Rapid non-invasive optical analysis using broad bandpass spectral processing

• US 6,028,311 A
• Filed: 08/21/1998
• Issued: 02/22/2000
• Est. Priority Date: 07/15/1992
• Status: Expired due to Fees

• Current Assignee: Optix LP
• Original Assignee: Optix LP
• Inventors: Guthermann, Howard E., Block, Myron J., Sodickson, Lester
• Primary Examiner(s): Westin, Edward P.
• Assistant Examiner(s): Hanig, Richard
• Application Number:
  US09/137,857
• Time in Patent Office: 550 Days
• Field of Search: 250/343, 250/344, 250/345, 250/341.1, 250/339.11, 356/405, 356/39, 600/310
• US Class Current: 250/343
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• 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: A61B 5/6826 Finger
• CPC Class Codes: A61B 5/6838 Clamps or clips
• CPC Class Codes: G01N 2021/3137 with selection of wavelengths after the sample
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B

Abstract

The present invention provides a generally applicable apparatus and method for achieving measurements of a constituent in a sample. This is achieved by employing a detection means having a plurality of detectors responsive to radiation in a selected region of the spectrum, e.g., the infrared. In most embodiments, at least two of the detectors provide broad wavelength bandpass. If narrow bandpass sources or detectors are used, the information generated is processed in a manner similar to broadband information. The broad bandpass response of the detectors can be contrasted with the approach of classical spectrophotometry, in which the spectral response of the detectors is designed to be as narrow as feasible, and substantially narrower than the spectral features of the constituent or constituents of interest. The data is processed such that the contributions of known background constituents and scattering is eliminated prior to further processing, thereby yielding a better result in high background situations. The use of intensity processing rather than absorbance processing also allows the method and apparatus to be used in a variety of non-ideal situations.

Claims

1. An apparatus for determining the concentration of a constituent of interest in a sample which has transmittance, emittance, or reflectance in a selected region of the spectrum comprising:

illumination means which generates a plurality of beams of illuminating radiation in a selected region of the spectrum;

coding means for placing an identifiable, distinct code on each of said plurality of beams of radiation;

means for individually limiting the wavelength of each of said plurality of beams such that each beam is limited in wavelength to a distinct portion of said selected region of said spectrum, whereby at least one of said beams covers a broadband spectral region;

transmission means for transmitting said coded beams to illuminate said sample;

detection means for detecting the intensity of radiation transmitted, emitted, or reflected by said sample, said detection means including at least one broad band detector and decoding means for identifying the code on each of said coded beams, said detection means generating output signals which are functions of the information carried by each coded beam; and

analysis means for converting said output signals into a measure of said concentration of said constituent of interest in said sample;

wherein said analysis means generates a response which is an analog of a location in an n-dimensional colorimetric space, where n is equal to, or less than, the number of beams used to illuminate said sample.

2. The apparatus of claim 1 wherein at least two of said beams comprise overlapping broadband beams.

3. The apparatus of claim 1 wherein at least two of said beams comprise non-overlapping broadband beams.

4. The apparatus of claim 1 wherein said illuminating radiation comprises infrared radiation between about 700-2500 nm.

5. The apparatus of claim 1 wherein said illumination means comprises a radiation source and beam splitters which splits radiation generated by said radiation source into said plurality of beams.

6. The apparatus of claim 1 wherein said illumination means comprises a plurality of separate radiation sources.

7. The apparatus of claim 1 wherein said analysis means comprises a neural network.

8. The apparatus of claim 1 wherein said means for limiting the wavelength comprises a plurality of broad bandpass filters, each of said filters having a spectral transmission substantially limited to a distinct portion of the spectrum of illuminating radiation.

9. The apparatus of claim 1 wherein said coding means individually temporally modulates the intensity of said beams.

10. The apparatus of claim 9 wherein said coding means comprises a chopper associated with each of said beams.

11. The apparatus of claim 1 wherein said sample comprises a portion of an animal body.

12. The apparatus of claim 11 where said animal body is a human body.

13. The apparatus of claim 12 wherein said constituent of interest is an analyte of clinical interest.

14. The apparatus of claim 13 wherein said analyte of clinical interest is selected from the group consisting of glucose, glucose indicating constituents, drugs of abuse, drugs of abuse indicating constituents, alcohol, proteins, lipoproteins, hemoglobin and its variants, cholesterol, and lipids.

15. The apparatus of claim 1 wherein apparatus is arranged such that said plurality of separate beams provide congruent illumination of said sample.

