration threshold, wherein at least 95% of the final analyte concentration values of the batch of test strips are within 10% of the referential analyte concentration.

11. An analyte measurement device comprising:

a housing;

a strip port connector mounted on the housing and configured to receive an analyte test strip; and

a microprocessor disposed in the housing, the microprocessor being connected to the strip port connector, a power supply and a memory such that when an analyte test strip is coupled to the strip port with a sample deposited in a test chamber of the test strip, the analyte is caused to react between two electrodes and provide for a first analyte concentration estimate G1 based on measured output current values over discrete intervals during a reaction of the analyte, a second analyte concentration estimate G2 based on measured output current values over discrete intervals during a reaction of the analyte, a temperature corrected analyte concentration value G3 from the second analyte concentration value G2, a sample fill time corrected analyte concentration value G4 from the temperature corrected analyte concentration G3, and a test strip capacitance corrected final concentration value G5 from the sample fill-time corrected analyte concentration value G4 in which the discrete intervals comprise a first interval from about 3.9 seconds to about 4 seconds and a second interval from about 4.25 seconds to about 5 seconds, the first and second intervals being measured from the time a sample is deposited in the test chamber, such that the output current values measured over the first and second intervals comprise a first current summation i_r and a second current summation i_l where

12. The device of claim 11, in which the first analyte concentration value G1 comprises derivation of the current values with an equation of the form:

13. The device of claim 12, in which i₂ further comprises an equation of the form:

14. The device of claim 12, in which i_ss comprises an equation of the form:

15. The device of claim 11, in which the second analyte concentration value G2 comprises derivation with an equation of the form:

16. The device of claim 11, in which the temperature corrected analyte concentration value G3 is corrected by a fill time correction factor based on a fill time, the fill time correction factor is about zero when the fill time is less than a first fill time threshold and when the fill time is greater than the first fill time threshold and less than a second fill time threshold, the fill time correction factor is calculated based on the fill time, and when the fill time is greater than the second fill time threshold, the fill time correction factor comprises a constant value.

17. The device of claim 16, in which the first fill time threshold is about 0.2 second and the second fill time threshold is about 0.4 second.

18. The device of claim 16, in which the temperature corrected analyte concentration value G3 is a first temperature correction to the second analyte concentration value G2 whenever an ambient temperature is greater than first temperature threshold and a second temperature correction whenever the ambient temperature is less than or equal to the first temperature threshold.

19. The device of claim 18, in which the sample fill time corrected analyte concentration value G4 is the temperature corrected analyte concentration value G3 when the temperature corrected analyte concentration value G3 is less than about 100 mg/dL and the sample fill time corrected concentration value G4 is a percentage increase in the temperature corrected analyte concentration value in view of the fill time correction factor when the temperature corrected analyte concentration value G3 is greater than about 100 mg/dL.

20. The device of claim 11, in which the test strip capacitance corrected final concentration value G5 is set equal to the sample fill time corrected analyte concentration value when the sample fill-time corrected analyte concentration value G4 is less than a first concentration threshold.

21. The device of claim 11, in which the test strip capacitance corrected final concentration value G5 is a product of a capacitance correction factor and the sample fill time corrected analyte concentration value G4 when the sample fill time corrected analyte concentration value G4 is greater than a first concentration threshold, the capacitance correction factor for the corrected final concentration value G5 being based on a measured capacitance when the capacitance is less than a first capacitance threshold and the capacitance correction factor is set to a maximum value when the capacitance correction factor is greater than a set value.