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

• US 20040019431A1
• Filed: 02/12/2003
• Published: 01/29/2004
• Est. Priority Date: 12/14/2001
• Status: Active Grant

• Current Assignee: OptiScan Biomedical Corporation
• Original Assignee: Hercules Technology Growth Capital, Inc.
• Inventors: Braig, James R., Sterling, Bernhard B., Hartstein, Philip C., Goldberger, Daniel S., Gaffney, Robert D.
• Granted Patent: US 6,862,534 B2
• Time in Patent Office: Days
• US Class Current: 702/19
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157
• 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 sample, the sample comprising the analyte and a substance, 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; and

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

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 2, wherein the selected transmittance wavelength range comprises wavelengths between approximately 6 microns and approximately 6.15 microns.

7. The method of claim 2, wherein the selected transmittance wavelength range comprises wavelengths between approximately 12 microns and approximately 13 microns.

8. The method of claim 2, wherein the selected transmittance wavelength range comprises wavelengths approximately equal to 3 microns.

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

10. The method of claim 1, wherein the sample comprises blood and the selected absorption wavelength range comprises an isosbestic wavelength at which water and a whole blood protein have approximately equal absorptions.

11. The method of claim 10, wherein the selected absorption wavelength range comprises wavelengths between approximately 3.8 microns and approximately 4.4 microns.

12. The method of claim 10, wherein the selected absorption wavelength range comprises wavelengths between approximately 9 microns and approximately 10 microns.

13. The method of claim 10, wherein the whole blood protein comprises a material from the group consisting of:

hemoglobin, albumin, globulin, and ferritin.

14. 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.

15. The method of claim 14, wherein the substance comprises water.

16. The method of claim 14, wherein the reference substance absorption spectrum is corrected for temperature-dependent effects.

17. The method of claim 14, wherein the reference substance absorption spectrum is corrected for wavelength nonlinearities.

18. The method of claim 14, wherein scaling the reference substance absorption spectrum utilizes at least two wavelength ranges.

19. The method of claim 1, wherein the sample comprises a second substance, and the method further comprises subtracting a second contribution corresponding to the second substance from the corrected absorption spectrum, thereby providing a twice-corrected absorption spectrum substantially free of contribuyions from the substance and from the second substance

20. The method of claim 19, wherein subtracting the second contribution comprises:

providing a second reference absorption spectrum corresponding to the second substance;

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.

21. The method of claim 20, wherein the second substance comprises a whole blood protein.

22. The method of claim 20, wherein the second substance comprises components of a boundary layer between water and a whole blood protein.

23. The method of claim 20, wherein the second substance comprises urea or lactate.

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

25. The method of claim 24, wherein the corrected absorption spectrum is fitted with reference analyte spectral data.

26. The method of claim 25, wherein the corrected absorption spectrum is fitted with the reference analyte spectral data at a wavelength near an analyte absorption maximum.

27. The method of claim 26, wherein the analyte comprises glucose and the analyte absorption maximum corresponds to a wavelength of approximately 9.25 microns.

28. The method of claim 26, wherein the analyte comprises glucose and the analyte absorption maximum corresponds to a wavelength of approximately 9.65 microns.

29. 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.

30. A method of measuring a pathlength of a sample comprising a first component and a second component, the method comprising:

providing an absorption spectrum of the sample;

determining an absorption value of the absorption spectrum at an isosbestic wavelength at which the first component and the second component have approximately equal absorption; and

calculating the pathlength from the absorption value.

31. A method of estimating a glucose concentration of a blood sample, the method comprising:

measuring sample absorption at a plurality of wavelengths between about 4 microns and 11 microns;

subtracting a contribution to said sample absorption due to the presence of water; and

subtracting a contribution to said sample absorption due to the presence of hemoglobin.