Low coherence interferometry utilizing magnitude

• US 7,327,463 B2
• Filed: 05/14/2004
• Issued: 02/05/2008
• Est. Priority Date: 05/14/2004
• Status: Expired due to Fees

• Current Assignee: Cardiolumen, Inc.
• Original Assignee: Medrikon Corporation
• Inventors: Alphonse, Gerard A.
• Primary Examiner(s): CONNOLLY, PATRICK J
• Application Number:
  US10/845,853
• Publication Number:
  US 20050254058A1
• Time in Patent Office: 1,362 Days
• Field of Search: 356/479, 356/497, 356/477
• US Class Current: 356/479
• 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 5/14558 by polarisation
• CPC Class Codes: G01B 2290/70 Using polarization in the interferometer
• CPC Class Codes: G01B 9/0201 using temporal phase variation
• CPC Class Codes: G01B 9/02014 by using pulsed light
• CPC Class Codes: G01B 9/02074 of the detector
• CPC Class Codes: G01B 9/0209 Low-coherence interferometers

Abstract

A method for determining a characteristic of an analyte in a biological sample, the method comprising: directing broadband light by means of a sensing light path at the biological sample, at a target depth defined by the sensing light path and a reference light path; receiving the broadband light reflected from the biological sample by means of the sensing light path; directing the broadband light by means of the reference light path at a fixed reflecting device; and receiving the broadband light reflected from the fixed reflecting device by means of the reference light path. The method also includes interfering the broadband light reflected from the biological sample and the broadband light reflected from the fixed reflecting device; varying an effective light path length of at least one of the reference light path and the sensing light path to define an other target depth; detecting the broadband light resulting from interference of the broadband light reflected from the biological sample and the broadband light reflected from the fixed reflecting device for each of the target depths, to provide an intensity measurement at each of the target depths; and determining the characteristic of the analyte in the biological sample from variations in the intensity measurements.

Claims

1. A method for determining a characteristic of an analyte in a biological sample, the method comprising:

directing broadband light by means of a sensing light path at the biological sample, at a target depth defined by said sensing light path and a reference light path;

receiving said broadband light reflected from the biological sample by means of said sensing light path;

directing said broadband light by means or said reference light path at a fixed reflecting device;

receiving said broadband light reflected from said fixed reflecting device by means of said reference light path;

modulating at about a distance of a center wavelength of said broadband light an effective light path length of at least one of said reference light path and said sensing light path with respect to said target depth;

detecting said broadband light resulting from said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate a signal indicative of an interference of said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, said signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said target depth;

wherein said effective light path length of at least one of said reference light path and said sensing light path is modulated such that said phase component of said signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said target depth;

changing said effective light path length of at least one of said reference light path and said sensing light path to define an other target depth, said other target depth is at a distance of about at least a coherence length of said broadband light from said target depth;

modulating at about a distance of the center wavelength of said broadband light said effective light path length of at least one of said reference light path and said sensing light path with respect to said other target depth;

detecting said broadband light resulting from said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate an other signal indicative of an interference of said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device for said other target depth, said other signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said other target depth;

wherein said effective light path length of at least one of said reference light path and said sensing light path is modulated such that said phase component of said other signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said other target depth;

determining the characteristic of the analyte in the biological sample from variations in said intensity measurements; and

diagnosing a human condition from the characteristic.

2. The method of claim 1 wherein said determining the characteristic of the analyte in the biological sample from variations in said intensity measurements comprises:

determining a scattering coefficient from said variations in said intensity measurements; and

determining the characteristic of the analyte in the biological sample from said scattering coefficient.

3. The method of claim 1 wherein said target depth is defined by said effective light path length of said reference light path and said effective light path length of said sensing light path.

4. The method of claim 3 wherein said other target depth is defined by said effective light path length of at least one of said reference light path and said sensing light path having been changed.

5. The method of claim 1 wherein at least one of said reference light path and said sensing light path comprises at least one of an optical fiber and a waveguide.

6. The method of claim 1 wherein at least one of said modulating employs at least one metallic electrodes disposed at an optical waveguide and an optical fiber wound on a piezoelectric drum forming at least a portion of at least one of said reference light path and said sensing light path.

