Rapid non-invasive optical analysis using broad bandpass spectral processing

• US 5,818,048 A
• Filed: 11/03/1994
• Issued: 10/06/1998
• 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): Tokar, Michael J.
• Assistant Examiner(s): HANIG, RICHARD E
• Application Number:
  US08/333,758
• Time in Patent Office: 1,433 Days
• Field of Search: 250/343, 250/339.01, 250/340, 250/341.1, 250/345, 356/405
• 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, emission or reflectance in a selected region of the spectrum comprising:

a radiation source which generates a spectrum of illuminating radiation for illuminating at least a portion of said sample;

detection means in the form of three or more detectors adapted to generate an output, each of said detectors having a spectral response in a portion of said spectrum of illuminating radiation emitted by said radiation source, at least one of said detectors having a broadband spectral response, at least one of said detectors further having an overlap in spectral response with another of said detectors; and

analysis means for analyzing said outputs from said detectors to generate a signal indicative of the concentration of said constituent of interest in said sample.

2. The apparatus of claim 1 wherein at least two of said three or more detectors comprise overlapping broadband detectors.

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

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

5. The apparatus of claim 4 wherein said analysis means generates an output which is an analog of a location in an n-dimensional colorimetric space, where n is equal to, or less than, the number of detectors in said detection means.

6. 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 three or more detectors.

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

8. The apparatus of claim 1 wherein at least one of said detectors comprises a filter which transmits or reflects a portion of the spectrum of illuminating radiation, said filter acting, at least in part, to generate the spectral response characteristics of said detector.

9. 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.

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

11. The apparatus of claim 10 where said animal body is a human body.

12. The apparatus of claim 11 wherein said constituent of interest is an analyte of clinical interest.

13. The apparatus of claim 12 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.

14. The apparatus of claim 1 wherein said detectors are located geometrically in said apparatus such that they congruently sample radiation reflected, emitted, or transmitted from said sample.

15. The apparatus of claim 14 further comprising beam splitter means to direct the radiation reflected or transmitted from said sample to said detectors.

16. The apparatus of claim 1 wherein said detection means comprises a fiber optic cable bundle containing a plurality of optical fibers which transmit radiation reflected or transmitted from said sample to said three or more detectors.

17. The apparatus of claim 16 wherein said optical fibers in said bundle have their ends distal from said detectors randomly distributed in said bundle so as to achieve substantially equivalent illumination for each detector from said sample.

18. The apparatus of claim 1 comprising at least a first detection means and a second detection means, each of said detection means having a distinct set of detectors therein.

19. The apparatus of claim 18 wherein at least one of said first and second detection means is arranged to provide incongruent measurement.

20. The apparatus of claim 18 wherein said analysis means comprises means to compare responses from each of said detection means to generate an information signal indicative of the concentration of said constituent of interest while rendering the interfering features of the background from each of said detection means to be less distinct than it is in the response from the individual detection means.

21. The apparatus of claim 18 wherein said first detection means and said second detection means are arranged to obtain radiation from different portions of said sample.

22. 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.

23. The apparatus of claim 22 wherein said analysis means provides mathematical processing of intensity rather than absorbance values.

24. 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.

25. The apparatus of claim 1 wherein said apparatus comprises interrogation means which collects outputs from said detectors substantially simultaneously.

26. The apparatus of claim 25 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, as opposed to venous blood or tissue.

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

28. 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.

29. The apparatus of claim 1 wherein said radiation source comprises at least two radiation sources.

30. The apparatus of claim 29 wherein said radiation sources are arranged to provide congruent illumination.

31. The apparatus of claim 29 wherein said radiation sources are arranged such that a fiber optic cable bundle containing a plurality of optical fibers can transmit radiation from said radiation sources to said sample.

32. The apparatus of claim 1 wherein at least a portion of said illuminating radiation is directed through a reference material to a detector on a time shared basis to generate reference values.

33. 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 the steps of:

illuminating at least a portion of said sample with a radiation source which generates a spectrum of illuminating radiation;

detecting radiation reflected, emitted, or transmitted by said sample with detection means in the form of three or more detectors adapted to generate an output, each of said detectors having a spectral response in a portion of said spectrum of illuminating radiation emitted by said radiation source;

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 from a broadband detector, or combining the outputs from some of said detectors to simulate broadband detection, at least one of said detectors further having an overlap in spectral response with another of said detectors; and

analyzing some of said outputs and said processing input signal with an analysis means which generates a response indicative of the concentration of said constituent of interest in said sample.

