Method and device for measuring concentration of glucose or other substances in blood

• US 6,804,002 B2
• Filed: 12/11/2002
• Issued: 10/12/2004
• Est. Priority Date: 06/11/2000
• Status: Expired due to Term

• Current Assignee: OrSense Ltd.
• Original Assignee: OrSense Ltd.
• Inventors: Vinokur, Mark, Fine, Ilya, Fikhte, Boris
• Primary Examiner(s): Statira, Michael P.
• Application Number:
  US10/297,839
• Publication Number:
  US 20030137650A1
• Time in Patent Office: 671 Days
• Field of Search: 356/39-40, 356/364-370, 600/322-326, 369/364, 369/366, 369/368, 128/664-666
• US Class Current: 356/364
• CPC Class Codes: A61B 5/0053 by applying pressure, e.g. compression, indentation, palpation, grasping, gauging
• CPC Class Codes: A61B 5/14558 by polarisation
• CPC Class Codes: A61B 5/6826 Finger
• CPC Class Codes: A61B 5/6838 Clamps or clips
• CPC Class Codes: G01N 21/21 Polarisation-affecting properties G01N21/19 takes precedence

Abstract

A method and device for optical measurements are presented for determining the concentration of a substance in patient'"'"'s blood. Optical measurement sessions are applied to a measurement location in a blood containing medium during certain time period. The optical measurements include illumination of the measurement location with incident light of at least one selected wavelength, detection, at each measurement session, of at least two light responses of the medium characterized by at least two different polarization states of detected light, respectively, and generation of data representative thereof. Measured data so obtained is in the form of at least two time variations of the light responses of the medium characterized by different polarization states of detected light, respectively, a relation between the time variations being indicative of the concentration of the substance in blood.

Claims

1. A method of optical measurements for use in determining the concentration of a substance in a patient'"'"'s blood, the method comprising

creating a state of blood flow cessation at the measurement location by applying pressure to a location on the blood containing medium upstream of said measurement location with respect to the blood flow direction, and maintaining said state for a certain cessation time, during a certain time period including said certain cessation time, performing optical measurement sessions on the measurement location by illuminating the measurement location with incident light of at least one selected wavelength, detecting, at each measurement session, at least two light responses of the medium characterized by at least two different polarization states of detected light, respectively, and generating data representative thereof;

and

obtaining measured data in the form of at least two time variations of the light responses of the medium, a relation between the time variations of the light responses being indicative of the concentration of the substance in blood.

3. The method according to claim 1, wherein said substance is optically active or scattering affecting substance.

2. A method of non-invasive optical measurements for use in determining the concentration of a substance in a patient'"'"'s blood, the method comprising:

creating a state of blood flow cessation at a measurement location in the patient'"'"'s blood perfused fleshy medium by applying over-systolic pressure to the medium at a location upstream of said measurement location with respect to the blood flow direction, and maintaining said state for a certain cessation time being insufficient for irreversible changes in the fleshy medium;

during a certain time period including said certain cessation time, performing optical measurement sessions at the measurement location by illuminating the measurement location with incident light of at least one selected wavelength, detecting, at each measurement session, at least two light responses of the medium characterized by at least two different polarization states of detected light, respectively, and generating data representative thereof; and

obtaining measured data in the form of at least two time variations of the light responses of the medium, a relation between the time variations being indicative of the concentration of the substance in blood.

4. A method of optical measurements for determining the concentration of a substance in a patient'"'"'s blood, the method comprising the steps of:

creating a state of blood flow cessation within a measurement location in a blood flow containing medium, and maintaining said state during a certain cessation time;

performing optical measurement sessions within a time period including said certain cessation time, the optical measurements including illumination of the measurement location with incident light of at least one selected wavelength, detection, at each measurement session, of at least two light responses of the medium characterized by at least two different polarization states of detected light, respectively, and generation of data representative thereof;

obtaining measured data in the form of at least two time variations of the light responses of the medium, a relation between the time variations being indicative of the concentration of the substance in blood.

5. The method according to claim 4, wherein said substance is optically active or scattering affecting substance.

6. The method according to claim 5, wherein said substance is glucose.

7. The method according to claim 5, wherein said at least one selected wavelength is in the range of visual or near infrared spectra.

8. The method according to claim 4, wherein the measurements are performed in vitro.

9. The method according to claim 4, wherein the measurements are performed in vivo.

10. The method according to claim 4, wherein said relation between the time variations is a parametric slope of a curve, which is in the form of one light response as the function of the other.

11. The method according to claim 4, wherein said relation between the time variations is degree of depolarization calculated as a ratio between the difference of light responses'"'"' intensities and their sum.

