Method and apparatus for minimizing spectral effects attributable to tissue state variations during NIR-based non-invasive blood analyte determination

• US 6,640,117 B2
• Filed: 09/17/2001
• Issued: 10/28/2003
• Est. Priority Date: 09/26/2000
• Status: Expired due to Term

• Current Assignee: GLT Acquisition Corporation
• Original Assignee: Sensys Medical, Inc. (Sensys Medical Limited)
• Inventors: Ruchti, Timothy L., Monfre, Stephen L., Blank, Thomas B., Mattu, Mutua, Makarewicz, Marcy R.
• Primary Examiner(s): Hindenburg, Max F.
• Assistant Examiner(s): MCCROSKY, DAVID J
• Application Number:
  US09/955,531
• Publication Number:
  US 20020038080A1
• Time in Patent Office: 771 Days
• Field of Search: 600/310, 600/326, 600/322, 600/323, 600/334, 600/474-477, 600/549, 356/43, 374/161, 374/121
• US Class Current: 600/322
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1491 Heated applicators
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes

Abstract

A method and apparatus for minimizing confounding effects in a noninvasive in-vivo spectral measurement caused by fluctuations in tissue state monitors a selected tissue state parameter spectroscopically and maintains the selected parameter within a target range, at which spectral effects attributable to the changes in the selected parameter are minimized. The invention includes both active and passive control. A preferred embodiment of the invention provides a method and apparatus for minimizing the confounding effects in near IR spectral measurements attributable to shifts in skin temperature at a tissue measurement site. Spectroscopic monitoring of skin temperature at the measurement site provides near-instantaneous temperature readings by eliminating thermal time constants. A thermistor positioned at the measurement site provides active control. The spectrometer and the temperature control device are incorporated into a single instrument for noninvasive measurement of blood glucose concentration.

Claims

1. A method for controlling spectral effects attributable to tissue state variations during NIR-based, non-invasive blood analyte determination, comprising the steps of:

determining a target range of values for a selected tissue state parameter, said tissue state parameter comprising skin temperature in the vicinity of a tissue measurement site on a body part of a live subject;

providing means for modifying said tissue state parameter;

providing a calibration model, developed using a calibration data set that includes spectral measurements on a group of exemplary subjects combined with associated skin temperature reference measurements, said calibration developed using multivariate analytical techniques, that correlates said spectral effects to variations in said tissue state parameter, said spectral effects comprising shifts in a peak water absorbance band in an NIP spectrum, wherein said model implicitly incorporates said shift information in multivariate regression coefficients;

monitoring said tissue state parameter by measuring an NIR spectrum and calculating values for said parameter from said spectrum according to said calibration model; and

if said calculated value is outside of said target range, modifying said

tissue state parameter until a measured value for said parameter is within said target range.

2. The method of claim 1, wherein said peak water absorbance band shifts to shorter wavelengths as skin temperature increases and wherein said peak water absorbance band shifts to longer wavelengths as skin temperature decreases;

wherein said shifts attenuate a net analyte signal.

3. The method of claim 2, wherein said peak water absorbance band occurs in a wavelength region at approximately 1450 nm.

4. The method of claim 2, wherein said step of determining a target range comprises:

empirically determining said target range by examining spectra from a calibration data set to determine a temperature range in which said shifts are minimized.

5. The method of claim 1, wherein said target range comprises a range of skin temperatures wherein said shifts are minimized, so that said attenuation of said net analyte signal is minimized.

6. The method of claim 5, wherein said target range is approximately eighty-nine to ninety one degrees, Fahrenheit.

7. The method of claim 1, wherein said means for modifying a tissue state parameter comprises one or both of:

means for actively controlling said skin temperature; and

means for passively controlling said skin temperature.

8. The method of claim 7, wherein said active means and said passive means are employed in complementary fashion to maintain skin within said target range.

9. The method of claim 8, wherein said active means of control is employed to induce rapid changes in skin temperature.

10. The method of claim 7, wherein said passive means of control is employed for extended time periods.

11. The method of claim 7, wherein said means for passively controlling said skin temperature comprises a thermal wrap applied to said body part, wherein initial application of said thermal wrap causes a rise in skin temperature.

12. The method of claim 11, wherein skin temperature is maintained within said target range by one of loosening, tightening and removing said thermal wrap.

13. The method of claim 7, wherein said means for actively controlling said skin temperature comprises a temperature-controlled heat sink.

14. The method of claim 13, wherein said heat sink has a set point within said target range, and wherein said heat sink cools or warms said skin to maintain skin temperature within said target range.

15. The method of claim 13, wherein active control is localized to skin that comes into contact with said heat sink.

16. The method of claim 7, wherein said step of modifying said tissue state parameter comprises applying one or both of said means of control so that skin temperature is restored to said target range.

17. The method of claim 1, wherein said reference measurements span a range approximately equal to or greater than said target range.

