Method and apparatus for determination of analyte concentration

• US 7,952,692 B2
• Filed: 12/12/2006
• Issued: 05/31/2011
• Est. Priority Date: 12/12/2006
• Status: Active Grant

• Current Assignee: OrSense Ltd.
• Original Assignee: OrSense Ltd.
• Inventors: Primack, Harel, Weinstein, Aharon
• Primary Examiner(s): Chowdhury; Tarifur
• Assistant Examiner(s): Stock, Jr.; Gordon J
• Application Number:
  US11/637,194
• Publication Number:
  US 20080137066A1
• Time in Patent Office: 1,631 Days
• Field of Search: None
• US Class Current: 356/39
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14535 for measuring haematocrit
• 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: A61B 5/14551 for measuring blood gases
• CPC Class Codes: A61B 5/6826 Finger
• CPC Class Codes: A61B 5/6838 Clamps or clips
• CPC Class Codes: G01N 21/314 with comparison of measurements at specific and non-specific wavelengths dual wavelength spectrometry G01J3/427

Abstract

A method and system are presented for use in determination of the concentration of an analyte in a subject'"'"'s medium. The medium is irradiated with at least two radiation components to produce detectable radiation responses of the medium thereto. These at least two radiation components are selected to have different mean wavelengths and such that the spectral bandwidth of at least one of said at least two radiation components is characterized by relatively high variability of the extinction coefficient of the analyte of interest across said spectral bandwidth. This enables analysis of data indicative of detected radiation responses of the medium to said at least two radiation components and determination of the concentration of said analyte.

Claims

1. A method for use in measurements of the concentration of an analyte in a medium having a certain extinction coefficient spectrum, said method comprising:

providing a selected light source unit capable of generating at least first and second radiation components, each having a selected mean wavelength and a selected spectral bandwidth such that the mean wavelength and spectral bandwidth of said first radiation component correspond to a first spectral region of the extinction coefficient spectrum of said analyte where variation of an extinction coefficient, Δ

β

₁, per volume fraction of the analyte across the spectral bandwidth of the first radiation component is higher than in other spectral regions of the extinction coefficient spectrum, and the mean wavelength and second spectral bandwidth of said second radiation component correspond to a second spectral region of the extinction coefficient spectrum where variation of an extinction coefficient, Δ

β

₂ per volume fraction of the analyte across the spectral bandwidth of the second radiation component is smaller than in other spectral regions of the extinction coefficient spectrum, and at least one of said at least two radiation components contains a plurality of wavelengths with radiation intensities that are in a fixed relation to each other during periods of said measurements;

irradiating the medium with said at least first and second radiation components during a certain measurement time to thereby produce detectable radiation responses of the medium thereto,

analyzing data indicative of detected radiation responses of the medium to said at least first and second radiation components to determine the concentration of said analyte.

2. The method of claim 1, comprising applying at least two different sources of radiation to the medium to irradiate it by said at least two radiation components, respectively.

3. The method of claim 1, wherein said selecting of the mean wavelength of the spectral bandwidth for at least one of said at least two radiation components to be used in the measurements comprises analyzing data indicative of the extinction coefficient spectrum of the analyte of interest.

4. The method of claim 1, wherein the mean wavelength and the spectral bandwidth of at least one of said at least two radiation components are selected such that the variability of the extinction coefficient of said analyte across this spectral bandwidth is one of global and local maxima in absolute value.

5. The method of claim 1, wherein the mean wavelength of said at least two radiation components contains red-near infrared optical spectral regions.

6. The method of claim 1, wherein the mean wavelength of said at least two radiation components is within about 400 nm-2300 nm.

7. The method of claim 1, wherein the radiation responses comprise intensities of at least one of transmitted and reflected radiation through and from an irradiated part of the medium, respectively, for said at least two radiation components.

8. The method of claim 1, wherein said analyte is one of the following:

hemoglobin, hematocrit, glucose, oxygen saturation, cholesterol, albumin and bilirubin.

9. The method of claim 1, wherein said analyte is a blood analyte.

10. The method of claim 1, wherein said analyte is a tissue analyte.

11. The method of claim 1, wherein said medium is a finger.

12. The method of claim 1, wherein said medium is a fleshy body part.

13. The method of claim 1, wherein at least one of said at least two radiation components is emitted by at least one Light Emitting Diode (LED).

14. The method of claim 1, wherein at least said first radiation component is emitted by a Light Emitting Diode (LED), and at least said second radiation component is emitted by a laser source.

15. The method of claim 1, wherein at least said first radiation component is emitted by a broadband light source configured for emitting the plurality of wavelengths with radiation intensities that can be in a fixed relation to each other during the measurement time.