12. The method according to claim 4, wherein the optical measurements during each of the measurement sessions comprises:

illuminating the medium with at least two incident beams having different polarization states, such as to produce at least two output light beams coming from the illuminated medium; and

directing the output light beams towards a detector unit through an analyzer whose plane of preferred polarization is specifically oriented with respect to that of the incident beams.

13. The method according to claim 4, wherein the optical measurements during each of the measurement sessions comprises:

illuminating the medium with a beam of incident light having a certain state of polarization, such as to produce an output light beam coming from the illuminated medium; and

directing the output light beam towards two detector units, such that only one light component of the output light beam is directed towards a corresponding one of the detector units through an analyzer whose plane of preferred polarization is specifically oriented with respect to that of the incident beam, while the other light component of the output light beam is directly detected by the other detector unit.

14. The method according to claim 4, wherein the optical measurements during each of the measurement sessions comprises:

illuminating the medium with a beam of incident light having a certain state of polarization, so as to produce an output light beam coming from the illuminated medium;

directing the output light beam towards two detector units through two analyzer units, respectively, the analyzer units having planes of preferred polarization oriented differently to each other and to that of the incident beam.

15. A method of optical measurements for non-invasively determining the concentration of a substance in a patient'"'"'s blood, the method comprising the steps of:

applying over-systolic pressure to a location on the patient'"'"'s blood perfused fleshy medium, thereby creating a state of blood flow cessation within a measurement location downstream of the location of application of pressure, and maintaining said state during a certain cessation time;

performing optical measurement sessions within a time period including said certain cessation time, the optical measurements including illumination of the measurement location with incident light of at least one selected wavelength, detection, at each measurement session, of at least two light responses of the medium characterized by at least two different polarization states of detected light, respectively, and generation of data representative thereof;

obtaining measured data in the form of at least two time variations of the light responses of the medium, a relation between the time variations being indicative of the concentration of the substance in blood.

16. A method for determining the concentration of a scattering affecting or optically active substance in a patient'"'"'s blood, the method comprising the steps of:

(i) providing reference data indicative of a preset measurable parameter as a function of values of said concentration;

(ii) creating a state of blood flow cessation within a measurement location in a blood flow containing medium, and maintaining said state during a certain cessation time;

(iii) performing optical measurement sessions within a time period including said certain cessation time, the optical measurements including illumination the measurement location with incident light of at least one selected wavelength, detection, at each measurement session, of at least two light responses of the medium characterized by at least two different polarization states of detected light, respectively, and generation of measured data representative thereof;

(iv) utilizing the measured data for obtaining measurement results in the form of at least two kinetic curves of the light responses of the medium as functions of time corresponding to the different polarization states of the detected light;

(v) analyzing said at least two kinetic curves for calculating said certain measurable parameter indicative of relation between them; and

(vi) utilizing the calculated value and said reference data for determining the concentration of the substance in the patient'"'"'s blood.

17. The method according to claim 16, wherein said substance is glucose.

18. The method according to claim 16, wherein said at least one selected wavelength is in the range of visual or near infrared spectra.

19. The method according to claim 16, wherein said reference data comprises a calibration curve obtained by applying steps (b) to (e) to blood containing media with different known values of the concentration of said substance.

20. The method according to claim 16, wherein the measurements are performed in vitro.

21. The method according to claim 16, wherein the measurements are performed in vivo.

22. The method according to claim 21, wherein said measurement location is located at the patient'"'"'s finger.

23. The method according to claim 16, wherein said certain measurable parameter is a parametric slope of a curve, which is in the form of one light response as the function of the other.

24. The method according to claim 16, wherein said certain measurable parameter is degree of depolarization calculated as a ratio between the difference of the light responses'"'"' intensities, and their sum.

25. The method according to claim 16, wherein, in step (c), the optical measurements during each of the measurement sessions comprises:

illuminating the medium with at least two incident beams having different polarization states, such as to produce at least two output light beams coming from the illuminated medium;

directing the output light beams towards a detector unit through an analyzer whose plane of preferred polarization is specifically oriented with respect to that of the incident beams.

26. The method according to claim 16, wherein, step (c), the optical measurements during each of the measurement sessions comprises:

illuminating the medium with a beam of incident light having a certain state of polarization, such as to produce an output light beam coming from the illuminated medium;

directing the output light beam towards two detector units, such that only one light component of the output light beam is directed towards a corresponding one of the detector units through an analyzer whose plane of preferred polarization is specifically oriented with respect to that of the incident beam, while the other light component of the output light beam is directly detected by the other detector unit.

27. The method according to claim 16, wherein, in step (c), the optical measurements during each of the measurement sessions comprises:

illuminating the medium with a beam of incident light having a certain state of polarization, so as to produce an output light beam coming from the illuminated medium;

directing the output light beam towards two detector units through two analyzer units, respectively, the analyzer units having planes of preferred polarization oriented differently to each other and to that of the incident beam.