34. The method of claim 33 wherein said illuminating radiation comprises infrared radiation between about 700-2500 nm.

35. The method of claim 33 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 detectors in said detection means.

36. The method of claim 33 wherein said analysis step is carried out, at least in part, by a neural network.

37. The method of claim 33 further comprising the step of normalizing the intensity of all the radiation transmitted, emitted, or reflected from said sample without regard to wavelength by including in said detection means a black/white luminosity detector which is responsive to and overlaps said spectral response of all of said three or more detectors.

38. The method of claim 33 wherein at least one of said detectors comprises a filter which transmits or reflects a portion of the spectrum of illuminating radiation, said filter acting, at least in part, to generate the spectral response characteristics of said detector.

39. The method of claim 33 wherein at least one of said detectors is a broadband detector.

40. The method of claim 39 wherein at least two of said detectors have overlapping spectral characteristics.

41. The method of claim 39 wherein the outputs of at least said broadband detector forms an input to said processing input signal.

42. The method of claim 33 wherein at least one of said detectors is formed, at least in part, of a material selected from the group consisting of silicon photocells, lead selenide cells, indium gallium arsenide cells, germanium cells, and lead sulfide cells.

43. The method of claim 33 wherein said method is directed at determining the concentration in vivo of an analyte of clinical interest in a portion of a human body and said method is used for non-invasive testing.

44. The method of claim 33 wherein said method is directed at determining the concentration in vitro of an analyte of clinical interest from a human body and said method is used on a fluid or tissue sample removed from said body.

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, pharmaceuticals, alcohol, proteins, lipoproteins, hemoglobin and its variants, cholesterol, and lipids.

46. The method of claim 33 wherein said detectors are located geometrically relative to said sample such that they congruently sample radiation reflected, emitted, or transmitted from said sample.

47. The method of claim 46 wherein beam splitters are used to direct the radiation reflected, emitted, or transmitted from said sample to said detectors so as to achieve congruent sampling.

48. The method of claim 33 wherein said radiation reflected, emitted, or transmitted from said sample to said detectors is transmitted to said detection means by a fiber optic cable bundle containing a plurality of optical fibers.

49. The method of claim 48 wherein said optical fibers in said bundle have their ends distal from said detectors randomly distributed in said bundle so as to achieve substantially equivalent illumination to each detector from said sample.

50. The method of claim 33 comprising the step of generating distinct outputs from individual detectors in at least a first detection means and a second detection means, each of said detection means having a selected set of detectors therein.

51. The method of claim 50 comprising the step of comparing responses generated from data 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 only a single detection means was used.

52. The method of claim 51 wherein said first and second detection means obtain radiation transmitted, emitted or reflected from different portions of said sample.

53. The method of claim 50 wherein one of said first and second detectors means is arranged to provide incongruent measurement.

54. The method of claim 33 wherein said outputs and said processing input signals from said detectors are combined before any additional mathematical processing occurs.

55. The method of claim 54 wherein mathematical processing by said analysis means is carried out on intensity rather than absorbance values.

56. The method of claim 54 wherein the analyzing of said outputs and said processing input signals comprises eliminating responses generated from known background components prior to any additional mathematical processing.

57. The method of claim 33 wherein said outputs from each of said detectors are sampled by an interrogation device sufficiently rapidly so as to be substantially simultaneous.

58. The method of claim 57 wherein said interrogation device collects said 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.

59. The method of claim 33 wherein radiation from said sample is obtained only from within a restricted solid angle.

60. The method of claim 33 wherein at least a portion of said illuminating radiation is directed through a reference material to an additional detector to generate reference values.

61. The method of claim 33 wherein said illuminating radiation is generated by at least two radiation sources.

62. The method of claim 61 wherein said radiation sources are arranged to provide congruent illumination.

63. The method of claim 61 wherein said radiation sources transmit radiation to said sample through optical fiber bundles and the optical fibers in said bundle have their ends distal from said radiation sources randomly distributed in said bundle so as to achieve substantially equivalent illumination from each of said radiation sources to said sample.

64. The method of claim 33 wherein at least a portion of said illuminating radiation is directed through a reference material to a detector on a time share basis to generate reference values.