Method of determining analyte concentration in a sample using infrared transmission data

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

providing absorption data of the sample;

providing reference absorption data of the substance;

calculating a substance contribution of the absorption data, wherein calculating the substance contribution comprises scaling the reference absorption data by multiplying the reference absorption data by a scaling factor, the scaling factor allowing for calculation of a pathlength-independent quality;

subtracting the substance contribution from the absorption data of the sample, thereby providing corrected absorption data of the analyte substantially free of a contribution from the substance;

using the corrected absorption data to calculate analyte concentration in the sample; and

providing the analyte concentration to a user.

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

providing transmittance data of the sample; and

determining the absorption data from the transmittance data.

3. The method of claim 2 , wherein providing the transmittance data 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 data further comprises placing the sample in a cuvette.

5. The method of claim 2 , wherein the sample comprises blood.

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

7. The method of claim 2 , wherein the sample comprises plasma.

8. The method of claim 7 , wherein the analyte comprises glucose, and the selected transmittance wavelength range comprises wavelengths at which the transmittance data is dominated by water transmittance.

9. The method of claim 1 , wherein the substance comprises water.

10. The method of claim 1 , wherein the substance interferes with determining the analyte concentration.

11. The method of claim 10 , wherein the sample further comprises a second substance which interferes with determining the analyte concentration to a lesser extent than does the substance, the method further comprising calculating a second substance contribution of the absorption data and subtracting the second substance contribution from the absorption data, thereby providing twice-corrected absorption data substantially free of contributions from the substance and from the second substance.

12. The method of claim 1 , wherein the reference absorption data is corrected for temperature-dependent effects.

13. A method of determining an analyte concentration in a sample, the sample comprising the analyte and a substance, the method comprising:

providing absorption data of the sample;

providing reference absorption data of the substance;

calculating a substance contribution of the absorption data, wherein calculating the substance contribution comprises scaling the reference absorption data by multiplying the reference absorption data by a scaling factor;

subtracting the substance contribution from the absorption data of the sample, thereby providing corrected absorption data of the analyte substantially free of a contribution from the substance, wherein the reference absorption data is corrected for wavelength-dependent nonlinearities; and

storing the corrected absorption data in a memory.

14. The method of claim 13 , wherein the sample is contained within a sample element and the wavelength-dependent nonlinearities are generated by scattering from the sample element.

15. The method of claim 13 , wherein the sample is contained within a sample element and the wavelength-dependent nonlinearities are generated by fringing from the sample element.

16. The method of claim 1 , wherein scaling the reference absorption data utilizes at least two wavelength ranges.

17. 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 data, thereby providing twice-corrected absorption data substantially free of contributions from the substance and from the second substance.

18. The method of claim 17 , wherein subtracting the second contribution comprises:

providing second reference absorption data corresponding to the second substance;

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

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

19. The method of claim 18 , wherein the second substance comprises a whole blood protein.

20. The method of claim 18 , wherein the second substance comprises components of a boundary layer between water and a whole blood protein.

21. The method of claim 18 , wherein the second substance comprises urea or lactate.

22. The method of claim 17 , further comprising fitting the twice-corrected absorption data with analyte spectral data, thereby yielding a measurement of the analyte concentration in the sample.

23. The method of claim 22 , wherein the twice-corrected absorption data is fitted with reference analyte spectral data.

24. A method of providing measurements of constituents in a sample using infrared (IR) spectroscopy, the method comprising:

providing absorption data of the sample, wherein providing absorption data comprises:

placing the sample in a cuvette having a shape;

passing IR radiation through a filter having a finite width;

irradiating the cuvette with the IR radiation; and

detecting a fraction of the IR radiation transmitted through the cuvette and the sample;

correcting the absorption data for a non-analyte contribution to the absorption data, wherein the non-analyte contribution is from the finite width of the filter; and providing the corrected absorption data to a user.