7. The method of claim 1 further including calibrating at least one of said reference light path and said sensing light path by adjusting effective light path length of at least one of said reference light path and said sensing light path based on a sample exhibiting properties including at least one of known refractive index and scattering coefficient.

8. A system for determining a characteristic of an analyte in a biological sample, the system comprising:

a broadband light source for providing a broadband light;

a sensing light path receptive to said broadband light from said broadband light source, said sensing light path configured to direct said broadband light at the biological sample and to receive said broadband light reflected from the biological sample;

a fixed reflecting device;

a reference light path receptive to said broadband light from said broadband light source, said reference light path configured to direct said broadband light at said fixed reflecting device and to receive said broadband light reflected from said fixed reflecting device, said reference light path and said sensing light path cooperating to define a target depth;

means for modulating at about a distance of a center wavelength of said broadband light an effective light path length of at least one of said reference light path and said sensing light path with respect to said target depth;

a detector receptive to said broadband light resulting from said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate a signal indicative of an interference of said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, said signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said target depth;

wherein said means for modulating is such that said phase component of said signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said target depth;

means for changing said effective light path length of at least one of said reference light path and said sensing light path to define an other target depth, said other target depth is at a distance of about at least a coherence length of said broadband light from said target depth;

wherein said means for modulating further modulates at about a distance of the center wavelength of said broadband light said effective light path length of at least one of said reference light path and said sensing light path with respect to said other target depth;

wherein said detector is further receptive to said broadband light resulting from said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate an other signal indicative of an interference of said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device, said other signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said other target depth;

wherein said means for modulating is such that said phase component of said other signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said other target depth; and

processing means configured to determine the characteristic of the analyte in the biological sample from variations in said intensity measurements.

9. The system of claim 8 wherein said processing means is further configured to determine a scattering coefficient from said variations in said intensity measurements and the characteristic of the analyte in the biological sample from said scattering coefficient.

10. The system of claim 8 wherein said effective light path length of said reference light path and said effective light path length of said sensing light path defines said target depth.

11. The system of claim 10 wherein said effective light path length of at least one of said reference light path and said sensing light path having been changed defines said other target depth.

12. The system of claim 8 wherein at least one of said reference light path and said sensing light path comprises at least one of an optical fiber and a waveguide.

13. The system of claim 8 wherein said means for modulating comprises metallic electrodes disposed at an optical waveguide and an optical fiber wound on a piezoelectric drum forming at least a portion of at least one of said reference light path and said sensing light path.

14. The system of claim 8 further including a calibrating strip for calibrating at least one of said reference light path and said sensing light path by adjusting effective light path length of at least one of said reference light path and said sensing light path based on a sample exhibiting properties including at least one of known refractive index and scattering coefficient.

15. A method for determining a characteristic of an analyte in a biological sample, die method comprising:

directing broadband light by means of a sensing light path at the biological sample, at a target depth defined by said sensing light path and a reference light path;

receiving said broadband light reflected from the biological sample by means of said sensing light path;

directing said broadband light by means of said reference light path at a fixed reflecting device;

receiving said broadband light reflected from said fixed reflecting device by means of said reference light path;

modulating at about a distance of a center wavelength of said broadband light an effective light path length of at least one of said reference light path and said sensing light path with respect to said target depth;

detecting said broadband light resulting from said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate a signal indicative of an interference of said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, said signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said target depth;

wherein said effective light path length of at least one of said reference light path and said sensing light path is modulated such that said phase component of said signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said target depth;

changing said effective light path length of at least one of said reference light path and said sensing light path to define an other target depth, said other target depth is at a distance of about at least a coherence length of the broadband light from said target depth;

modulating at about a distance of a center wavelength of said broadband light said effective light path length of at least one of said reference light path and said sensing light path with respect to said other target depth;

detecting said broadband light resulting from said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate an other signal indicative of an interference of said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device for said other target depth, said other signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said other target depth;

wherein said effective light path length of at least one of said reference light path and said sensing light path is modulated such that said phase component of said other signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said other target depth;

determining a scattering coefficient from said variations in said intensity measurements; and

determining the characteristic of the analyte in the biological sample from said scattering coefficient; and

diagnosing a human condition from the characteristic.