16. The method of claim 1, comprising detecting said radiation responses as functions of time and wavelength, analyzing data indicative thereof for said at least two radiation components to determine a measurable relation between the detected radiation responses, and analyzing said relation to determine the analyte concentration.

17. The method of claim 13, wherein at least one of said at least two radiation components is emitted by at least one monochromatic source.

18. The method of claim 14, wherein said at least one LED has the spectral bandwidth of about 20-50 nm.

19. The method of claim 15, wherein at least said first radiation component is emitted by at least one Light Emitting Diode (LED).

20. The method of claim 19, wherein said at least one LED has the spectral bandwidth of about 20-50 nm.

21. The method of claim 16, wherein said measurable relation is determined as a parametric slope PS:

22. The method of claim 16, wherein said analyzing of the relation between the detected radiation responses comprises comparing said relation to pre-determined calibration data, and extracting the value of said analyte concentration.

23. The method of claim 16, wherein said measurable relation is in the form of a quotient of time derivatives of the logarithms of said at least two radiation responses.

24. The method of claim 22, wherein said pre-determined calibration data is obtained by measuring and analyzing the radiation responses for a plurality of subjects together with their respective analyte concentrations and generating the calibration data.

25. The method of claim 23, wherein said analyzing of the relation between the detected radiation responses comprises applying to said relation a linear-regression algorithm and extracting a desired value of said analyte concentration.

26. The method of claim 23, wherein said analyzing of the relation between the detected radiation responses comprises comparing said quotient to pre-determined calibration data, and extracting the value of said analyte concentration.

27. The method of claim 26, wherein said pre-determined calibration data is obtained by measuring and analyzing the radiation responses for a plurality of subjects together with their respective analyte concentrations and generating the calibration data.

28. A method for use in determination of a hematocrit concentration, the method comprising:

providing at least two sources of electromagnetic radiation operable in different spectral regions of a hematocrit absorption coefficient spectrum;

selecting an operating spectral bandwidth of at least one of said sources of radiation such that said spectral bandwidth lies within a first spectral region of the absorption coefficient spectrum where variation of an absorption coefficient, Δ

β

₁, per volume fraction of said hematocrit as a function of wavelength is higher than in other spectral regions of said absorption coefficient spectrum and such that said spectral bandwidth contains a plurality of wavelengths with radiation intensities that are in a fixed relation to each other during a measurement time;

irradiating a medium with said radiation from said at least two sources of electromagnetic radiation during a certain measurement time to thereby produce detectable radiation transmitted through and/or reflected from the medium at said different spectral regions,

measuring the intensity of the radiation transmitted through and/or reflected from the medium at said different spectral regions; and

deriving from said transmitted and/or reflected radiation intensity a measurable relation between the medium radiation responses to different wavelengths, and analyzing said relation to determine the hematocrit concentration.

29. A method for use in determination of the concentration of an analyte in a subject'"'"'s medium having a certain extinction coefficient spectrum, the method utilizing illumination of the medium with at least two different radiation components during a certain measurement time and detecting radiation responses of the medium to said at least two radiation components, the method comprising:

selecting said at least two radiation components such that a first radiation component has a first mean wavelength and a first spectral bandwidth and the second radiation component has a second mean wavelength and a second spectral bandwidth, where the spectral bandwidth of said first radiation component lies within a first spectral region of the extinction coefficient spectrum where variation of an extinction coefficient, Δ

β

₁, per volume fraction of the analyte as a function of wavelength is higher than in other spectral regions within said extinction coefficient spectrum, and the spectral bandwidth of the second radiation component lies within a second spectral region where variation of an extinction coefficient, Δ

β

₂, per volume fraction of the analyte as a function of wavelength is smaller than in other spectral regions within said extinction coefficient spectrum, and at least said first radiation component contains a plurality of wavelengths with radiation intensity being in a fixed relation to each other during the certain measurement time, the plurality of wavelengths including at least two wavelengths that are spaced apart from one another along the first spectral region, a relation between the detected radiation responses being indicative of the concentration of said analyte.

30. A system for use in measuring the concentration of an analyte in a subject'"'"'s medium having a certain extinction coefficient spectrum for said analyte, the system comprising a light source unit configured and operable to produce at least first and second radiation components selected such that said first radiation component has a first mean wavelength and a first spectral bandwidth and said second radiation component has a second mean wavelength and a second spectral bandwidth, where the spectral bandwidth of said first radiation component lies within a first spectral region of said extinction coefficient spectrum where variation of an extinction coefficient, Δ

β

₁, per volume fraction of the analyte across the spectral bandwidth of the first radiation component is higher than in other spectral regions within said extinction coefficient spectrum and said second spectral bandwidth lies within a second spectral region where variation of an extinction coefficient, Δ

β

₂ per volume fraction of the analyte across the spectral bandwidth of the second radiation component, is smaller than in other spectral regions, and said first bandwidth contains a plurality of wavelengths with radiation intensities that are in a fixed relation to each other during a measurement time,

a detector unit comprising one or more light detectors for collecting light from the medium and generating data indicative thereof, and

a control unit connectable to the light source unit and to the detector unit, and being configured for processing and analyzing said data indicative of the detected light to determine a measurable relation between the detected radiation responses, and analyze said relation to derive therefrom the analyte concentration.