25. A method of providing measurements of constituents in a sample using infrared (IR) spectroscopy, the method comprising:

providing absorption data of the sample, wherein providing absorption data comprises:

placing the sample in a cuvette having a shape;

passing IR radiation through a filter having a finite width;

irradiating the cuvette with the IR radiation; and

detecting a fraction of the IR radiation transmitted through the cuvette and the sample;

correcting the absorption data for a non-analyte contribution to the absorption data, wherein the non-analyte contribution is from the shape of the cuvette; and

storing the corrected absorption data in a memory.

26. The method of claim 25 , wherein the sample comprises blood.

27. The method of claim 25 , wherein the sample comprises plasma.

28. A method of using infrared (IR) spectroscopy to determine a ratio of an analyte volume to the total volume of a sample comprising the analyte, a first substance, and a second substance, the method comprising:

providing absorption data from the sample for a first set of wavelengths in a wavelength region where a first-substance absorption dominates;

calculating a first quantity equal to the product of a first-substance volume concentration and a path length of the sample;

providing absorption data from the sample for a second set of wavelengths in a wavelength region where the first-substance absorption and a second-substance absorption dominate;

calculating a second quantity equal to the product of a second-substance volume concentration and the path length of the sample;

providing absorption data from the sample for a third set of wavelengths in a wavelength region where the first-substance absorption, the second-substance absorption, and an analyte absorption dominate;

calculating a third quantity equal to the product of an analyte volume concentration and the path length of the sample;

calculating a ratio of the third quantity divided by the sum of the first quantity, the second quantity, and the third quantity to achieve a pathlength-independent quantity; and

storing the ratio in a memory.

29. The method of claim 28 , wherein the analyte comprises glucose.

30. The method of claim 28 , wherein the first substance comprises water.

31. The method of claim 28 , wherein the second substance comprises hematocrit soup.

32. The method of claim 28 , wherein the second substance comprises hemoglobin.

33. The method of claim 28 , wherein the second substance comprises red blood cells.

34. A method of determining non-analyte contributions to absorption data from a sample, the method comprising:

(a) inputting transmission measurements, filter parameters, and water spectral properties;

(b) calculating optical densities and filter constants;

(c) estimating non-linear filter terms and cuvette distortion matrix elements;

(d) solving for a temperature change as a function of the path length; and

(e) calculating new estimates of absorption and non-linear terms.

35. The method of claim 34 , further comprising repeating (d) and (e) until the solution converges to a desired accuracy.

36. The method of claim 34 , wherein the sample comprises blood.

37. The method of claim 34 , wherein the sample comprises plasma.

38. A method of determining non-analyte contributions to absorption data from a sample, the method comprising:

(a) inputting transmission measurements, filter parameters, and water spectral properties;

(b) calculating optical densities and filter constants;

(c) estimating non-linear filter terms and cuvette distortion matrix elements;

(d) solving for a temperature change as a function of the path length; and

(e) calculating new estimates of absorption and non-linear terms.

39. The method of claim 38 , further comprising repeating (d) and (e) until the solution converges to a desired accuracy.

40. A method of evaluating analyte concentration errors in absorption data from a sample, the method comprising:

calculating transmission and optical densities at four wavelengths for a water-filled cuvette, the four wavelengths comprising two wavelengths dominated by absorption by water, an analyte reference wavelength, and a measurement wavelength;

using the optical densities to determine the water content at the analyte reference wavelength and the measurement wavelength;

calculating expected optical density values at the analyte reference wavelength and the measurement wavelength;

calculating residuals between the exact and calculated optical densities at the analyte reference wavelength and the measurement wavelength;

determining the analyte concentration error by calculating the analyte concentration consistent with the difference between the residuals at the analyte reference wavelength and the measurement wavelength; and

storing the analyte concentration error in a memory.

41. The method of claim 40 , wherein the sample comprises blood.

42. The method of claim 40 , wherein the sample comprises plasma.

43. The method of claim 40 , wherein the analyte comprises glucose.