Progressive approximation of sample analyte concentration

• US 9,933,441 B2
• Filed: 03/11/2014
• Issued: 04/03/2018
• Est. Priority Date: 03/14/2013
• 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
• Primary Examiner(s): Negin, Russell S
• Application Number:
  US14/775,070
• Publication Number:
  US 20160033537A1
• Time in Patent Office: 1,484 Days
• Field of Search: None
• 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 33/723 Glycosylated haemoglobin
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR

Abstract

Error may be introduced into an analysis by both the biosensor system used to perform the analysis and by errors in the output signal measured by the measurement device of the biosensor. For a reference sample, system error may be determined through the determination of relative error. However, during an analysis of a test sample with the measurement device of the biosensor system, true relative error cannot be known. A pseudo-reference concentration determined during the analysis may be used as a substitute for true relative error. The closer the analysis-determined pseudo-reference analyte concentration is to the reference analyte concentration of the test sample, the more accurate and/or precise the analyte concentration determined by the measurement device using an anchor parameter during compensation. The present invention provides an improvement in the accuracy and/or precision of the analysis determined pseudo-reference concentration through progressive approximation.

Claims

1. A method for determining an analyte concentration in a sample using a biosensor, comprising:

generating at least two analyte responsive output signals from a sample;

measuring the two analyte responsive output signals from the sample;

determining at least two initial analyte concentrations from the two analyte responsive output signals;

determining a first pseudo-reference concentration from the two analyte responsive output signals, the first pseudo-reference concentration being a first substitute for true relative error;

determining at least two first anchor parameters in response to the first pseudo-reference concentration, the two first anchor parameters compensating for system error, at least one of the two first anchor parameters being a first channel signal-based anchor parameter determined in response to a first normalized output signal and a pseudo-reference signal, the first channel signal-based anchor parameter=(NR_OSV1−

NR_Pseudo)/NR_Pseudo, NR_OSV1 being a first normalized output signal value and NR_Pseudo being a pseudo-reference signal;

incorporating the two first anchor parameters into at least two first compensation relationships, at least one of the two first compensation relationships including Ach1_comp=Ach1initial/(1+RECh1), Ch1 being channel 1, Ach1_comp being the anchor parameter compensated analyte concentration determined for channel 1, Ach1 initial being the initial analyte concentration determined for channel 1;

determining at least two first anchor compensated analyte concentrations in response to the two initial analyte concentrations, the two first anchor parameters, and the two first compensation relationships;

determining a second pseudo-reference concentration by averaging the two first anchor compensated analyte concentrations, the second pseudo-reference concentration being a second substitute for true relative error; and

reporting the second pseudo-reference concentration as a final compensated analyte concentration of the sample.

2. The method of claim 1, further comprising:

determining at least two second anchor parameters in response to the second pseudo-reference concentration, the two second anchor parameters compensating for system error;

incorporating the two second anchor parameters into at least two second compensation relationships;

determining at least two second anchor compensated analyte concentrations in response to the two initial analyte concentrations, the two second anchor parameters, and the two second compensation relationships;

determining a third pseudo-reference concentration by averaging the two second anchor compensated analyte concentrations, the third pseudo-reference concentration being a third substitute for true relative error; and

reporting the third pseudo-reference concentration as the final compensated analyte concentration of the sample.

3. The method of claim 2, further comprising:

determining at least two third anchor parameters in response to the third pseudo-reference concentration, the one two third anchor parameters compensating for system error;

incorporating the one two third anchor parameters into at least two third compensation relationships;

determining at least two third anchor compensated analyte concentrations in response to the two initial analyte concentrations, the two third anchor parameters, and the two third compensation relationships;

determining a fourth pseudo-reference concentration by averaging the two third anchor compensated analyte concentrations, the fourth pseudo-reference concentration being a fourth substitute for true relative error; and

reporting the fourth pseudo-reference concentration as the final compensated analyte concentration of the sample.

