Method of determining an analyte concentration in a sample from an absorption spectrum

• US 7,096,124 B2
• Filed: 02/18/2005
• Issued: 08/22/2006
• Est. Priority Date: 12/14/2001
• Status: Expired due to Fees

• Current Assignee: OptiScan Biomedical Corporation
• Original Assignee: OptiScan Biomedical Corporation
• Inventors: Braig, James R., Sterling, Bernhard B., Goldberger, Daniel S., Witte, Kenneth G.
• Primary Examiner(s): Barlow, John
• Assistant Examiner(s): Washburn, Douglas N.
• Application Number:
  US11/062,110
• Publication Number:
  US 20050197790A1
• Time in Patent Office: 550 Days
• Field of Search: 356/306, 702/22, 702/23, 702/31
• US Class Current: 702/23
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157 disposable multilayered or laminated electrodes G01N27/307; details of handling chemical test elements G01N33/4875
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: G01N 21/274 Calibration, base line adjustment, drift correction
• CPC Class Codes: G01N 21/314 with comparison of measurements at specific and non-specific wavelengths dual wavelength spectrometry G01J3/427
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence
• 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

Abstract

A method determines an analyte concentration in a sample including the analyte and a substance. The method includes providing an absorption spectrum of the sample. The absorption spectrum has an absorption baseline. The method further includes shifting the absorption spectrum so that the absorption baseline approximately equals a selected absorption value in a selected absorption wavelength range. The method further includes subtracting a substance contribution from the absorption spectrum. Thus, the method provides a corrected absorption spectrum substantially free of a contribution from the substance.

Claims

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

providing an absorption spectrum of the sample, the absorption spectrum having an absorption baseline;

shifting the absorption spectrum so that the absorption baseline approximately equals a selected absorption value in a selected absorption wavelength range at or near an isobestic wavelength at which both water and the protein have substantially the same absorbance; and

subtracting a water contribution from the absorption spectrum, thereby providing a corrected absorption spectrum substantially free of a contribution from the water.

2. The method of claim 1, wherein providing the absorption spectrum comprises:

providing a transmittance spectrum of the sample, the transmittance spectrum having a transmittance baseline;

shifting the transmittance spectrum so that the transmittance baseline approximately equals zero in a selected transmittance wavelength range; and

determining the absorption spectrum from the transmittance spectrum.

3. The method of claim 2, wherein providing the transmittance spectrum of the sample comprises:

transmitting at least a portion of an infrared signal through the sample, the infrared signal comprising a plurality of wavelengths; and

measuring the portion of the infrared signal transmitted through the sample as a function of wavelength.

4. The method of claim 3, wherein providing the transmittance spectrum further comprises placing the sample in a cuvette.

5. The method of claim 2, wherein the sample comprises blood, the analyte comprises glucose, and the selected transmittance wavelength range comprises wavelengths at which the transmittance spectrum is dominated by water transmittance.

6. The method of claim 1, wherein the selected absorption value is approximately equal to zero.

7. The method of claim 1, wherein the protein comprises a material from the group consisting of:

hemoglobin, albumin, globulin, and ferritin.

8. The method of claim 1, wherein subtracting the substance contribution comprises:

providing a reference substance absorption spectrum;

scaling the reference substance absorption spectrum by multiplying the reference substance absorption spectrum by a scaling factor; and

subtracting the scaled reference substance absorption spectrum from the absorption spectrum, thereby providing the corrected absorption spectrum.

9. The method of claim 8, wherein the reference substance absorption spectrum is corrected for temperature-dependent effects.

10. The method of claim 8, wherein the reference substance absorption spectrum is corrected for wavelength nonlinearities.

11. The method of claim 8, wherein scaling the reference substance absorption spectrum utilizes at least two wavelength ranges.

12. The method of claim 1, further comprising subtracting a protein contribution corresponding to the protein from the corrected absorption spectrum, thereby providing a twice-corrected absorption spectrum substantially free of contributions from water and from the protein.

13. The method of claim 12, wherein subtracting the protein contribution comprises:

providing a second reference absorption spectrum corresponding to the protein;

scaling the second reference absorption spectrum by multiplying the second reference absorption spectrum by a second scaling factor; and

subtracting the scaled second reference absorption spectrum from the corrected absorption spectrum, thereby providing the twice-corrected absorption spectrum.

14. The method of claim 8, further comprising fitting the corrected absorption spectrum with analyte spectral data, thereby yielding a measurement of the analyte concentration in the sample.

15. The method of claim 14, wherein the corrected absorption spectrum is fitted with reference analyte spectral data.

16. The method of claim 15, wherein the corrected absorption spectrum is fitted with the reference analyte spectral data at a wavelength near an analyte absorption maximum.

17. The method of claim 16, wherein the analyte comprises glucose and the analyte absorption maximum corresponds to a wavelength of approximately 9.25 microns.

18. The method of claim 16, wherein the analyte comprises glucose and the analyte absorption maximum corresponds to a wavelength of approximately 9.65 microns.

19. A method of providing pathlength-insensitive measurements of blood constituents in a sample using infrared (IR) spectroscopy, the method comprising:

providing an absorption spectrum of the sample, the absorption spectrum having an absorption baseline; and

shifting the absorption spectrum so that the absorption baseline approximately equals a selected absorption value in an absorption wavelength range comprising an isosbestic wavelength at which water and a whole blood protein have approximately equal absorptions.

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

providing a cuvette;

filling the cuvette with saline and measuring a reference absorbance spectrum of the cuvette containing the saline;

filling the cuvette with the biological sample and measuring a sample absorbance spectrum of the cuvette containing the biological sample;

shifting the sample absorbance spectrum so that an absorption baseline approximately equals a selected absorption value in a selected absorption wavelength range;

and calculating the analyte concentration in the biological sample using the reference absorbance spectrum and the sample absorbance spectrum.

21. The method of claim 20, wherein filling the cuvette with saline and measuring the reference absorbance spectrum is performed prior to filling the cuvette with the biological sample and measuring the sample absorbance spectrum.

22. The method of claim 21, further comprising filling the cuvette with saline and measuring the reference absorbance spectrum after filling the cuvette with the biological sample and measuring the sample absorbance spectrum.

23. The method of claim 20, wherein filling the cuvette with saline and measuring the reference absorbance spectrum is performed after filling the cuvette with the biological sample and measuring the sample absorbance spectrum.

24. The method of claim 20, wherein calculating the analyte concentration comprises calculating an optical pathlength of the cuvette.

25. The method of claim 20, wherein calculating the analyte concentration comprises calculating instrument drift and baseline deviations using the reference absorbance spectrum.