31. The system of claim 30, wherein the spectral bandwidth of at least said second radiation component is selected such that the variability of the extinction coefficient of said analyte across this spectral bandwidth is minimum in absolute value.

32. The system of claim 30, wherein the mean wavelength of said at least two radiation components is within red-near infrared optical spectral regions.

33. The system of claim 30, wherein the mean wavelength of said at least two radiation components is within about 400 nm-2300 nm.

34. The system of claim 30, wherein said one or more light detectors are adapted to collect light of said at least two radiation components transmitted through and/or reflected from the illuminated medium.

35. The system of claim 30, wherein the control unit is preprogrammed to determine said measurable relation as a parametric slope PS:

36. The system of claim 30, wherein said control unit is preprogrammed to analyze the determined measurable relation between the detected radiation responses by applying to said determined measurable relation a linear-regression algorithm and extracting a desired value of said analyte concentration.

37. The system of claim 30, wherein the spectral bandwidth of at least said first radiation component is selected such that the variability of the extinction coefficient of said analyte across this spectral bandwidth is maximal in absolute value.

38. The system of claim 30, wherein the control unit is preprogrammed to determine said measurable relation as a quotient of time derivatives of logarithms of said at least two detected radiation responses.

39. The system of claim 30, wherein said control unit is preprogrammed to analyze the determined measurable relation between the detected radiation components by comparing said determined measurable relation to pre-determined calibration data and extracting the value of said analyte concentration.

40. The system of claim 30, wherein said light source unit comprises at least one light source producing at least one of said at least two radiation components having a relatively broad spectral bandwidth, and at least one other light source producing light of a relatively narrow spectral bandwidth.

41. The system of claim 37, wherein the spectral bandwidth of at least said second radiation component is selected such that the variability of the extinction, coefficient of said analyte across this spectral bandwidth is minimum in absolute value.

42. The system of claim 39, wherein said calibration data is indicative of detected radiation responses recorded for a plurality of subjects together with their respective analyte concentrations.

43. The system of claim 38, wherein said control unit is preprogrammed to analyze the determined measurable relation between the detected radiation responses by comparing said quotient to pre-determined calibration data, and extracting the value of said analyte concentration.

44. The system of claim 43, wherein said calibration data is indicative of detected radiation responses recorded for a plurality of subjects together with their respective analyte concentrations.

45. The system of claim 40, wherein said at least one light source is a Light Emitting Diode (LED), and said at least one other light source is a laser.

46. The system of claim 40, wherein said at least one light source and said at least one other light source are Light Emitting Diodes (LEDs).

47. The system of claim 45, wherein said LED has the spectral bandwidth of about 20-50 nm.

48. The system of claim 46, wherein said LEDs have the spectral bandwidth of about 20-50 nm.

49. A system for use in determination of the concentration of an analyte in a subject'"'"'s medium having a certain extinction coefficient spectrum, the system comprising a measurement unit and a control unit connectable to the measurement unit, the measurement unit comprising a light source unit and a light detector unit, the light source unit being selected to be operable to produce at least two radiation components such that a first radiation component has a first mean wavelength and a first spectral bandwidth and a second radiation component has a second mean wavelength and a second spectral bandwidth, where the spectral bandwidth of said first radiation component lies within a first spectral region of said extinction coefficient spectrum where variation of an extinction coefficient, Δ

β

₁ per volume fraction of the analyte across the spectral bandwidth of the first radiation component, is higher than in other spectral regions within said extinction coefficient spectrum and the spectral bandwidth of said second radiation component lies within a second spectral region of said extinction coefficient spectrum where variation of an extinction coefficient, Δ

β

₂ per volume fraction of the analyte across the spectral bandwidth of the second radiation component, is smaller than in other spectral regions within said extinction coefficient spectrum and said at least one radiation component containing a plurality of wavelengths with radiation intensity being in a fixed relation to each other during a measurement time, the light detector unit comprising one or more light detectors adapted for collecting the radiation components after being transmitted through and/or reflected from the illuminated subject'"'"'s medium and generating data indicative of the collected light components, the control unit being configured for analyzing said data to determine a measurable relation between the collected light components and analyze said relation to derive therefrom the analyte concentration.