4. The method of claim 1, wherein the determining of the first pseudo-reference concentration includes comprises averaging the at least two analyte responsive output signals.

5. The method of claim 1, wherein the determining of the first pseudo-reference concentration includes:

averaging the two analyte responsive output signals; and

converting an averaged signal of the two analyte responsive output signals into the second pseudo-reference concentration.

6. The method claim 1, wherein the two first anchor parameters include comprises at least one concentration-based anchor parameter.

7. The method of claim 6, further comprising determining the concentration-based anchor parameter by subtracting the first pseudo-reference concentration from one of the two initial analyte concentrations and dividing by the first pseudo-reference concentration.

8. The method of claim 1, wherein the determining of the two first anchor parameters includes comprises:

determining a second channel signal-based anchor parameter in response to a second normalized output signal value and the pseudo-reference signal.

9. The method of claim 8,

wherein the second channel signal-based anchor parameter includes a second signal anchor parameter=(NR_OSV2−

NR_Pseudo)/NR_Pseudo, NR_OSV2 being the second normalized output signal value and NR_Pseudo being the pseudo-reference signal value.

10. The method of claim 8, further comprising:

determining the first normalized output signal value in response to a first analyte responsive output signal and a normalizing relationship,

determining the second normalized output signal value in response to a second analyte responsive output signal and the normalizing relationship; and

determining the pseudo-reference signal in response to the pseudo-reference concentration and a normalized reference correlation.

11. The method of claim 1, wherein the two first compensation relationships further include:

Ach3_comp=Ach3initial/(1+RECh3), Ch3 being channel 3, Ach3_comp being the anchor parameter compensated analyte concentration determined for channel 3, Ach3initial being the initial analyte concentration determined for channel 3, and RECh3 being the compensation relationship as determined for channel 3.

12. The method of claim 1, wherein the final compensated analyte concentration includes comprises at least one of glycated hemoglobin and glucose, and where the sample including comprises blood.

13. A biosensor system for determining an analyte concentration in a sample, comprising:

a test sensor having a sample interface adjacent to a reservoir formed by a base, where the test sensor is capable of generating at least two analyte responsive output signals from a sample; and

a measurement device having a processor connected to a sensor interface, the sensor interface having electrical communication with the sample interface, and the processor having electrical communication with a storage medium;

wherein the processor is capable of measuring the two analyte responsive output signals from the sample;

wherein the processor is capable of determining at least two initial analyte concentrations from the two analyte responsive output signals;

wherein the processor is capable of determining a first pseudo-reference concentration from the two analyte responsive output signals, the first pseudo-reference concentration being a first substitute for true relative error;

wherein the processor is capable of determining at least two first anchor parameters in response to the first pseudo-reference concentration, the two first anchor parameters compensating for system error, at least one of the two first anchor parameters being a first channel signal-based anchor parameter determined in response to a first normalized output signal and a pseudo-reference signal, the first channel signal-based anchor parameter=(NR_OSV1−

NR_Pseudo)/NR_Pseudo, NR_OSV1 being a first normalized output signal value and NR_Pseudo being a pseudo-reference signal;

wherein the processor is capable of incorporating the two first anchor parameters into at least two first compensation relationships, at least one of the two first compensation relationships including Ach1_comp=Ach1initial/(1+RECh1), Ch1 being channel 1, Ach1_comp being the anchor parameter compensated analyte concentration determined for channel 1, Ach1 initial being the initial analyte concentration determined for channel 1;

wherein the processor is capable of determining at least two first anchor compensated analyte concentrations in response to the two initial analyte concentrations, the two first anchor parameters, and the two first compensation relationships;

wherein the processor is capable of determining a second pseudo-reference concentration by averaging the two first anchor compensated analyte concentrations, the second pseudo-reference concentration being a second substitute for true relative error; and

wherein the processor is capable of reporting the second pseudo-reference concentration as a final compensated analyte concentration of the sample.

