WO2004064627B1 - In vivo raman endoscopic probe and methods of use - Google Patents

In vivo raman endoscopic probe and methods of use

Info

Publication number
WO2004064627B1
WO2004064627B1 PCT/CA2004/000062 CA2004000062W WO2004064627B1 WO 2004064627 B1 WO2004064627 B1 WO 2004064627B1 CA 2004000062 W CA2004000062 W CA 2004000062W WO 2004064627 B1 WO2004064627 B1 WO 2004064627B1
Authority
WO
WIPO (PCT)
Prior art keywords
filter
illumination light
pass
band
notch
Prior art date
Application number
PCT/CA2004/000062
Other languages
French (fr)
Other versions
WO2004064627A1 (en
Inventor
Haishan Zeng
Original Assignee
Spectravu Medical Inc
Haishan Zeng
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 Spectravu Medical Inc, Haishan Zeng filed Critical Spectravu Medical Inc
Publication of WO2004064627A1 publication Critical patent/WO2004064627A1/en
Publication of WO2004064627B1 publication Critical patent/WO2004064627B1/en

Links

Classifications

    • 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
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • A61B5/0086—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters using infrared radiation
    • 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
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • 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
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • G01N2021/653—Coherent methods [CARS]
    • G01N2021/656—Raman microprobe

Abstract

An apparatus for in vivo, endoscopic laser Raman spectroscopy probe and methods for its use are described. The probe comprises a fiber bundle assembly small enough to fit through an endoscope instrument channel, a novel combination of special coatings to the fiber bundle assembly, including a short-pass filter on the illumination fiber and a long-pass filter on the collection fiber bundle, a novel filter adapter comprising collimating lenses, focusing lenses, a band-pass filter, and a notch filter, and a round-to-parabolic linear array fiber bundle. The apparatus further comprises a laser to deliver illumination light and a spectrometer to analyze Raman-scattered light from a sample. The analysis of Raman spectra from in vivo measurements can discover molecular and structural changes associated with neoplastic transformations and lead to early diagnosis and treatment of cancer.

