Raman Spectral Analysis Of Sub-Surface Tissues And Fluids
First Claim
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1. A method of determining, in vivo, one or more characteristics of a sub-surface tissue or fluid, through a diffusely scattering overlying tissue, comprising steps of:
- (a) supplying incident light at an entry region on a surface of the overlying tissue;
(b) collecting light scattered within the overlying tissue, from a collection region on the surface, the collection region being spaced from the entry region; and
(c) detecting, in the collected light, one or more Raman features, spectrally related to the incident light, which originate from the sub-surface tissue.
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Abstract
Apparatus and methods for determining, in-vivo, characteristics of sub-surface tissues or fluids in the human or animal body are disclosed. Incident radiation is supplied at one or more entry regions on a surface, and light is collected from one or more collection regions spaced from the entry regions. Raman features are detected in the collected light and depth related information derived therefrom.
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Citations
67 Claims
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1. A method of determining, in vivo, one or more characteristics of a sub-surface tissue or fluid, through a diffusely scattering overlying tissue, comprising steps of:
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(a) supplying incident light at an entry region on a surface of the overlying tissue;
(b) collecting light scattered within the overlying tissue, from a collection region on the surface, the collection region being spaced from the entry region; and
(c) detecting, in the collected light, one or more Raman features, spectrally related to the incident light, which originate from the sub-surface tissue. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15, 35, 36)
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13. The method of 1, wherein one or more entry regions surround a common collection region.
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16. A method of measuring, in-vivo, a sub-surface Raman spectrum of a diffusely-scattering tissue, the method comprising the steps of:
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a) irradiating the tissue with a light probe of incident radiation;
b) collecting light scattered by the tissue; and
c) spectrally separating at least a portion of the collected light to detect one or more Raman spectral features, wherein light scattered by the tissue is collected from a plurality of spatial locations on the surface of the tissue, each spatial location being at a different distance from the point of irradiation, at least a portion of the light collected at each spatial location being separately spectrally dispersed to form a plurality of Raman spectra and wherein the method further includes the step of;
d) analysing the plurality of Raman spectra to extract information on the Raman spectrum of a sub-surface region of the tissue. - View Dependent Claims (17, 33, 34)
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18. A method as claimed in 16, wherein the Raman spectrum for the chemical composition of the surface of the tissue is known and the Raman spectra are analysed by scaled subtraction of the known Raman spectrum from the Raman spectra of the collected light.
- 19. A method as claimed in 16, wherein the plurality of Raman spectra are analysed using multivariate data analysis.
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21. A method as claimed in 19, wherein at least twenty Raman spectra are collected at different distances from the point of irradiation.
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22. A method as claimed in 16, wherein the tissue is irradiated at two or more different wavelengths and the collected light is a combination of a Raman spectrum and fluorescence and wherein the method comprises the further step of extracting the Raman spectrum from the collected light.
- 23. A method as claimed in 16, wherein at least one of the tissue, the collection optics and the point or region of irradiation is moved relative to the others to enable the collection of Raman spectra at different distances from the point of irradiation.
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27. A method as claimed in 16, wherein the probe beam is supplied using optical fibres and the scattered light is collected using optical fibres arranged in a plurality of concentric circles around the probe beam optical fibres whereby the scattered light is collected in concentric rings at differing radii from the point of irradiation.
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28. A method as claimed in 16, wherein the collected light is spectrally dispersed using a spectrometer in combination with a CCD camera.
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29. A method as claimed in 16, wherein the light probe or incident radiation is generated using a cw laser.
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37. A method of carrying out an in-vivo sub-cutaneous inspection of a sub-surface tissue or fluid without surgical intervention, comprising:
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irradiating a surface tissue with a probe light beam;
collecting light scattered beneath the surface, from one or more collection regions on the surface spaced from the probe light beam; and
detecting one or more Raman spectral features from the collected light. - View Dependent Claims (38, 39)
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40. Apparatus for determining, in-vivo, one or more characteristics of a sub-surface tissue or fluid, through a diffusively scattering overlying tissue, comprising:
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a light source arranged to supply incident light at an entry region on a surface of the overlying tissue;
a collector arranged to collect light scattered, within the overlying tissue, from a collection region on the surface, the collection region being spaced from the entry region; and
a detector arranged to detect one or more Raman features spectrally related to the incident light, which originate from the sub-surface tissue or fluid. - View Dependent Claims (41, 42, 43, 50)
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44. The apparatus of 40, wherein the overlying tissue comprises at least one of skin and nail.
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45. The apparatus of 44, wherein the detector comprises a spectrometer arranged to spectrally disperse the collected light to separate out said Raman features.
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46. The apparatus of 40, wherein the detector comprises one or more filters arranged to select said Raman features.
- 47. The apparatus of 40 wherein either the entry region or the collection region is an annular region surrounding the other of the two regions.
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49. The apparatus of 40 further comprising a masking device arranged to controllably adjust the spacing between the entry region and the collection region.
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51. Apparatus for in-vivo selective measurement of Raman spectra generated at different depths within a diffusely-scattering tissue, the apparatus comprising:
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a light source (1) for irradiating the tissue with a probe beam of incident radiation;
collection optics for collecting light scattered by the tissue and passing it to a spectrometer;
detection means for detecting light dispersed by the spectrometer, wherein the apparatus is adapted for scattered light to be collected at a plurality of spatial locations on the surface of the tissue, each spatial location being at a different distance from the point of irradiation and at least a portion of the light collected at each spatial location being separately spectrally dispersed by the spectrometer (2) to form a plurality of Raman spectra and wherein the apparatus further includes an analyser (4) for identifying features specific to the Raman spectrum of a sub-layer of the tissue (6,7) from the plurality of Raman spectra. - View Dependent Claims (52, 53, 54)
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- 55. Apparatus as claimed in 51, further comprising a movable stage for relative movement of at least one of the tissue, the collection optics and the point of irradiation to enable the collection of Raman spectra at different distances from the point of irradiation.
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57. Apparatus as claimed in 51, wherein the collection optics comprises optical fibres arranged in a plurality of concentric circles around the probe beam.
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58. Apparatus as claimed in 51, wherein the light source is a cw laser.
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59. Apparatus as claimed in 51, wherein the detection means comprises a CCD camera.
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60. The apparatus of 40, wherein the incident radiation has a wavelength greater than 600 nm.
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61. The apparatus of 40, wherein the incident radiation has a wavelength greater than 800 nm.
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62. Medical sub-cutaneous inspection apparatus for carrying out an in-vivo inspection of a sub-surface tissue without surgical intervention, comprising:
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a probe light beam source arranged to irradiate a surface tissue;
a collector arranged to collect light scattered beneath the surface, from one or more collection regions on the surface spaced from the probe light beam; and
a detector arranged to detect one or more Raman spectral features from the collected light. - View Dependent Claims (63, 64)
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65. The apparatus of 40 implemented as an endoscope for inspection within the body by access through a natural or surgically formed orifice.
- 66. A method of diagnosis comprising collecting from a sample, consisting of a surface region of an overlying tissue and a sub-layer region of a deep tissue which is different to the overlying tissue, one or more Raman spectra using the method of 1.
Specification