WO2005114149B1 - Low coherence interferometry utilizing phase - Google Patents

Low coherence interferometry utilizing phase

Info

Publication number
WO2005114149B1
WO2005114149B1 PCT/US2005/015372 US2005015372W WO2005114149B1 WO 2005114149 B1 WO2005114149 B1 WO 2005114149B1 US 2005015372 W US2005015372 W US 2005015372W WO 2005114149 B1 WO2005114149 B1 WO 2005114149B1
Authority
WO
WIPO (PCT)
Prior art keywords
light path
sensing
biological sample
broadband
reference light
Prior art date
Application number
PCT/US2005/015372
Other languages
French (fr)
Other versions
WO2005114149A1 (en
Inventor
Gerard A Alphonse
Original Assignee
Medeikon Corp
Gerard A Alphonse
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medeikon Corp, Gerard A Alphonse filed Critical Medeikon Corp
Publication of WO2005114149A1 publication Critical patent/WO2005114149A1/en
Publication of WO2005114149B1 publication Critical patent/WO2005114149B1/en

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
    • G01N21/45—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062—Arrangements for scanning
    • A61B5/0066—Optical coherence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4738—Diffuse reflection, e.g. also for testing fluids, fibrous materials
    • G01N21/474—Details of optical heads therefor, e.g. using optical fibres
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4785—Standardising light scatter apparatus; Standards therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/49—Scattering, i.e. diffuse reflection 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

AMENDED CLAIMS[received by the International Bureau on 30 November 2005 (30.11.2005); original claims 1, 15 amended, claims 4, 18, 29, 30-43, 44-58, claims renumbered and amended, present claims 12, 26 new ]What is claimed is:
Claim 1. A method far 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 reflecting device; receiving said broadband light reflected from said reflecting device by means of said reference light path; modulating 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, said signal having a phase component and an amplitude component; extracting the phase component of the signal; determining 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; determining a variation in an index of refraction from said change in the phase component of said signal; and determining the characteristic of the analyte in the biological sample from said variation in said index of refraction.
Claim 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.
Claim 3. The method of claim 2 wherein said varying an effective light pad 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 path.
Claim 4. The method of claim 1 wherein said modulating comprises sinusoidal modulating.
Claim 5. The method of claim 1 wherein said modulating comprises ramp modulating.
Claim 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.
Claim 7. The method of claim 6 wherein said effective light path length of said reference light path is longer than said effective light path length of said sensing light path.
Claim 8. The method of claim 1 wherein said reflecting device comprises a fixed reflecting device.
Claim 9. 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.
Claim 10. 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.
Claim 11. The method of claim 1 : wherein said modulating includes a phase parameter; and further comprising relating said change in the phase component of said signal to said phase parameter, wherein said phase parameter is indicative of said variation in said index of refraction.
Claim 12. The method of claim 11 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.
Claim 13. 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.
Claim 14. The method of Claim 1 wherein the characteristic of the analyte in the biological sample includes glucose concentration.
Claim 15. 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 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 said target depth in 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, said signal having a phase component and an amplitude component; and processing means configured to extract the phase component of the signal, 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.
Claim 16. The system of claim 15 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.
Claim 17. The system of claim 16 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.
Claim 18. The system of claim 15 wherein said modulator comprises a sinusoidal modulator.
Claim 19. The system of claim 15 wherein said modulator comprises a ramp modulator.
Claim 20. The system of claim 15 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.
Claim 21. The system of claim 20 wherein said effective light path length of said reference light path is longer than said effective light path length of said sensing light path by said difference.
Claim 22. The system of claim 15 wherein said reflecting device comprises a fixed reflecting device.
Claim 23. The system 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.
Claim 24. The system of claim 15 wherein said modulator comprises at least one of metallic electrodes disposed at an optical waveguide and a piezoelectric 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.
Claim 25. The system of claim 15 wherein: said modulator comprises modulating including a phase parameter; and said processing means further configured to relate said change in the phase component of said signal to said phase parameter, wherein said phase parameter is indicative of said variation in said index of refraction.
Claim 26. The system of claim 25 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.
Claim 27. The system of Claim 15 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 retractive index.
Claim 28. The system of Claim 15 where in the characteristic of the analyte in the biological sample includes glucose concentration.
PCT/US2005/015372 2004-05-14 2005-05-04 Low coherence interferometry utilizing phase WO2005114149A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/845,849 2004-05-14
US10/845,849 US7184148B2 (en) 2004-05-14 2004-05-14 Low coherence interferometry utilizing phase

Publications (2)

Publication Number Publication Date
WO2005114149A1 WO2005114149A1 (en) 2005-12-01
WO2005114149B1 true WO2005114149B1 (en) 2006-03-09

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