Non-invasive analysis system

• US 7,353,055 B2
• Filed: 06/17/2004
• Issued: 04/01/2008
• Est. Priority Date: 06/18/2003
• Status: Active Grant

• Current Assignee: Compact Imaging, Inc.
• Original Assignee: Josh N. Hogan
• Inventors: Hogan, Josh N.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US10/870,121
• Publication Number:
  US 20040260158A1
• Time in Patent Office: 1,384 Days
• Field of Search: 600/310, 600/316, 600/473, 600/476, 600/322, 356/450, 356/451, 356/456, 356/477, 356/479
• US Class Current: 600/316
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• 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

Abstract

A non-invasive analysis system suitable for measuring blood glucose concentration includes a broadband set of coherent beams, with relatively low divergence angle, optical source. It further includes an optical processing system which provides a probe and a reference beam, applies the probe beam to the target to be analyzed, recombines the beams interferometrically and varies the relative phase relationships of the two beams. It further includes control and processing systems.

Claims

1. A method for non-invasive measurement of an analyte in a target comprising:

generating a first repetitive discrete coherent optical signal wherein the first repetitive discrete coherent optical signal is generated by a first mode-locked laser;

applying at least part of said optical signal to the target to be analyzed, a portion of which will be scattered by the target;

capturing at least part of said optical signal scattered by the target;

generating a second repetitive discrete coherent optical signal wherein the second repetitive discrete coherent optical signal is a reference optical signal generated by a second mode-locked laser;

combining the captured scattered optical signal with said reference optical signal;

modifying the temporal coherence phase relationship between the captured scattered optical signal and said reference optical signal;

detecting an interference signal between the captured scattered optical signal and said reference optical signal;

analyzing the detected interference signal at multiple temporal relationships; and

determining the analyte measurement.

2. The method of claim 1, wherein the first mode-locked laser is a mode-locked semiconductor laser.

3. The method of claim 1, wherein the first mode-locked laser is electronically pumped.

4. The method of claim 1, wherein the first mode-locked laser is optically pumped by a semiconductor laser diode.

5. The method of claim 1, wherein the first mode-locked laser is a Cr:

LiSAF laser.

6. The method of claim 1, wherein at least a part of the generated optical signal is focused in the target to be analyzed by means of a lens with a long Rayleigh focus range.

7. The method of claim 6, wherein the Rayleigh range is of the order of one or more millimeters.

8. The method of claim 1, wherein part of the generated optical signal is scattered by discontinuities in the target.

9. The method of claim 8, wherein the discontinuities in the target are caused by changes of refractive index.

10. The method of claim 1, wherein the captured scattered signal is captured by the focusing lens.

11. The method of claim 1, wherein the captured scattered signal is separated from the first generated optical signal by means of a polarization separator.

12. The method of claim 1, wherein the second mode locked laser has a mode locking frequency offset from the first mode locked laser.

13. The method of claim 1, wherein the second mode locked laser has substantially the same wavelength range and substantially the same mode locking frequency as the first mode locked laser.

14. The method of claim 1, wherein the second mode locked laser has wavelength values offset from the wavelength values of the first mode locked laser by an offset that is substantially the same for all corresponding wavelengths.

15. The method of claim 1, wherein the coherence phase of the second mode locked laser is phase offset from the coherence phase of the first mode locked laser.

16. The method of claim 1, wherein the temporal relationship between the captured scattered signal and the reference optical signal is modified by modifying the coherence phase offset between the first and second mode locked lasers.

17. The method of claim 1, wherein the temporal relationship between the captured scattered signal and the reference optical signal is modified by means of the frequency offset between the first and second mode locked lasers.

18. The method of claim 1, wherein the temporal relationship between the captured scattered signal and the reference optical signal is modified by modifying the relative optical path difference between the captured scattered and reference optical signals.

19. The method of claim 1, wherein the captured scattered signal and the reference optical signal are combined interferometrically.

20. The method of claim 1, wherein the interference signal between the captured scattered and reference optical signals is detected by means of an opto-electronic detector.

21. The method of claim 1, wherein the interference signal between the captured scattered and reference optical signals is detected differentially by means of two opto-electronic detectors.

22. The method of claim 1, wherein the interference signals are detected by means of at least one opto-electronic detector at multiple temporal relationships between the captured scattered and reference optical signals.

23. The method of claim 1, wherein the detected signals are combined with electronic signals aligned with the coherence phase of the reference optical signal.

24. The method of claim 1, wherein the detected signals are analyzed by means of combining information from detected signals at at least two temporal relationships between the captured scattered and reference optical signals.

25. The method of claim 24, wherein the detected signals are analyzed to determine the detected signals as a function of the temporal relationships between the captured scattered and reference optical signals.

26. The method of claim 25, wherein the detected signals as a function of the temporal relationships between the captured scattered and reference optical signals are analyzed by an electronic processing system to determine an analyte characteristic within the target.

27. The method of claim 1, wherein a control system coordinates the temporal relationships between the captured scattered and reference optical signals, electronic signals aligned with the coherence phase of the reference optical signal, the detected signals and the processing system.