18. The method of claim 1, wherein said reference measurements are made using a noninvasive temperature sensor placed in the immediate vicinity of the tissue measurement site.

19. The method of claim 1, wherein said step of monitoring said tissue state parameter comprises the steps of:

calculating an absorbance spectrum from said NIR spectrum;

pre-processing said absorbance spectrum; and

calculating a skin temperature value by applying said multivariate calibration model.

20. An apparatus for controlling spectral effects attributable to tissue state variations during NIR-based, non-invasive blood analyte determination, comprising:

means for modifying a selected tissue state parameter, wherein said tissue state parameter comprises skin temperature in the vicinity of a tissue measurement site on a body part of a live subject;

means for measuring an NIR spectrum at a tissue measurement site;

a calibration model that correlates said spectral effects to variations in said tissue state parameter, wherein said calibration model is developed using a calibration data set that includes spectral measurements or a group of exemplary subjects combined with associated skin temperature reference measurements, said spectral effects comprising shifts in a peak water absorbance band in an NIR spectrum;

means for monitoring said tissue state parameter by measuring an NIR spectrum and calculating values for said parameter from said spectrum according to said calibration model;

wherein said tissue state parameter is modified by said modifying means if said calculated value is outside of a target range until said parameter is within said target range.

21. The apparatus of claim 20, wherein said peak water absorbance band shifts to shorter wavelengths as skin temperature increases and wherein said peak water absorbance band shifts to longer wavelengths as skin temperature decreases;

wherein said shifts attenuate a net analyte signal.

22. The apparatus of claim 21, wherein said peak water absorbance band occurs in a wavelength region at approximately 1450 nm.

23. The apparatus of claim 21, wherein said target range comprises a range of skin temperatures wherein said shifts are minimized, so that said attenuation of said net analyte signal is minimized.

24. The apparatus of claim 21, wherein target range is empirically determined by examining spectra from a calibration data set to determine a temperature range in which said shifts are minimized.

25. The apparatus of claim 20, wherein said target range is approximately eighty-nine to ninety one degrees, Fahrenheit.

26. The apparatus of claim 20, wherein said means for modifying a tissue state parameter comprises one or both of:

means for actively controlling said skin temperature; and

means for passively controlling said skin temperature.

27. The apparatus of claim 26, wherein said active means and said passive means are employed in complementary fashion to maintain skin within said target range.

28. The apparatus of claim 27, wherein said active means of control is employed to induce rapid changes in skin temperature.

29. The apparatus of claim 26, wherein said passive means of control is employed for extended time periods.

30. The apparatus of claim 26, wherein said means for passively controlling said skin temperature comprises a thermal wrap applied to said body part, wherein initial application of said thermal wrap causes a rise in skin temperature.

31. The apparatus of claim 30, wherein skin temperature is maintained within said target range by one of loosening, tightening and removing said thermal wrap.

32. The apparatus of claim 26, wherein said means for measuring an NIR spectrum comprises a NIR spectrometer instrument, wherein said spectrometer instrument includes a subject interface module.

33. The apparatus of claim 32, wherein said means for actively controlling said skin temperature comprises a temperature-controlled heat sink.

34. The apparatus of claim 33, wherein said heat sink has a set point within said target range, and wherein said heat sink cools or warms said skin to maintain skin temperature within said target range.

35. The apparatus of claim 33, wherein active control is localized to skin that comes into contact with said heat sink.

36. The apparatus of claim 32, wherein said heat sink is incorporated into said subject interface module, so that said heat sink is in contact with said tissue measurement site during use.

37. The apparatus of claim 26, wherein said tissue state parameter is modified by applying one or both of said means of control so that skin temperature is restored to said target range.

38. The apparatus of claim 20, wherein said reference measurements span a range approximately equal to or greater than said target range.

39. The apparatus of claim 20, wherein said reference measurements are made using a noninvasive temperature sensor placed in the immediate vicinity of the tissue measurement site.

40. The apparatus of claim 20, wherein said tissue state parameter is monitored by:

calculating an absorbance spectrum from said NIR spectrum;

pre-processing said absorbance spectrum; and

calculating a skin temperature value by applying said multivariate calibration model.

41. A method for controlling spectral effects attributable to tissue state variations during NIR-based, non-invasive blood analyte determination, comprising the steps of:

determining a target range of values for a selected tissue state parameter, said tissue state parameter comprising skin temperature in the vicinity of a tissue measurement site on a body part of a live subject;

providing means for modifying said tissue state parameter;

providing a calibration model that correlates said spectral effects to variations in said tissue state parameter, said spectral effects comprising shifts in a peak water absorbance band in an NIR spectrum, said target range comprising a range of skin temperatures wherein said shifts are minimized;

monitoring said tissue state parameter by measuring an NIR spectrum and calculating values for said parameter from said spectrum according to said calibration model; and

if said calculated value is outside of said target range, modifying said

tissue state parameter until a measured value for said parameter is within said target range.