Claims

AMENDED CLAIMS[Received by the International Bureau on 26 July 2004 (26.07.04): original claims 1 - 65 replaced by amended claims 1 - 59;(8 pages)] + 1 claιm: STATEMENT
1. An in vivo Raman endoscope comprising:
a probing fiber bundle having a distal end and a proximal end and comprising at least one illumination fiber and a plurality of collection fibers,
a short-pass coating filter on the distal end of said at least one illumination fiber,
a long-pass coating filter on the distal end of said plurality of collection fibers,
a filter adapter on the proximal end of said fiber bundle, comprising a band-pass filter in optical communication with said illumination fiber and a notch filter in optical communication with said plurality of collection fibers, and
a round-to-parabolic linear array fiber bundle in optical communication with said plurality of collection fibers through said notch filter.
2. The system of claim 1, wherein said short-pass filter has a cut-off wavelength of about 825 mn.
3. The system of claim 1, wherein said long-pass filter has a cut-off wavelength of about 825 nm.
4. The system of claim 1, wherein said short-pass filter has a cut-off wavelength of about 825 nm and said long-pass filter has a cut-off wavelength of about 825 nm.
5. The system of claim 1, wherein said band-pass filter transmits in a range around 785 nm.
6. The system of claim 5, wherein said range is plus-or-minus 2.5 nm.
27
7. The system of claim 1, wherein said notch filter has an OD greater than 6.0 at 785 nm.
8. The system of claim 1, further comprising means for delivering illumination light to said filter adapter and wherein said filter adapter further comprises a collimating lens between said means for delivering and said band-pass filter.
9. The system of claim 8, wherein said means for delivering comprises a laser.
10. The system of claim 8, further comprising a focusing lens between said bandpass filter and said illumination fiber.
11. The system of claim 1, wherein said filter adapter further comprises a collimating lens between said plurality of collection fibers and said notch filter.
12. The system of claim 11, further comprising a focusing lens between said notch filter and said round-to-parabolic linear array fiber bundle.
13. The system of claim 1, further comprising means for delivering illumination light to said filter adapter and said filter adapter further comprises a collimating lens between said means for delivering and said band-pass filter, a focusing lens between said band-pass filter and said illumination fiber, a collimating lens between said plurality of collection fibers and said notch filter, and a focusing lens between said notch filter and said round-to-parabolic linear array fiber bundle.
14. The system of claim 1, further comprising a quartz window at the distal end of said fiber bundle.
15. The system of claim 8, wherein said illumination light is chosen at a wavelength to induce Raman scattering.
16. The system of claim 15, wherein said illumination light is monochromatic.
17. The system of claim 16, wherein said light source is a laser.
18. The system of claim 17, wherein said laser is a diode laser.
19. The system of claim 18, wherein said illumination light is about 785 nm.
20. An in vivo Raman endoscopic probe system, comprising:
a probe comprising a probing fiber bundle having a distal end and a proximal end and comprising at least one illumination fiber and a plurality of collection fibers,
a short-pass coating filter on the distal end of said at least one illumination fiber,
a long-pass coating filter on the distal end of said plurality of collection fibers,
a filter adapter on the proximal end of said fiber bundle, comprising a band-pass filter in optical communication with said illumination fiber and a notch filter in optical communication with said plurality of collection fibers,
a round-to-parabolic linear array fiber bundle in optical communication with said plurality of collection fibers through said notch filter,
a light source providing illumination light to said illumination fiber through said band-pass filter,
a spectrometer in optical communication with said plurality of collection fibers through said notch filter.
29
21. The system of claim 20, wherein said short-pass filter has a cut-off wavelength of about 825 nm.
22. The system of claim 20, wherein said long-pass filter has a cut-off wavelength of about 825 nm.
23. The system of claim 20, wherein said short-pass filter has a cut-off wavelength of about 825 nm and said long-pass filter has a cut-off wavelength of about 825 mn.
24. The system of claim 20, wherein said band-pass filter transmits in a range around 785 nm.
25. The system of claim 24, wherein said range is plus-or-minus 2.5 nm.
26. The system of claim 20, wherein said notch filter has an OD greater than 6.0 at 785 nm.
27. The system of claim 20, further comprising means for delivering illumination light to said filter adapter and wherein said filter adapter further comprises a collimating lens between said means for delivering and said band-pass filter.
28: The system of claim 27, wherein said means for delivering comprises a laser.
29. The system of claim 27, further comprising a focusing lens between said bandpass filter and said illumination fiber.
30. The system of claim 20, wherein said filter adapter further comprises a collimating lens between said plurality of collection fibers and said notch filter.
31. The system of claim 30, further comprising a focusing lens between said notch filter and said round-to-parabolic linear array fiber bundle.
30
32. The system of claim 20, further comprising means for delivering illumination light to said filter adapter and said filter adapter further comprises a collimating lens between said means for delivering and said band-pass filter, a focusing lens between said band-pass filter and said illumination fiber, a collimating lens between said plurality of collection fibers and said notch filter, and a focusing lens between said notch filter and said round-to-parabolic linear array fiber bundle.
33. The system of claim 20, further comprising a quartz window at the distal end of said fiber bundle.
34. The system of claim 20, wherein said illumination light is chosen to induce Raman scattering.
35. The system of claim 31 , wherein said illumination light is monochromatic.
36. The system of claim 31 , wherein said light source is a laser.
37. The system of claim 33, wherein said laser is a diode laser.
38. The system of claim 40, wherein said illumination light is about 785 nm.
39. The system of claim 20, wherein said plurality of collection fibers have a core diameter of about 100 μm.
40. The system of claim 20, wherein the number and core diameter of said plurality of collection fibers are selected to fill the vertical height of a detector of said spectrometer.
41. The system of claim 37, wherein said detector is a CCD.
31
42. A method of measuring Raman spectra in vivo, comprising the following:
providing illumination light,
band-pass filtering said illumination light to reduce background Raman and fluorescence signals,
short-pass filtering said illumination light with a coating filter to reduce background Raman and fluorescence signals,
illuminating a subject with said illumination light to induce measurable Raman scattered light,
collecting a sample of light comprising said Raman scattered light,
long-pass filtering said sample with a coating filter to reduce reflected light,
notch filtering said sample to reduce reflected light,
providing said sample with a substantially inverse shape that is complementary to a distortion to said sample caused by passing said sample through a light- dispersive element,
passing said sample through a plane grating to provide substantially straight spectral lines, and
performing Raman spectroscopic analysis on said substantially straight lines.
43. The method of claim 42, wherein said short-pass filtering step comprises attenuating wavelengths above 825 nm.
44. The method of claim 42, wherein said long-pass filtering step comprises
32 attenuating wavelengths below about 825 nm.
45. The method of claim 44, wherein said short-pass filtering step comprises attenuating wavelengths above 825 nm.
46. The method of claim 42, wherein said band-pass filtering step comprises transmitting in a range around 785 nm.
47. The method of claim 46, wherein said range is plus-or-minus 2.5 nm.
48. The method of claim 42, wherein said notch filtering step comprises attenuating at an OD greater than 6.0 at 785 nm.
49. The method of claim 42, further comprising providing a quartz window between said subject and said illumination light.
50. The method of claim 42, further comprising selecting said illumination light to induce Raman scattering.
51. The method of claim 50, wherein said illumination light is monochromatic.
52. The method of claim 50, further comprising providing said illumination light from a laser.
53. The method of claim 52, wherein said laser is a diode laser.
54. The method of claim 53, wherein said illumination light is about 785 mn.
55. The method of claim 42, further comprising collimating said illumination light before said band-pass filtering step.
56. The method of claim 55, further comprising focusing said illumination light
33 after said band-pass filtering step.
57. The method of claim 42, further comprising collimating said sample before said notch filtering step.
58. The method of claim 57, further comprising focusing said sample after said notch filtering step.
59. The method of claim 42, further comprising collimating said illumination light before said band-pass filtering step, focusing said illumination light after said band-pass filtering step, collimating said sample before said notch filtering step, and focusing said sample after said notch filtering step.
34
PCT/CA2004/000062 2003-01-21 2004-01-21 In vivo raman endoscopic probe and methods of use WO2004064627A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US44156603P 2003-01-21 2003-01-21
US60/441,566 2003-01-21

Publications (2)

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WO2004064627A1 WO2004064627A1 (en) 2004-08-05
WO2004064627B1 true WO2004064627B1 (en) 2004-10-14

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WO (1) WO2004064627A1 (en)

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US7383077B2 (en) 2008-06-03
US20040152992A1 (en) 2004-08-05
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