16. The apparatus of claim 15 further comprising a plurality of detectors in said detection means and beam splitter means to direct the radiation reflected, emitted, or transmitted from said sample to said detectors.

17. The apparatus of claim 1 wherein said transmission means comprises a plurality of optical fibers, one end of each of said optical fibers admitting radiation from one of said beams, the other ends of said optical fibers being randomly distributed in a fiber bundle so as to provide substantially uniform distribution of said beams and illumination of said sample.

18. The apparatus of claim 17 wherein said optical fibers are arranged to provide congruent illumination.

19. The apparatus of claim 18 comprising at least a first detection means and a second detection means, each of said detection means having a distinct set of detectors therein.

20. The apparatus of claim 19 wherein at least one of said first and second detection means is arranged to provide incongruent measurement.

21. The apparatus of claim 19 wherein said analysis means comprises means to compare output signals generated from data from each of said detection means to generate a response indicative of the concentration of said constituent of interest while rendering the interfering features of the backgrounds from each of said detection means to be less distinct than if only one detection means was used.

22. The apparatus of claim 19 wherein said first detection means and said second detection means are arranged to obtain radiation from different portions of said sample.

23. The apparatus of claim 19 wherein said first and second detection means are arranged to provide congruent sampling.

24. The apparatus of claim 1 wherein said analysis means is arranged such that the outputs from said detectors are combined before any additional mathematical processing occurs.

25. The apparatus of claim 24 wherein said analysis means provides mathematical processing of intensity rather than absorbance values.

26. The apparatus of claim 1 wherein said analysis means comprises means to eliminate responses generated from known background components prior to any additional mathematical processing.

27. The apparatus of claim 1 wherein said apparatus comprises interrogation means which collects outputs from said detectors for all illumination beams substantially simultaneously.

28. The apparatus of claim 27 wherein said interrogation means collects outputs from said detectors in a sufficiently rapid manner to observe a distinct arterial pulse wave form so as to allow differentiation of constituents of interest in arterial blood.

29. The apparatus of claim 1 wherein said detectors are located such that they obtain radiation from said sample only within restricted solid angles.

30. The apparatus of claim 1 wherein at least a portion of said illuminating radiation is directed through a reference material to an additional detector to generate reference values.

31. The apparatus of claim 1 wherein said decoding means comprises electrical narrow bandpass filters substantially centered about the temporal frequency of modulation.

32. The apparatus of claim 1 wherein at least one of said detectors is formed, at least in part, from a material selected from the group consisting of silicon photocells, lead selenide cells, indium gallium arsenide cells, germanium cells, and lead sulfide cells.

33. The apparatus of claim 1 wherein said detection means further comprises a separate black/white luminosity detector which is responsive to and overlaps said spectral response of all of said plurality of detectors.

34. A method for determining the concentration of a constituent of interest in a sample which has transmittance, emittance, or reflectance in a selected region of the spectrum comprising:

coding each of a plurality of beams of illuminating radiation by placing an identifiable, distinct code thereon;

individually optically filtering each of said plurality of beams such that each beam is limited to a distinct portion of said selected region of said spectrum;

transmitting said coded beams to illuminate said sample;

detecting the intensity of radiation transmitted, emitted, or reflected by said sample;

decoding the code on each of said coded beams to generate an output signal which is a function of the information carried by each coded beam;

generating a processing input signal which is responsive to selected aspects of the background of the detection system and the sample, and said constituent of interest utilizing the output signal generated from a coded beam from a broadband source, and

analyzing said output signals and said processing input signal with an analysis means to generate a measure of said concentration of said constituent of interest in said sample;

wherein said analysis means generates a response which is an analog of a location in an n-dimensional colorimetric space, where n is equal to, or less than, the number of beams used to illuminate said sample.

35. The methods of claim 34 wherein said illuminating radiation comprises infrared radiation between about 700-2500 nm.

36. The method of claim 34 wherein said illumination step comprises illuminating said sample with an apparatus having a radiation source and beam splitters which split radiation generated by said radiation source into said plurality of beams.

37. The method of claim 34 wherein said illumination step comprises illuminating said sample with beams generated from a plurality of separate radiation sources.

38. The method of claim 34 wherein said analysis is carried out, at least in part, by a neural network.

39. The method of claim 34 wherein said optical filtering is carried out, at least in part, by a plurality of broad bandpass filters, each of said filters having a spectral transmission substantially limited to a distinct portion of the spectrum of illuminating radiation.

