Non-invasive analysis system

• US 20040260158A1
• Filed: 06/17/2004
• Published: 12/23/2004
• Est. Priority Date: 06/18/2003
• Status: Active Grant

• Current Assignee: Compact Imaging, Inc.
• Original Assignee: Josh N. Hogan
• Inventors: Hogan, Josh N.
• Granted Patent: US 7,353,055 B2
• Time in Patent Office: Days
• 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 at least one repetitive discrete coherent optical signal;

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;

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

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

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

analyzing the detected interference signal at multiple temporal relationships; and

determining the analyte measurement.

2. The method of claim 1, wherein the repetitive discrete coherent optical signal is generated by a first mode-locked laser.

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

4. The method of claim 2, wherein the laser is electronically pumped.

5. The method of claim 2, wherein the laser is optically pumped by a semiconductor laser diode.

6. The method of claim 2, wherein the mode-locked laser is a Cr:

LiSAF laser.

7. The method of claim 2, wherein mode locking is achieved electronically.

8. The method of claim 2, wherein mode locking is achieved passively.

9. The method of claim 8, wherein passive mode locking is achieved by means of a Kerr lens.

10. The method of claim 8, wherein passive mode locking is achieved by means of a semiconductor saturable absorber mirror.

11. 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.

12. The method of claim 11, wherein the Rayleigh range is of the order of one or more millimeters.

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

14. The method of claim 13, wherein the discontinuities in the target are caused by changes of refractive index.

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

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

17. The method of claim 1, wherein the captured scattered signal is combined with a reference optical signal generated by a second mode-locked laser.

18. The method of claim 17, wherein the second mode locked laser has a mode locking frequency offset from the first mode locked laser.

19. The method of claim 17, wherein the second mode locked laser has the same wavelength range and mode locking frequency as the first mode locked laser.

20. The method of claim 17, wherein the second mode locked laser has substantially the same wavelength values as the first mode locked laser.

21. The method of claim 17, 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.

22. The method of claim 17, wherein the coherence phase of the second mode locked laser may be phase offset from the coherence phase of the first mode locked laser.

23. The method of claim 1, wherein the captured scattered signal is combined with a reference optical signal which is a part of the first generated optical signal generated by the first mode locked laser.

24. 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.

25. 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.

26. 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.

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

28. 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.

29. 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.

30. 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.

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

32. The method of claim 1, 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.

33. The method of claim 32, 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.

34. The method of claim 33, 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.

35. 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.

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

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

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

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

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

41. A system for non-invasive measurement of target characteristics comprising:

generating at least one repetitive discrete coherent optical signal;

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;

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

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

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

analyzing the detected interference signal at multiple temporal relationships; and

determining the measurement of the characteristic.

42. A apparatus for non-invasively measuring of an analyte in a target comprising:

means for generating at least one repetitive discrete coherent optical signal;

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

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

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

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

means for determining the analyte measurement.

43. The apparatus of claim 42, wherein the repetitive discrete coherent optical signal is generated by a first mode locked laser.

44. The apparatus of claim 43, wherein the mode locked laser is a mode locked semiconductor laser.

45. The apparatus of claim 43, wherein the laser is electronically pumped.

46. The apparatus of claim 43, wherein the laser is optically pumped by a semiconductor laser diode.

47. The apparatus of claim 43, wherein the mode locked laser is a Cr:

LiSAF laser.

48. The apparatus of claim 43, wherein mode locking is achieved electronically.

49. The apparatus of claim 43, wherein mode locking is achieved passively.

50. The apparatus of claim 49, wherein passive mode locking is achieved by means of a Kerr lens.

51. The apparatus of claim 49, wherein passive mode locking is achieved by means of a semiconductor saturable absorber mirror.

52. The apparatus of claim 42, 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.

53. The apparatus of claim 52, wherein the Rayleigh range is of the order of one or more millimeters.

54. The apparatus of claim 42, wherein part of the generated optical signal is scattered by discontinuities in the target.

55. The apparatus of claim 54, wherein the discontinuities in the target are caused by changes of refractive index.

56. The apparatus of claim 42, wherein the captured scattered signal is captured by the focusing lens.

57. The apparatus of claim 42, wherein the captured scattered signal is separated from the first generated optical signal by means of a polarization separator.

58. The apparatus of claim 42, wherein the captured scattered signal is combined with a reference optical signal generated by a second mode locked laser.

59. The apparatus of claim 58, wherein the second mode locked laser has a mode locking frequency offset from the first mode locked laser.

60. The apparatus of claim 58, wherein the second mode locked laser has the same wavelength range and mode locking frequency as the first mode locked laser.

61. The apparatus of claim 58, wherein the second mode locked laser has substantially the same wavelength values as the first mode locked laser.

62. The apparatus of claim 58, 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.

63. The apparatus of claim 58, wherein the coherence phase of the second mode locked laser may be phase offset from the coherence phase of the first mode locked laser.

64. The apparatus of claim 42, wherein the captured scattered signal is combined with a reference optical signal which is a part of the first generated optical signal generated by the first mode locked laser.

65. The apparatus of claim 42, 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.

66. The apparatus of claim 42, 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.

67. The apparatus of claim 42, 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.

68. The apparatus of claim 42, wherein the captured scattered signal and the reference optical signal are combined interferometrically.

69. The apparatus of claim 42, wherein the interference signal between the captured scattered and reference optical signals is detected by means of an opto-electronic detector.

70. The apparatus of claim 42, wherein the interference signal between the captured scattered and reference optical signals is detected differentially by means of two opto-electronic detectors.

71. The apparatus of claim 42, 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.

72. The apparatus of claim 42, wherein the detected signals are combined with electronic signals aligned with the coherence phase of the reference optical signal.

73. The apparatus of claim 42, 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.

74. The apparatus of claim 73, 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.

75. The apparatus of claim 74, 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.

76. The apparatus of claim 42, 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.

77. The apparatus of claim 42, wherein the control system stores control parameters in electronic memory.

78. The apparatus of claim 42, wherein the control system stores processed information in electronic memory.

79. The apparatus of claim 42, wherein the analyte is glucose.

80. The apparatus of claim 42, wherein the target is human tissue.

81. The apparatus of claim 42, wherein the measurement is made continuously.