Low coherence interferometry utilizing phase

• US 7,184,148 B2
• Filed: 05/14/2004
• Issued: 02/27/2007
• Est. Priority Date: 05/14/2004
• Status: Expired due to Fees

• Current Assignee: VZN Capital, LLC
• Original Assignee: Medeikon Corporation
• Inventors: Alphonse, Gerard A.
• Primary Examiner(s): Toatley, Jr.; Gregory J.
• Assistant Examiner(s): Lyons; Michael A.
• Application Number:
  US10/845,849
• Publication Number:
  US 20050254057A1
• Time in Patent Office: 1,019 Days
• Field of Search: 356/477, 356/479, 356/481, 356/517, 250/227.19, 250/227.27, 600/476
• 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 5/14546 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: G01N 21/45 using interferometric methods; using Schlieren methods
• CPC Class Codes: G01N 21/474 Details of optical heads therefor, e.g. using optical fibres
• CPC Class Codes: G01N 21/4785 Standardising light scatter apparatus; Standards therefor
• CPC Class Codes: G01N 21/49 within a body or fluid

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; and receiving the broadband light reflected from the biological sample by means of the sensing light path. The method also includes: directing the broadband light by means of the reference light path at a reflecting device; receiving the broadband light reflected from the reflecting device by means of the reference light path; and interfering the broadband light reflected from the biological sample and the broadband light reflected from the reflecting device. The method further includes: detecting the broadband light resulting from interference of the broadband light reflected from the biological sample and the broadband light reflected from the reflecting device; and modulating an effective light path length of at least one of the reference light path and the sensing light path to enhance interference of the broadband light reflected from the biological sample and the broadband light reflected from the reflecting device. The method continues with: determining a magnitude of change of the effective light path length introduced by the modulating when interference is enhanced; determining a variation in an index of refraction from a ratio of the magnitude of change of the effective light path length and the target depth; and determining the characteristic of the analyte in the biological sample from the variation in the index of refraction.

Claims

1. A method for diagnosing a human condition from 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 reflecting device;

receiving said broadband light reflected from said 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 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 reflecting device, wherein said signal is a product of a cosine function;

determining a phase component that is an argument of the cosine function;

determining a change in the phase component angle of said signal resulting from a change of said effective light path length that is itself induced by a change of a property of the biological sample;

determining a variation in an index of refraction from said change in the phase component of said signal;

determining the characteristic of the analyte in the biological sample from said variation in said index of refraction; and

diagnosing a human condition from the characteristic.

2. The method of claim 1 further comprising varying an 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 broadband light from said target depth.

3. The method of claim 2 wherein said varying an effective light path length of at least one of said reference light path and said sensing light path employs at least one of a modulator comprising metallic electrodes disposed at an optical waveguide and a modulator formed with 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 pat.

4. The method of claim 1 wherein said modulating comprises sinusoidal modulating.

5. The method of claim 1 wherein said modulating comprises ramp modulating.

6. The method of claim 1 wherein said target depth is defined as a difference between an effective light path length of said reference light path and an effective light path length of said sensing light path.

7. The method of claim 1 wherein said reflecting device comprises a fixed reflecting device.

8. 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.

9. The method of claim 1 wherein said modulating said effective light path length is achieved with at least one of a modulator comprising metallic electrodes disposed at an optical waveguide and a modulator formed with 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.

10. The method of claim 1:

wherein said modulating includes a phase parameter; and

further comprising relating said change in said phase component to said phase parameter, wherein said phase parameter is indicative of said variation in said index of refraction.

11. The method of claim 10 wherein said phase parameter is indicative of said variation in said index of refraction as a ratio of said phase parameter to said target depth.

12. 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.

13. The method of claim 1 wherein the characteristic of the analyte in the biological sample includes glucose concentration.

14. 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 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 reflecting device and to receive said broadband light reflected from said reflecting device, said reference light path and said sensing light path cooperating to define a target depth;

a modulator associated with at least one of said reference light path and said sensing light path, said modulator for modulating at about a distance of a center wavelength of said broadband light an effective light path length of said at least one of said reference light path and said sensing light path;

a detector receptive to said broadband light resulting from said broadband light reflected from the biological sample and said broadband light reflected from said reflecting device, said detector generating 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 reflecting device, wherein said signal is a product of a cosine function; and

processing means configured to determine a phase component that is an argument of the cosine function, said processing means further configured to determine a change in the phase component of said signal resulting from a change of said effective light path length that is itself induced by a change of a property of the biological sample, a variation in an index of refraction from said change in the phase component of said signal, and the characteristic of the analyte in the biological sample from said variation in said index of refraction.

15. The system of claim 14 further comprising

means for varying an 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.

16. The system of claim 15 wherein said means for varying comprises a modulator comprising metallic electrodes disposed at an optical waveguide and a modulator formed with 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.

17. The system of claim 14 wherein said modulator comprises a sinusoidal modulator.

18. The system of claim 14 wherein said modulator comprises a ramp modulator.

19. The system of claim 14 wherein said effective light path length of said sensing light path is different from said effective light path length of said sensing light path by a difference, said target depth defined as said difference.

20. The system of claim 14 wherein said reflecting device comprises a fixed reflecting device.

21. The system of claim 14 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.

22. The system of claim 14 wherein said modulator comprises at least one of metallic electrodes disposed at an optical waveguide and a plezoelectric drum with an optical fiber wound thereon forming at least a portion of at least one of said reference light path and said sensing light path.

23. The system of claim 14 wherein:

said modulator comprises modulating including a phase parameter; and

said processing means further configured to relate said change in said phase component to said phase parameter, wherein said phase parameter is indicative of said variation in said index of refraction.

24. The system of claim 14 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.

25. The system of claim 14 where in the characteristic of the analyte in the biological sample includes glucose concentration.