System and method for determination of a concentration of at least one interfering substance and correction of glucose concentration based on the concentration of the interfering substance

• US 9,244,036 B2
• Filed: 11/16/2012
• Issued: 01/26/2016
• Est. Priority Date: 11/16/2012
• Status: Active Grant

• Current Assignee: LifeScan IP Holdings, LLC
• Original Assignee: Cilag Gmbh International (Johnson & Johnson)
• Inventors: Colas, Aurelie
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US13/679,906
• Publication Number:
  US 20140138261A1
• Time in Patent Office: 1,166 Days
• US Class Current: 1/1
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771

Abstract

Described are methods and systems to apply a plurality of test voltages to the test strip and measure a current transient output resulting from an electrochemical reaction in a test chamber of the test strip so that an estimated interferent value can be determined so that such interferent value can be used to correct the current transients at specific time points for more accurate glucose concentration determination.

Claims

1. A method of determining an interferent corrected glucose concentration from a fluid sample with a glucose monitor and a biosensor, the method comprising the steps of:

ascertaining historical data relating to at least one interferent in physiological fluid samples by;

determining a historical mean concentration for the at least one interferent including various standards of deviations from a plurality of physiological fluid samples measured separately by a referential interferent sensor at various glucose concentrations;

storing the historical mean concentration of the at least one interferent in the plurality of physiological fluid samples;

measuring a current output transient of each of the plurality of the physiological fluid samples with respect to time points during a test sequence; and

obtaining historical regression of slopes and intercepts, along with coefficients of determination of the current output transient at corresponding time points with respect to the test interval for each sample of the plurality of samples; and

retaining as historical data for each time point of the current transient of each of the physiological samples, the following parameters from regression analyses as a function of the at least one interferent concentration at each specific glucose concentration;

(a) regression slope, (b) regression intercept, and (c) coefficient of determination associated with the regression slope and regression intercept;

depositing a physiological fluid sample in a test chamber of the biosensor to start a test sequence;

applying a plurality of potentials to electrodes disposed in the test chamber of the biosensor over a time interval of the test sequence;

measuring a current output transient over a plurality of time points during the time interval of the test sequence to provide a measured current output transient for each of the plurality of time points;

estimating a glucose concentration of a fluid sample from the measured current output transient of the measuring step;

categorizing the estimated glucose concentration into one of plural distinct categories of glucose magnitudes;

estimating a plurality of the at least one interferent concentrations at specific time points based on;

(a) the measured current output transient; and

(b) historical slopes and historical intercepts of current transient output for historical interferent concentrations that have been collected in the one category of glucose magnitudes;

determining an estimated mean interferent concentration from the plurality of estimated interferent concentrations from the estimating step;

correcting the measured current output transient based on;

(a) the measured current output transient at the specific time points during the test sequence, (b) the historical slope at the specific time points during the test sequence from historical data, and (c) historical mean interferent concentration and (d) estimated mean interferent concentration of the estimating step; and

calculating a glucose concentration corrected for the presence of at least one interferent based on the measured current output transient that includes the corrected current output transient at the specific time points from the correcting step.

8. The method of one of claim 1, 3, or 7, in which the estimating of the glucose concentration is obtained with an equation of the form:

9. The method of one of claims 1 and 2, in which the calculating of the glucose concentration is performed after completion of the determining step for all of the plurality of time points during the time interval and is performed with an equation of the form:

13. The method of one of claim 1, 2, 7, or 12, in which the at least one interferent or the interfering substance comprises uric acid.

2. A method of determining glucose concentration corrected for presence of interferent from a fluid sample with a glucose monitor and a biosensor, the method comprising the steps of:

depositing a physiological fluid sample in a test chamber of the biosensor to start a test sequence;

applying a plurality of potentials to electrodes disposed in the test chamber of the biosensor over a time interval of the test sequence;

measuring a current output transient over a plurality of time points during the time interval of the test sequence to provide a measured current output transient for each of the plurality of time points;

estimating a glucose concentration of a fluid sample from the measured current output transient of the measuring step;

categorizing the estimated glucose concentration into one of plural distinct categories of glucose magnitudes;

estimating a plurality of at least one interferent concentrations at specific time points based on;

(a) the measured current output transient; and

(b) historical slopes and historical intercepts of current transient output for historical interferent concentrations that have been collected in the one category of glucose magnitudes;

determining an estimated mean of the at least one interferent concentration from the plurality of estimated interferent concentrations from the estimating step;

correcting the measured current output transient based on;

(a) the measured current output transient at the specific time points during the test sequence, (b) the historical slope at the specific time points during the test sequence from historical data, and (c) a historical mean interferent concentration from historical data and (d) estimated mean interferent concentration of the estimating step; and

calculating a glucose concentration corrected for the presence of the at least one interferent based on the measured current output transient that includes the corrected current output transient at the specific time points from the correcting step.

3. The method of claim 2, further comprising:

ascertaining historical data relating to the at least one interferent in physiological fluid samples by;

determining a mean concentration for the at least one interferent from a plurality of physiological fluid samples measured separately by a referential interferent sensor at various glucose concentrations;

storing the mean concentration of at least one interferent in the plurality of physiological fluid samples; and

obtaining historical regression of slopes and intercepts, along with coefficients of determination of current output transient at corresponding time points with respect to a test interval for each sample of the plurality of samples; and

retaining as historical data for each time point of the current transient of each of the physiological samples, the following parameters from regression analyses as a function of the at least one interferent concentration at each specific glucose concentration;

(a) a regression slope, (b) a regression intercept, and (c) a coefficient of determination associated with the regression slope and regression intercept.