16. The method of claim 15 wherein said target depth is defined by said effective light path length of said reference light path and said effective light path length of said sensing light path.

17. The method of claim 16 wherein said other target depth is defined by said effective light path length of at least one of said reference light path and said sensing light path having been changed.

18. The method of claim 15 wherein at least one of said reference light path and said sensing light path comprises at least one of an optical fiber and a waveguide.

19. The method of claim 15 wherein at least one of said modulating employs at least one metallic electrodes disposed at an optical waveguide and an optical fiber wound on a piezoelectric drum forming at least a portion of at least one of said reference light path and said sensing light path.

20. The method of claim 15 further including calibrating at least one of said reference light path and said sensing light path by adjusting effective light path length of at least one of said reference light path and said sensing light path based on a sample exhibiting properties including at least one of known refractive index and scattering coefficient.

21. A system for determining a characteristic of an analyte in a biological sample, the system comprising:

a broadband light source for providing a broadband light;

a sensing light path receptive to said broadband light from said broadband light source, said sensing light path configured to direct said broadband light at the biological sample and to receive said broadband light reflected from the biological sample;

a fixed reflecting device;

a reference light path receptive to said broadband light from said broadband light source, said reference light path configured to direct said broadband light at said fixed reflecting device and to receive said broadband light reflected from said fixed reflecting device, said reference light path and said sensing light path cooperating to define a target depth;

means for modulating at about a distance of a center wavelength of said broadband light an effective light path length of at least one of said reference light path and said sensing light path with respect to said target depth;

a detector receptive to said broadband light resulting from said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate a signal indicative of an interference of said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, said signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said target depth;

wherein said means for modulating is such that said phase component of said signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said target depth;

means for changing said effective light path length of at least one of said reference light path and said sensing light path to define an other target depth, said other target depth is at a distance of about at least a coherence length of the broadband light from said target depth;

wherein said means for modulating further modulates said effective light path length of at least one of said reference light path and said sensing light path with respect to said other target depth;

wherein said detector is further receptive to said broadband light resulting from said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate an other signal indicative of an interference of said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device, said other signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said other target depth;

wherein said means for modulating is such that said phase component of said other signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said other target depth; and

processing means configured to determine a scattering coefficient from said variations in said intensity measurements and the characteristic of the analyte in the biological sample from said scattering coefficient.

22. The system of claim 21 wherein said effective light path length of said reference light path and said effective light path length of said sensing light path defines said target depth.

23. The system of claim 22 wherein said effective light path length of at least one of said reference light path and said sensing light path having been changed defines said other target depth.

24. The system of claim 21 wherein at least one of said reference light path and said sensing light path comprises at least one of an optical fiber and a waveguide.

25. The system of claim 21 wherein said means for modulating comprises metallic electrodes disposed at an optical waveguide and an optical fiber wound on a piezoelectric drum forming at least a portion of at least one of said reference light path and said sensing light path.

26. The system of claim 21 further including a calibrating strip for calibrating at least one of said reference light path and said sensing light path by adjusting effective light path length of at least one of said reference light path and said sensing light path based on a sample exhibiting properties including at least one of known refractive index and scattering coefficient.

27. A method for determining a characteristic of an analyte in a biological sample, the method comprising:

directing broadband light by means of a sensing light path at the biological sample, at a target depth defined by said sensing light path and a reference light path;

receiving said broadband light reflected from the biological sample by means of said sensing light path;

directing said broadband light by means of said reference light path at a fixed reflecting device;

receiving said broadband light reflected from said fixed reflecting device by means of said reference light path;

modulating at about a distance of a center wavelength of said broadband light an effective light path length of at least one of said reference light path and said sensing light path with respect to said target depth;

detecting said broadband light resulting from said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate a signal indicative of an interference of said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, said signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said target depth;