28. The method of claim 1, wherein the control system stores control parameters in electronic memory.

29. The method of claim 1, wherein the control system stores processed information in electronic memory.

30. The method of claim 1, wherein the analyte is glucose.

31. The method of claim 1, wherein the target is human tissue.

32. The method of claim 1, wherein the measurement is made continuously.

33. A system for non-invasive measurement of a characteristic of a target comprising:

a first mode locked laser operable to generate a first repetitive discrete coherent optical signal;

a lens operable to apply at least part of said optical signal to the target to be analyzed, a portion of which will be scattered by the target and to capture at least part of said optical signal scattered by the target;

a second mode locked laser operable to generate a second repetitive discrete coherent optical signal wherein the second repetitive discrete coherent optical signal is a reference optical signal;

a beam splitter operable to combine the captured scattered optical signal with said reference optical signal;

an electronic module operable to modify the temporal coherence phase relationship between the captured scattered optical signal and said reference optical signal;

a detector operable to detect an interference signal between the captured scattered signal and said reference optical signal;

an electronic processing module operable to analyze the detected interference signal at multiple temporal relationships and operable to determine the measurement of the characteristic.

34. An apparatus for non-invasively measuring of an analyte in a target comprising:

means for generating a first repetitive discrete coherent optical signal wherein the first repetitive discrete coherent optical signal is generated by a first mode locked laser;

means for applying at least part of said optical signal to the target to be analyzed, a portion of which will be scattered by the target;

means for capturing at least part of said optical signal scattered by the target;

means for generating a second repetitive discrete coherent optical signal wherein the second repetitive discrete coherent optical signal is a reference optical signal generated by a second mode locked laser;

means for combining the captured scattered optical signal with said reference optical signal;

means for modifying the temporal coherence phase relationship between the captured scattered optical signal and said reference optical signal;

means for detecting an interference signal between the captured scattered optical signal and said reference optical signal;

means for analyzing the detected interference signal at multiple temporal relationships; and

means for determining the analyte measurement.

35. The apparatus of claim 34, wherein the first mode locked laser is a mode locked semiconductor laser.

36. The apparatus of claim 34, wherein the first mode-locked laser is electronically pumped.

37. The apparatus of claim 34, wherein the first mode-locked laser is optically pumped by a semiconductor laser diode.

38. The apparatus of claim 34, wherein the first mode locked laser is a Cr:

LiSAF laser.

39. The apparatus of claim 34, wherein at least a part of the generated optical signal is focused in the target to be analyzed by means of a lens with a long Rayleigh focus range.

40. The apparatus of claim 39, wherein the Rayleigh range is of the order of one or more millimeters.

41. The apparatus of claim 34, wherein part of the generated optical signal is scattered by discontinuities in the target.

42. The apparatus of claim 41, wherein the discontinuities in the target are caused by changes of refractive index.

43. The apparatus of claim 34, wherein the captured scattered signal is captured by the focusing lens.

44. The apparatus of claim 34, wherein the captured scattered signal is separated from the first generated optical signal by means of a polarization separator.

45. The apparatus of claim 34, wherein the second mode locked laser has a mode locking frequency offset from the first mode locked laser.

46. The apparatus of claim 34, wherein the second mode locked laser has substantially the same wavelength range and substantially the same mode locking frequency as the first mode locked laser.

47. The apparatus of claim 34, wherein the second mode locked laser has wavelength values offset from the wavelength values of the first mode locked laser by an offset that is substantially the same for all corresponding wavelengths.

48. The apparatus of claim 34, wherein the coherence phase of the second mode locked laser may be phase offset from the coherence phase of the first mode locked laser.

49. The apparatus of claim 34, wherein the temporal relationship between the captured scattered signal and the reference optical signal is modified by modifying the coherence phase offset between the first and second mode locked lasers.

50. The apparatus of claim 34, wherein the temporal relationship between the captured scattered signal and the reference optical signal is modified by means of the frequency offset between the first and second mode locked lasers.

51. The apparatus of claim 34, wherein the temporal relationship between the captured scattered signal and the reference optical signal is modified by modifying the relative optical path difference between the captured scattered and reference optical signals.

52. The apparatus of claim 34, wherein the captured scattered signal and the reference optical signal are combined interferometrically.

53. The apparatus of claim 34, wherein the interference signal between the captured scattered and reference optical signals is detected by means of an opto-electronic detector.

54. The apparatus of claim 34, wherein the interference signal between the captured scattered and reference optical signals is detected differentially by means of two opto-electronic detectors.

55. The apparatus of claim 34, wherein the interference signals are detected by means of at least one opto-electronic detector at multiple temporal relationships between the captured scattered and reference optical signals.

56. The apparatus of claim 34, wherein the detected signals are combined with electronic signals aligned with the coherence phase of the reference optical signal.

57. The apparatus of claim 34, wherein the detected signals are analyzed by means of combining information from detected signals at least two temporal relationships between the captured scattered and reference optical signals.

58. The apparatus of claim 57, wherein the detected signals are analyzed to determine the detected signals as a function of the temporal relationships between the captured scattered and reference optical signals.

59. The apparatus of claim 58, wherein the detected signals as a function of the temporal relationships between the captured scattered and reference optical signals are analyzed by an electronic processing system to determine an analyte characteristic within the target.

60. The apparatus of claim 34, wherein a control system coordinates the temporal relationships between the captured scattered and reference optical signals, electronic signals aligned with the coherence phase of the reference optical signal, the detected signals and the processing system.

61. The apparatus of claim 34, wherein the control system stores control parameters in electronic memory.

62. The apparatus of claim 34, wherein the control system stores processed information in electronic memory.

63. The apparatus of claim 34, wherein the analyte is glucose.

64. The apparatus of claim 34, wherein the target is human tissue.

65. The apparatus of claim 34, wherein the measurement is made continuously.