Residual compensation including underfill error

• US 10,591,436 B2
• Filed: 03/22/2011
• Issued: 03/17/2020
• Est. Priority Date: 03/22/2010
• 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, Harrison, Bern, Maurer, Eric
• Primary Examiner(s): Zeman, Mary K
• Application Number:
  US13/053,722
• Publication Number:
  US 20110231105A1
• Time in Patent Office: 3,283 Days
• 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

A biosensor system determines analyte concentration from an output signal generated from a light-identifiable species or a redox reaction of the analyte. The biosensor system compensates at least 50% of the total error in the output signal with a primary function and compensates a portion of the remaining error with a residual function. The amount of error compensation provided by the primary and residual functions may be adjusted with a weighing coefficient. The compensation method including a primary function and a residual function may be used to determine analyte concentrations having improved accuracy from output signals including components attributable to error.

Claims

1. A method of operating a biosensor system for determining an analyte concentration in a biological fluid sample when at least one operating condition error is introduced into an analysis by user self-testing, the method comprising:

providing a biosensor system in the form of an analytical instrument including

a measurement device having electrical circuitry communicatively coupled to a processor, a storage medium, a signal generator, and a sensor interface, the processor having instructions and data stored in the storage medium, and

a test sensor having a base and a sample interface, the base forming a reservoir and a channel with an opening, the base further having a surface on which at least one working electrode and at least one counter electrode are disposed, the reservoir being in electrical or optical communication with the measurement device, the sample interface having conductors connected to the working electrode and the counter electrode;

determining in a controlled environment, prior to the user self-testing, a primary error of an uncompensated analyte concentration, the primary error being at least 50% of a total error of the uncompensated analyte concentration and including at least one of a temperature error or a hematocrit error; and

subsequently and outside the controlled environment, initiating the user self-testing via the biosensor system to determine a compensated analyte concentration, the user self-testing including;

receiving the biological fluid sample in the opening, the biological fluid sample flowing through the channel to fill at least in part the reservoir of the test sensor,

introducing the operating condition error during the user self-testing but prior to determining the compensated analyte concentration in the biological fluid sample,

in response to receiving the biological fluid sample in the reservoir, generating an input signal, by the processor, from the signal generator,

transmitting the input signal by the sensor interface to the sample interface for applying the input signal to the biological fluid sample,

in response to the input signal and the uncompensated analyte concentration, receiving and measuring, by the processor, an output signal from the working electrode and the counter electrode of the test sensor,

compensating, by the processor, the primary error in the output signal with a primary function, the primary function being in the form of an index function that is determined using error parameter values from an analyte analysis or from a source independent of an analyte responsive output signal,

compensating, by the processor, a remaining error of the total error in the output signal with a first residual function, the first residual function compensating the remaining error until errors become random, the remaining error being the operating condition error,

determining a compensated output signal based on the compensating of the primary error and the remaining error in the output signal, and

determining, by the processor, the compensated analyte concentration in the biological fluid sample from the compensated output signal in which the total error has been reduced by compensating for the primary error and the remaining error.

2. The method of claim 1, further comprising determining at least one reference correlation with a reference instrument in the controlled environment prior to determining the compensated analyte concentration in the biological fluid sample.

3. The method of claim 1, further comprising adjusting the compensation provided by the first residual function with a first weighing coefficient, the first weighing coefficient being responsive to the compensation provided by the primary function.

4. The method of claim 3, further comprising compensating the output signal with a second residual function to determine a further compensated output signal, the second residual function being for further compensating residual errors remaining after application of the first residual function.

5. The method of claim 4, further comprising adjusting the compensation provided by the second residual function with a second weighing coefficient, the second weighing coefficient being responsive to the compensation provided by the first residual function.

6. The method of claim 1, wherein the first residual function compensates at least 5% of the total error in the output signal.

7. The method of claim 1, further comprising determining the first residual function by:

selecting multiple error parameters as potential terms in the first residual function, the error parameters being any value responsive to one or more errors in the output signal;

determining a first exclusion value for the potential terms;

applying an exclusion test responsive to the first exclusion value for the potential terms;

identifying one or more of the potential terms for exclusion from the first residual function; and

excluding one or more identified potential terms from the first residual function.

8. The method of claim 1, further comprising:

determining if the test sensor is filled more than once with the biological fluid sample before the output signal is generated; and

determining the compensated output signal from a different first residual function if the test sensor is filled more than once.

9. The method of claim 1, wherein the biological fluid sample is a whole blood sample and an analyte of the compensated analyte concentration is glucose, the determining of the compensated analyte concentration in the biological fluid sample from the compensated output signal reducing the slope of a correlation plot representing hematocrit sensitivity in whole blood to ±

0.4 or less when the whole blood sample has a hematocrit level from about 30% to about 55%.

10. The method of claim 1, wherein the compensated analyte concentration is determined from at least a forty-sample self-testing test case, and wherein the test case has a measurement performance of at least one of

at least 85% of the determined uncompensated analyte concentrations being within a ±

10% percent bias limit,

at least 95% of the determined uncompensated analyte concentrations being within a ±

8% percent bias limit, and

at least 60% of the determined uncompensated analyte concentrations being within a +5% percent bias limit.

11. The method of claim 1, wherein the compensated analyte concentration is determined from at least a 5,000-sample test case, the test case being at least one of a self-testing test case and a health care professional test case, the test case using test sensors from between two and 45 test-sensor lots, the test case having a measurement performance of at least one of

the determined uncompensated analyte concentrations having an average percent bias standard deviation value of less than five,

at least 90% of the determined uncompensated analyte concentrations being within a ±

10% percent bias, and

the determined uncompensated analyte concentrations having a mean percent bias spread within about +12%.

12. The method of claim 1, wherein the compensated analyte concentration lacks at least 60% of the total error of the output signal.

13. The method of claim 1, wherein a mean percent bias of the compensated analyte concentrations determined from the compensated output signal from different lots of test sensors is at least 47% less than a mean percent bias determined from the output signal for uncompensated analyte concentrations determined from the different lots of test sensors.

14. The method of claim 1, further comprising reducing to +5% or less the difference between uncompensated analyte concentrations determined from test sensors stored for four weeks at −

20°

C. and uncompensated analyte concentrations determined from test sensors stored for four weeks at 50°

C.

15. The method of claim 8, wherein 90% or more of the determined uncompensated analyte concentrations are within a +10% percent bias limit when the test sensors are filled more than once with the sample before the output signal is generated.