40. The method of claim 34 wherein said coding step is provided by individually temporally modulating the intensity of said beams.

41. The method of claim 40 wherein said coding step comprises modulation using a chopper associated with each of said beams.

42. The method of claim 34 wherein said sample comprises a portion of an animal body.

43. The method of claim 42 where said animal body is a human body.

44. The method of claim 43 wherein said constituent of interest is an analyte of clinical interest.

45. The method of claim 44 wherein said analyte of clinical interest is selected from the group consisting of glucose, glucose indicating constituents, drugs of abuse, drugs of abuse indicating constituents, alcohol, proteins, lipoproteins, hemoglobin and its variants, cholesterol, and lipids.

46. The method of claim 34 wherein said plurality of separate beams provide congruent illumination of said sample.

47. The method of claim 46 further comprising the step of directing the radiation reflected, emitted, or transmitted from said sample to a plurality of detectors in a detection means by a beam splitter.

48. The method of claim 34 wherein said beams are transmitted to said sample by a plurality of optical fibers, one end of each of said optical fibers admitting radiation from one of said beams, the other ends of said optical fibers being randomly distributed in a fiber bundle so as to provide substantially uniform distribution of said beams and illumination of said sample.

49. The method of claim 48 wherein said optical fibers are arranged to provide congruent illumination.

50. The method of claim 34 wherein said detecting step is carried out using at least a first detection means and a second detection means, each of said detection means having a distinct set of detectors therein.

51. The method of claim 50 wherein at least one of said first and second detection means is arranged to provide measurements that are not congruent measurements.

52. The method of claim 50 wherein said analysis step comprises comparing data generated from each of said detection means to generate information indicative of the concentration of said constituent of interest while rendering the interfering features of the backgrounds from each of said detection means to be less distinct than if a single detection means is used.

53. The method of claim 50 wherein said at least two distinct portions of said sample are illuminated and radiation therefrom is detected, said first detection means and said second detection means being arranged to obtain radiation from different portions of said sample.

54. The method of claim 50 wherein congruent sampling is achieved by geometric arrangement of said first and second detection means.

55. The method of claim 34 wherein said analysis step is carried out such that the data generated in said detection step is combined before any additional mathematical processing occurs.

56. The method of claim 55 wherein said analysis step acts by mathematical processing of intensity rather than absorbance values.

57. The method of claim 55 wherein said analysis step is used to eliminate data generated from known background components prior to any additional mathematical processing.

58. The method of claim 42 wherein said detection step comprises interrogating a detection means in a manner which is sufficiently rapid that the output signals from said detection means are collected substantially simultaneously for all illuminating beams.

59. The method of claim 58 wherein said interrogation step is carried out in a sufficiently rapid manner to observe a distinct arterial pulse wave form so as to allow differentiation of constituents of interest in arterial blood.

60. The method of claim 34 wherein said detecting step is carried out such that radiation is obtained from said sample only within a restricted solid angle.

61. The method of claim 34 wherein at least a portion of said illuminating radiation is directed through a reference material to a detector to generate reference values which can be used to correct for color constancy.

62. The method of claim 40 wherein said transmitting step includes transmitting said coded beam at a predetermined frequency and said decoding is achieved, at least in part, using electrical narrow bandpass filters substantially centered about said frequency.

63. The method of claim 34 wherein at least two of said beams have overlapping spectral characteristics.

64. The method of claim 34 wherein the outputs generated from a said broadband beam forms at least a part of said processing input signal.

65. A method for determining the concentration of a constituent of interest in a sample which has transmittance, emittance, or reflectance in a selected region of the spectrum comprising:

coding each of a plurality of beams of illuminating radiation by placing an identifiable, distinct code thereon;

individually optically filtering each of said plurality of beams such that each beam is limited to a distinct portion of said selected region of said spectrum;

transmitting said coded beams to illuminate said sample;

detecting the intensity of radiation transmitted, emitted, or reflected by said sample;

decoding the code on each of said coded beams to generate an output signal which is a function of the information carried by each coded beam;

generating a processing input signal which is responsive to selected aspects of the background of the detection system and the sample, and said constituent of interest utilizing the output signal generated by combining the output signals generated from coded beams from some of said detectors to simulate broadband detection, and

analyzing said output signals and said processing input signal with an analysis means to generate a measure of said concentration of said constituent of interest in said sample;

wherein said analysis means generates a response which is an analog of a location in an n-dimensional colorimetric space, where n is equal to, or less than, the number of beams used to illuminate said sample.