4. The method of claim 3, in which the correcting step comprises:

capping or limiting the estimated interferent concentration so that the estimated mean interferent concentration is within ±

3 standard deviations of historical mean concentration of the at least one interferent concentrations;

evaluating whether a historical coefficient of determination from the obtaining step at each of the plurality of time points that have been collected in a test sequence, for the one category of glucose magnitudes, is greater than a predetermined threshold;

if the evaluating step is true, applying a correction to the current output transient for each of the plurality of time points that has a historical coefficient of determination greater than the predetermined threshold;

or

if the evaluating step is false then selecting another time point and returning to the evaluating step.

5. The method of claim 4, in which the estimating of the at least one interferent is performed with an equation of the form:

6. The method of claim 5, further comprising estimating an average interferent concentration based on all of the estimated interferent concentrations at selected time points “

t”

in which the correlation to the interferent and transient are the highest.

7. A method of determining an interferent concentration from a fluid sample with a glucose monitor and a biosensor, the method comprising the steps of:

depositing a physiological fluid sample in a test chamber of the biosensor to start a test sequence;

applying a plurality of potentials to electrodes disposed in the test chamber of the biosensor over a time interval of the test sequence;

measuring a current output transient over a plurality of time points during the time interval of the test sequence to provide a measured current output transient for each of the plurality of time points;

estimating a glucose concentration of a fluid sample from the measured current output transient of the measuring step;

categorizing the estimated glucose concentration into one of plural distinct categories of glucose magnitudes;

estimating a plurality of interferent concentrations at specific time points based on;

(a) the measured current output transient; and

(b) historical slopes and historical intercepts of current transient output for historical interferent concentrations that have been collected in the one category of glucose magnitudes;

determining an estimated mean interferent concentration from the plurality of estimated interferent concentrations from the estimating step; and

annunciating the estimated mean interferent concentration in the sample.

10. An analyte measurement system comprising:

a test strip including;

a substrate;

a plurality of electrodes disposed on the substrate and connected to respective electrode connectors; and

an analyte meter including;

a housing;

a test strip port connector configured to connect to the respective electrode connectors of the test strip; and

a microprocessor in electrical communication with the test strip port connector to apply electrical signals or sense electrical signals from the plurality of electrodes during a test sequence, the microprocessor is configured to;

(a) apply a plurality of potential to electrodes disposed in the test chamber of the biosensor over a time interval of the test sequence;

(b) measure a current output transient over a plurality of time points during the time interval of the test sequence to provide a measured current output transient for each of the plurality of time points;

(c) estimate a glucose concentration of a fluid sample from the measured current output transient of the measuring step;

(d) categorize the estimated glucose concentration into one of plural distinct categories of glucose magnitudes;

(e) estimate a plurality of interferent concentrations at specific time points based on;

(i) the measured current output transient; and

(ii) historical slopes and historical intercepts of current transient output for historical interferent concentrations that have been collected in the one category of glucose magnitudes;

(f) determine an estimated mean interferent concentration from the plurality of estimated interferent concentrations;

(g) correct the measured current output transient based on;

(i) the measured current output transient at the specific time points during the test sequence, (ii) the historical slope at the specific time points during the test sequence from historical data, and (iii) a historical mean interferent concentration from historical data and (iv) estimated mean interferent concentration; and

(h) calculate a glucose concentration corrected for the presence of interferent based on the measured current output transient that includes the corrected current output transient at the specific time points.

11. The system of claim 10, in which the interferent comprises uric acid.

12. A method of determining glucose concentration corrected for effects of at least one interfering substance from a fluid sample with a glucose monitor and a biosensor, the method comprising the steps of:

ascertaining historical data relating to the at least one interfering substance in physiological fluid samples by;

determining a historical mean concentration for the at least one interfering substance including various standards of deviations from a plurality of physiological fluid samples measured separately by a referential sensor at various glucose concentrations;

storing the historical mean concentration and values of standard deviations from the mean of the at least one interfering substance of the plurality of physiological fluid samples;

measuring current output transient of each of the plurality of the physiological fluid samples with respect to time points during a test sequence; and

obtaining historical regression of slopes and intercepts, along with coefficients of determination of the current output transient at corresponding time points with respect to a test interval for each sample of the plurality of samples; and

retaining as historical data for each time point of the current transient of each of the physiological samples, the following parameters from regression analysis as a function of the at least one interfering substance concentration at each specific glucose concentration;

(a) regression slope, (b) regression intercept, and (c) coefficient of determination associated with the regression slope and regression intercept;

depositing a physiological fluid sample in a test chamber of the biosensor to start a test sequence;

applying a plurality of potential to electrodes disposed in the test chamber of the biosensor over a time interval of the test sequence;

measuring a current output transient over a plurality of time points during the time interval of the test sequence to provide a measured current output transient for each of the plurality of time points;

estimating a glucose concentration of a fluid sample from the measured current output transient of the measuring step;

categorizing the estimated glucose concentration into one of plural distinct categories of glucose magnitudes;

estimating a plurality of at least one interfering substance concentration at specific time points based on;

(a) the measured current output transient; and

(b) historical slopes and historical intercepts of regression analysis of current transient output for at least one interfering substance historical concentrations that have been collected in the one category of glucose magnitudes;

determining an estimated mean at least one interfering substance concentration from the plurality of estimated at least one interfering substance concentrations from the estimating step;

correcting the measured current output transient based on;

(a) the measured current output transient at the specific time points during the test sequence, (b) the historical slope at the specific time points during the test sequence from historical data, and (c) historical mean of the at least one interfering substance concentration and (d) estimated mean of the at least one interfering substance concentration of the estimating step; and

calculating a glucose concentration corrected for the presence of at least one interfering substance based on the measured current output transient that includes the corrected current output transient at the specific time points from the correcting step.