wherein said effective light path length of at least one of said reference light path and said sensing light path is modulated such that said phase component of said signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said target depth;

changing said effective light path length of at roast one of said reference light path and said sensing light path to define an other target depth, said other target depth is at a distance of about at least a coherence length of the broadband light from said target depth;

modulating at about a distance of a center wavelength of said broadband light said effective light path length of at least one of said reference light path and said sensing light path with respect to said other target depth;

detecting said broadband light resulting from said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate an other signal indicative of an interference of said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device for said other target depth, said other signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said other target depth;

wherein said effective light path length of at least one of said reference light path and said sensing light path is modulated such that said phase component of said other signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said other target depth;

determining the characteristic of the analyte in the biological sample from variations in said intensity measurements; and

calibrating at least one of said reference light path and said sensing light path by adjusting effective light path length of at least one of said reference light path and said sensing light path based on a sample exhibiting properties including at least one of known refractive index and scattering coefficient.

28. The method of claim 27 wherein said target depth is defined by said effective light path length of said reference light path and said effective light path length of said sensing light path.

29. The method of claim 28 wherein said other target depth is defined by said effective light path length of at least one of said reference light path and said sensing light path having been changed.

30. The method of claim 27 wherein at least one of said reference light path and said sensing light path comprises at least one of an optical fiber and a waveguide.

31. The method of claim 27 wherein at least one of said modulating employs at least one metallic electrodes disposed at an optical waveguide and an optical fiber wound on a piezoelectric drum forming at least a portion of at least one of said reference light path and said sensing light path.

32. A system for determining a characteristic of an analyte in a biological sample, the system comprising:

a broadband light source for providing a broadband light;

a sensing light path receptive to said broadband light from said broadband light source, said sensing light path configured to direct said broadband light at the biological sample and to receive said broadband light reflected from the biological sample;

a fixed reflecting device;

a reference light path receptive to said broadband light from said broadband light source, said reference light path configured to direct said broadband light at said fixed reflecting device and to receive said broadband light reflected from said fixed reflecting device, said reference light path and said sensing light path cooperating to define a target depth;

means for modulating at about a distance of a center wavelength of said broadband light an effective light path length of at least one of said reference light path and said sensing light path with respect to said target depth;

a detector receptive to said broadband light resulting from said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate a signal indicative of an interference of said broadband light reflected from said target depth in the biological sample and said broadband light reflected from said fixed reflecting device, said signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said target depth;

wherein said means for modulating is such that said phase component of said signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said target depth;

means for changing said effective light path length of at least one of said reference light path and said sensing light path to define an other target depth, said other target depth is at a distance of about at least a coherence length of the broadband light from said target depth;

wherein said means for modulating further modulates said effective light path length of at least one of said reference light path and said sensing light path with respect to said other target depth;

wherein said detector is further receptive to said broadband light resulting from said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device, to generate an other signal indicative of an interference of said broadband light reflected from said other target depth in the biological sample and said broadband light reflected from said fixed reflecting device, said other signal having a phase component and an amplitude component, said amplitude component comprises an intensity measurement at said other target depth;

wherein said means for modulating is such that said phase component of said other signal is sinusoidal and its magnitude generally proportional to said intensity measurement at said other target depth; and

processing means configured to determine the characteristic of the analyte in the biological sample from variations in said intensity measurements; and

a calibrating strip for calibrating at least one of said reference light path and said sensing light path by adjusting effective light path length of at least one of said reference light path and said sensing light path based on a sample exhibiting properties including at least one of known refractive index and scattering coefficient.

33. The system of claim 32 wherein said effective light path length of said reference light path and said effective light path length of said sensing light path defines said target depth.

34. The system of claim 33 wherein said effective light path length of at least one of said reference light path and said sensing light path having been changed defines said other target depth.

35. The system of claim 32 wherein at least one of said reference light path and said sensing light path comprises at least one of an optical fiber and a waveguide.

36. The system of claim 32 wherein said means for modulating comprises metallic electrodes disposed at an optical waveguide and an optical fiber wound on a piezoelectric drum forming at least a portion of at least one of said reference light path and said sensing light path.