14. The biosensor system of claim 13, further comprising:

wherein the processor is capable of determining at least two second anchor parameters in response to the second pseudo-reference concentration, the two second anchor parameters compensating for system error;

wherein the processor is capable of incorporating the two second anchor parameters into at least two second compensation relationships;

wherein the processor is capable of determining at least two second anchor compensated analyte concentrations in response to the two initial analyte concentrations, the two second anchor parameters, and the two second compensation relationships;

wherein the processor is capable of determining a third pseudo-reference concentration by averaging the two second anchor compensated analyte concentrations, the third pseudo-reference concentration being a third substitute for true relative error; and

wherein the processor is capable of reporting the third pseudo-reference concentration as the final compensated analyte concentration of the sample.

15. The biosensor system of claim 14, further comprising:

wherein the processor is capable of determining at least two third anchor parameters in response to the third pseudo-reference concentration, the two third anchor parameters compensating for system error;

wherein the processor is capable of incorporating the two third anchor parameters into at least two third compensation relationships;

wherein the processor is capable of determining at least two third anchor compensated analyte concentrations in response to the two initial analyte concentrations, the two third anchor parameters, and the two third compensation relationships;

wherein the processor is capable of determining a fourth pseudo-reference concentration by averaging the two third anchor compensated analyte concentrations, the fourth pseudo-reference concentration being a fourth substitute for true relative error; and

wherein the processor is capable of reporting the fourth pseudo-reference concentration as the final compensated analyte concentration of the sample.

16. The biosensor system of claim 13, wherein the two analyte responsive output signals are independent analyte responsive output signals from the sample.

17. The biosensor system of claim 13, wherein the processor is capable of determining a third pseudo-reference concentration by selecting a sample analyte concentration value as the pseudo-reference concentration, wherein the sample analyte concentration value for multiple analyses is on average closer to an actual analyte concentration of the sample than would be independently determined from the two analyte responsive output signals.

18. The biosensor system of claim 17, wherein the processor is capable of determining a first pseudo-reference concentration by averaging the two analyte responsive output signals.

19. The biosensor system of claim 13, wherein the processor is capable of storing the final compensated analyte compensation in the storage medium.

20. A biosensor system for determining an analyte concentration in a sample, comprising:

a test sensor having a sample interface adjacent to a reservoir formed by a base, where the test sensor is capable of generating at least two analyte responsive output signals from a sample; and

a measurement device having a processor connected to a sensor interface, the sensor interface having electrical communication with the sample interface, and the processor having electrical communication with a storage medium;

wherein the processor is capable of measuring the two analyte responsive output signals from the sample;

wherein the processor is capable of determining at least two initial analyte concentrations from the two analyte responsive output signals;

wherein the processor is capable of determining a first pseudo-reference concentration from the two analyte responsive output signals, the first pseudo-reference concentration being a first substitute for true relative error;

wherein the processor is capable of determining at least two first anchor parameters in response to the first pseudo-reference concentration, the two first anchor parameters compensating for system error;

wherein the processor is capable of incorporating the two first anchor parameters into at least two first compensation relationships;

wherein the processor is capable of determining at least two first anchor compensated analyte concentrations in response to the two initial analyte concentrations, the two first anchor parameters, and the two first compensation relationships;

wherein the processor is capable of determining a second pseudo-reference concentration by averaging the two first anchor compensated analyte concentrations, the second pseudo-reference concentration being a second substitute for true relative error;

wherein the processor is capable of determining a third pseudo-reference concentration by selecting a sample analyte concentration value as the pseudo-reference concentration;

wherein the sample analyte concentration value for multiple analyses is on average closer to an actual analyte concentration of the sample than would be independently determined from the two analyte responsive output signals; and

wherein the processor is capable of reporting the third pseudo-reference concentration as a final compensated analyte concentration of the sample.