28. A method for non-invasively determining the concentration of a substance in a patient'"'"'s blood, the method comprising the steps of:

providing reference data indicative of a preset measurable parameter as a function of values of said concentration;

applying over-systolic pressure to a location of the patient'"'"'s blood perfused fleshy medium, thereby creating a state of blood flow cessation within a measurement location downstream of the location of application of pressure with respect to the blood flow direction, and maintaining said state of the blood flow cessation during a certain cessation time being insufficient for irreversible changes in the fleshy medium;

performing optical measurement sessions within a time period including said certain cessation time, the optical measurements including illumination of the measurement location with incident light of at least one selected wavelength, detection, at each measurement session, of at least two light responses of the medium characterized by at least two different polarization states of detected light, respectively, and generation of data representative thereof;

utilizing the measured data for obtaining measurement results in the form of at least two kinetic curves of the light responses of the medium as functions of time corresponding to the different polarization states of the detected light;

analyzing said at least two kinetic curves for calculating said certain parameter indicative of relation between them, and

utilizing the calculated value and said reference data for determining the concentration of the substance in the patient'"'"'s blood.

29. An optical measurement system for obtaining data indicative of the concentration of a scattering affecting or optically active substance in patient'"'"'s blood, the system comprising:

(a) a measurement device comprising a pressurizing assembly and a measuring unit, wherein the pressurizing assembly has a pressing member for wrapping a region on a blood flow containing medium that is operable for applying over-systolic pressure to said region so as to create a state of blood flow cessation at a measurement location in the medium, and the measuring unit is operable for performing optical measurement sessions at said measurement location, and comprises an illumination system for illuminating the measurement location with specifically polarized light of at least one selected wavelength during at least two measurement sessions, and a light collection/detection system for applying polarization filtering to light propagating from the measurement location, thereby enabling detecting, at each measurement session, at least two light responses of the medium characterized by the same wavelength and at least two different polarization states, respectively, and generating measured data representative thereof; and

(b) a control unit connectable to the measurement device for selectively operating said measuring unit and said pressurizing assembly, such that the state of blood flow cessation is maintained during a certain cessation time and the optical measurement sessions are performed during a time period within said certain cessation time, the control unit being responsive to said measured data to determine time variations of the light responses of the medium corresponding to said at least two different polarization states of the detected light, analyze the time variations for determining a preset parameter measured as a relation between the time variations, and being indicative of the time variation of depolarization of light caused by the scattering affecting or optically active substance in the medium.

30. The system according to claim 29, wherein

the illumination system comprises an illuminator operable for generating at least one beam of incident light of the selected wavelength, and a polarizer unit,

the light collection/detection system comprises at least one detector unit and at least one analyzer, a plane of preferred polarization of said at least one analyzer being specifically oriented with respect to that of the polarizer unit, said at least one detector unit detecting the light responses of the medium and generating the measured data indicative thereof.

31. The system according to claim 29, wherein said substance is glucose.

32. The system according to claim 29, wherein the measurement location is located at the patient'"'"'s finger.

33. The system according to claim 29, wherein the measurement location is located inside a flow cuvette through which the flow of patient'"'"'s blood sample is drawn.

34. The system according to claim 32, wherein said pressing member of the pressurizing assembly is a cuff for wrapping the patient'"'"'s finger, squeezing of the cuff being operated by a drive coupled to the control unit.

35. The system according to claim 29, wherein the pressurizing assembly comprises a peristaltic pump operated by a drive coupled to the control unit.

36. The system according to claim 30, wherein

said illuminator is operable to produce two beams of light, and said polarizer unit comprises at least one polarizer accommodated in optical path of one of said two beams, thereby producing two incident beams of different polarization state, respectively, and producing two output beams coming from the illuminated medium;

the collection/detection system comprises the single analyzer accommodated in optical path of the output light propagating towards the single detector unit.

37. The system according to claim 30, wherein

said illuminator is operable to produce two beams of light, and said polarizer unit comprises a polarizer accommodated in the optical path of each of said two beams, and a retarder accommodated in the optical path of each of said two beams and operable with different operational modes with respect to said two beams, the illuminator thereby producing two incident beams of different polarization states, respectively;

the collection/detection system comprises the single analyzer accommodated in optical path of the output light propagating towards the single detector unit.

38. The system according to claim 30, wherein

said illuminator is operable to generate a beams of light, and said polarizer unit comprises a polarizer accommodated in optical path of the generated beam propagating towards the medium, thereby producing output light coming from the illuminated medium;

the collection/detection system comprises two detector units for detecting two spatially separated light components of the output light, two analyzers being accommodated in optical path of said two light components, respectively, propagating towards the detection units, the analyzers having different orientation of planes of preferred polarization.

