Non-linear optical tomography of turbid media
DCFirst Claim
1. An apparatus for use in constructing a three-dimensional tomographic map of a sample, said apparatus comprising:
- (a) means for scanning the sample with a focused beam of laser light in x, y and z directions, said light emerging from the sample comprising fundamental light, at least second-order harmonic wave light, and fluorescence due to multi-photon excitation;
(b) means for selectively passing only said at least second-order harmonic wave light and said fluorescence due to multi-photon excitation;
(c) means for individually detecting each of said at least second-order harmonic wave light and said fluorescence due to multi-photon excitation selectively passed; and
(d) means for generating a three-dimensional tomographic map of the sample using the light detected by said detecting means.
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Abstract
An apparatus utilizing non-linear optical signals for use in constructing a three-dimensional tomographic map of an in vivo biological tissue for medical disease detection purposes. In one embodiment, said apparatus comprises a stage for supporting the in vivo biological tissue; a laser for illuminating the in vivo biological tissue with a focused beam of laser light, the light emerging from the in vivo biological tissue comprising fundamental light, harmonic wave light, and fluorescence due to multi-photon excitation; a filter for selectively passing only at least one of the harmonic wave light and the fluorescence; one or more detectors for individually detecting each of the harmonic wave light and the fluorescence selectively passed; and a mechanism for moving the laser relative to the stage in x, y and z directions.
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Citations
37 Claims
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1. An apparatus for use in constructing a three-dimensional tomographic map of a sample, said apparatus comprising:
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(a) means for scanning the sample with a focused beam of laser light in x, y and z directions, said light emerging from the sample comprising fundamental light, at least second-order harmonic wave light, and fluorescence due to multi-photon excitation;
(b) means for selectively passing only said at least second-order harmonic wave light and said fluorescence due to multi-photon excitation;
(c) means for individually detecting each of said at least second-order harmonic wave light and said fluorescence due to multi-photon excitation selectively passed; and
(d) means for generating a three-dimensional tomographic map of the sample using the light detected by said detecting means. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 35)
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14. A method for constructing a three-dimensional tomographic map of a sample, said method comprising the steps of:
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(a) scanning the sample with a focused beam of laser light in x, y and z directions, said light emerging from the sample comprising fundamental light, at least second-order harmonic wave light, and fluorescence due to multi-photon excitation;
(b) selectively passing only said at least second-order harmonic wave light and said fluorescence due to multi-photon excitation;
(c) individually detecting each of said at least second-order harmonic wave light and said fluorescence due to multi-photon excitation selectively passed; and
(d) generating a three-dimensional tomographic map of the sample using the light detected. - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
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33. An apparatus for use in constructing a tomographic map of a turbid medium, said apparatus comprising:
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(a) means for illuminating said turbid medium with a focused beam of laser light, said light emerging from said turbid medium comprising fundamental light, at least second-order harmonic wave light, and fluorescence due to multi-photon excitation;
(b) means for collecting the light emerging from said turbid medium;
(c) means for splitting said collected light into a first beam and a second beam;
(d) a first filter disposed along the path of said first beam for selectively passing only said at least second-order harmonic wave light;
(e) a second filter disposed along the path of said second beam for selectively passing only said fluorescence due to mutli-photon excitation;
(f) a first detector disposed along the path of said first beam after said first filter;
(g) a second detector disposed along the path of said second beam after said second filter;
(h) means for bringing said filtered light of said first beam to focus on said first detector;
(i) means for bringing said filtered light of said second beam to focus on said second detector; and
(j) means for generating a tomographic map using the light detected by said first and second detectors.
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34. An apparatus utilizing non-linear optical signals for use in constructing a three-dimensional tomographic map of a biological tissue for medical disease detection purposes, said apparatus comprising:
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(a) means for supporting said biological tissue;
(b) means for illuminating said biological tissue with a focused beam of laser light, said light emerging from said biological tissue comprising fundamental light, at least second-order harmonic wave light, and fluorescence due to multi-photon excitation;
(c) detector means;
(d) means for collecting said emergent light and bringing said collected light to focus on said detector means;
(e) filter means disposed between said detector means and said collecting means for selectively passing only said at least second-order harmonic wave light;
(f) a 1-dimensional scanning translation stage for supporting said collecting means; and
(g) a PZT device or scanning galvanometer for x-y scanning of said focused beam.
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36. An apparatus for use in constructing a three-dimensional tomographic map of a sample, said apparatus comprising:
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(a) a pulsed laser for generating a beam of laser pulses along a first path;
(b) a dichroic beam splitter disposed along said first path for reflecting said beam of laser pulses along a second path and for selectively transmitting non-fundamental light from the sample, said sample being disposed along said second path;
(c) focusing means disposed along said second path for focusing said beam of laser pulses onto the sample, the light emerging from the sample comprising fundamental light, at least second-order harmonicwave light and fluorescence due to multi-photon excitation;
(d) a stage movable in x, y and z directions, the sample being mounted on said stage;
(e) means for detecting each of said at least second-order harmonic wave light and said fluorescence due to multi-photon excitation; and
(f) means for generating a three-dimensional tomographic map of the sample using the light detected by said detecting means.
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37. An apparatus for use in constructing a three-dimensional tomographic map of a sample, said apparatus comprising:
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(a) a pulsed laser for generating a beam of laser pulses along a first path;
(b) means, disposed along said first path, for causing said beam of laser pulses to scan in x and y directions along a second path;
(c) a dichroic beam splitter disposed along said second path for reflecting said scanning beam of laser pulses along a third path and for selectively transmitting non-fundamental light from the sample, said sample being disposed along said third path;
(d) focusing means disposed along said third path for focusing said scanning beam of laser pulses onto the sample, the light emerging from the sample comprising fundamental light, at least second-order harmonicwave light and fluorescence due to multi-photon excitation;
(e) a stage movable in the z direction, the sample being mounted on said stage;
(f) means for detecting each of said at least second-order harmonic wave light and said fluorescence due to multi-photon excitation; and
(g) means for generating a three-dimensional tomographic map of the sample using the light detected by said detecting means.
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Specification