39. The system according to claim 29, wherein said preset measurable parameter is a parametric slope of a curve, which is in the form of one light response as the function of the other.

40. The system according to claim 29, wherein said preset measurable parameter is degree of depolarization calculated as a ratio between the difference of the light responses'"'"'intensities, and their sum.

41. The system according to claim 29, wherein

the control unit operates said pressurizing assembly, such that said cessation time during which the over-systolic pressure is applied is insufficient for irreversible changes in the fleshy medium.

42. The device according to claim 29, wherein said at least one selected wavelength is in the range of visual or near infrared spectra.

43. A measurement system for non-invasively determining the concentration of a substance in a patient'"'"'s blood, the system comprising:

a measurement device that comprises a pressurizing assembly operable to apply over-systolic pressure to a location on the patient'"'"'s blood perfused fleshy medium, so as to create a state of blood flow cessation at a measurement location in the medium located downstream of the location of application of pressure; and

comprises a measuring unit operable to perform optical measurement sessions to said measurement location, the measuring unit comprising an illumination system and a light collection/detection system which are operable so as to detect at least two light responses of the medium characterized by at least two different polarization states of detected light, respectively, and generate measured data representative thereof; and

a control unit connectable to the measurement device for selectively operating said measuring unit and said pressurizing assembly, such that the state of blood flow cessation is maintained during a certain cessation time being insufficient for irreversible changes in the fleshy medium, and the optical measurement sessions are performed within a time period including said cessation time, the control unit being responsive to said measured data to determine time variations of said at least two light responses of the medium corresponding to at least two different polarization states of the detected light, analyze the time variations for determining a preset parameter measured as a relation between the time variations, and determining the concentration of said substance using reference data indicative of the preset measurable parameter as a function of values of the substance concentration.

44. A measurement device for performing non-invasive optical measurements for determining the concentration of a substance in patient'"'"'s blood, the device comprising:

a pressurizing assembly operable to apply over-systolic pressure to a location on the patient'"'"'s blood perfused fleshy medium, so as to create a state of blood flow cessation at a measurement location in the medium located downstream of the location of application of pressure, and to maintain said state during a certain cessation time being insufficient for irreversible changes in the fleshy medium; and

a measuring unit operable to perform optical measurement sessions at said measurement location within a time period including said cessation time, the measuring unit comprising an illumination system and a light collection/detection system which are operable to detect, at each measurement session, at least two light responses of the medium characterized by at least two different polarization states of detected light, respectively, and generate measured data representative thereof, the measured data being indicative of time variations of said at least two light responses of the medium corresponding to at least two different polarization states of the detected light, a relation between said time variations being indicative of the concentration of said substance.

45. The device according to claim 44, wherein said substance is optically active or scattering affecting substance.

46. The device according to claim 45, wherein said substance is glucose.

47. The device according to claim 44, wherein said at least one selected wavelength is in the range of visual or near infrared spectra.

48. The device according to claim 44, wherein the pressurizing assembly comprises a cuff for wrapping a patient'"'"'s finger, and is operable for squeezing the cuff.

49. The device according to claim 44, wherein

said illumination system comprises an illuminator operable to produce two beams of light, and a polarizer unit that comprises at least one polarizer accommodated in optical path of one of said two beams, thereby producing two incident beams of different polarization state, respectively, and producing two output beams coming from the illuminated medium;

the light collection/detection system comprises a single analyzer accommodated in optical path of the output light propagating towards a single detector unit.

50. The device according to claim 44, wherein

said illumination system comprises an illuminator operable to produce two beams of light, and a polarizer unit hat comprises a polarizer accommodated, in the optical path of each of said two beams, and a retarder accommodated in the optical path of each of said two beams and operable with different operational modes with respect to said two beams, the illuminator thereby producing two incident beams of different polarization states, respectively;

the light collection/detection system comprises a single analyzer accommodated in optical path of the output light propagating towards a single detector unit.

51. The device according to claim 44, wherein

said illumination system comprises an illuminator operable to generate a beams of light, and a polarizer unit that comprises a polarizer accommodated in optical path of the generated beam propagating towards the medium, thereby producing output light coming from the illuminated medium;

the light collection/detection system comprises two detector units for detecting two spatially separated light components of the output light, two analyzers being accommodated in optical path of said two light components, respectively, propagating towards the detection units, the analyzers having different orientations of planes of preferred polarization.

52. The device according to claim 44, wherein said relation between the time variations is a parametric slope of a curve, which is in the form of one light response as the function of the other.

53. The device according to claim 44, wherein said relation between the time variations is degree of depolarization calculated as a ratio between the difference of light responses'"'"' intensities and their sum.