US6208886B1
Expired / Lapsed
US
⏱️ 0.0 years remaining
Non-linear optical tomography of turbid media
Assignee: Alfano Optical Tomography LLC
•
Filing: 1998-04-03
•
Granted: 2001-03-27
•
Expires: 2018-04-03
Abstract
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.
Inventors
- 👤 Robert R. Alfano
- 👤 Yici Guo
- 👤 Feng Liu
- 👤 Ping Pei Ho
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 12:00
CPC Classifications
A; A61; A61B; A61B5/00; A61B5/0059; A61B5/0073; A61B5/45; A61B5/4519
Claims Analysis
Total Claims: 43
Claim 1
Independent Claim
119 words
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.
Claim 2
Independent Claim
119 words
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.
Claim 3
Dependent Claim
29 words
The apparatus as claimed in claim 1 wherein said scanning means comprises a laser and wherein said laser and said selectively passing means are arranged in a backscatter geometry.
Claim 4
Dependent Claim
29 words
The apparatus as claimed in claim 1 wherein said scanning means comprises a laser and wherein said laser and said selectively passing means are arranged in a transmission geometry.
Claim 5
Dependent Claim
32 words
The apparatus as claimed in claim 1 wherein said scanning means comprises a laser and an optical fiber, said optical fiber having an input end coupled to the output from said laser.
Claim 6
Dependent Claim
40 words
The apparatus as claimed in claim 1 wherein said scanning means comprises a laser for illuminating the sample with fundamental and second-harmonic laser light pulses, said fundamental laser light pulses having a wavelength in the range of approximately 400-1400 nm.
Claim 7
Dependent Claim
37 words
The apparatus as claimed in claim 5 wherein said laser is selected from the group consisting of Ti:Sapphire, Cr 4+ :Forsterite, Nd:YAG, Cr:YAG, Cr 4+ :Ca 2 GeO 4 , colliding pulse mode-lock, and semiconductor diode lasers.
Claim 8
Dependent Claim
33 words
The apparatus as claimed in claim 5 wherein said scanning means further comprises a stage, the sample being mounted on said stage, said stage being movable in the x, y and z directions.
Claim 9
Dependent Claim
30 words
The apparatus as claimed in claim 7 wherein said scanning means further comprises an optical fiber, said optical fiber having an input end coupled to the output from said laser.
Claim 10
Dependent Claim
55 words
The apparatus as claimed in claim 5 wherein said scanning means further comprises means, optically coupled to the output of said laser, for causing the output of said laser to scan in the x and y directions and a stage, the sample being mounted on said stage, said stage being movable in the z direction.
Claim 11
Dependent Claim
29 words
The apparatus as claimed in claim 9 wherein said means for causing the output of said laser to scan in the x and y directions comprises a rotating mirror.
Claim 12
Dependent Claim
32 words
The apparatus as claimed in claim 1 wherein said selectively passing means comprises band pass filters selective for said at least second-order harmonic wave light and said fluorescence due to multi-photon excitation.
Claim 13
Dependent Claim
39 words
The apparatus as claimed in claim 1 wherein said detecting means comprises a pair of detectors, each of said detectors being a detector selected from the group consisting of a photomultiplier, a CCD camera and an intensified CCD camera.
Claim 14
Dependent Claim
32 words
The apparatus as claimed in claim 1 wherein said selectively passing means comprises a spectrograph and wherein said detecting means comprises an arrayed photodetector, a CCD camera and an intensified CCD camera.
Claim 15
Independent Claim
108 words
A method for constructing a three-dimensional tomographic map of a sample, said method comprising the steps of: (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.
Claim 16
Independent Claim
108 words
A method for constructing a three-dimensional tomographic map of a sample, said method comprising the steps of: (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.
Claim 17
Dependent Claim
15 words
The method as claimed in claim 14 wherein the sample is a biological tissue sample.
Claim 18
Dependent Claim
17 words
The method as claimed in claim 15 wherein the sample is an in vivo biological tissue sample.
Claim 19
Dependent Claim
17 words
The method as claimed in claim 15 wherein the sample is an in vitro biological tissue sample.
Claim 20
Dependent Claim
42 words
The method as claimed in claim 15 wherein the sample is a biological tissue sample obtained from a part of the body selected from the group consisting of the skin, the cervix, the vagina, the gastrointestinal tract, the prostate and the bladder.
Claim 21
Dependent Claim
18 words
The method as claimed in claim 15 wherein the biological tissue sample has no extrinsic fluorophors added thereto.
Claim 22
Dependent Claim
22 words
The method as claimed in claim 15 wherein said three-dimensional tomographic map also maps the carcinomatoid state of the biological tissue sample.
Claim 23
Dependent Claim
40 words
The method as claimed in claim 14 wherein said scanning step comprises illuminating the sample using a laser emitting fundamental and second-harmonic laser light pulses, said fundamental laser light pulses having a wavelength in the range of approximately 400-1400 nm.
Claim 24
Dependent Claim
40 words
The method as claimed in claim 21 wherein said scanning step comprises illuminating the sample using a laser emitting fundamental and second-harmonic laser light pulses, said fundamental laser light pulses having a wavelength in the range of about 560-630 nm.
Claim 25
Dependent Claim
40 words
The method as claimed in claim 21 wherein said scanning step comprises illuminating the sample using a laser emitting fundamental and second-harmonic laser light pulses, said fundamental laser light pulses having a wavelength in the range of about 680-700 nm.
Claim 26
Dependent Claim
40 words
The method as claimed in claim 21 wherein said scanning step comprises illuminating the sample using a laser emitting fundamental and second-harmonic laser light pulses, said fundamental laser light pulses having a wavelength in the range of about 700-740 nm.
Claim 27
Dependent Claim
40 words
The method as claimed in claim 21 wherein said scanning step comprises illuminating the sample using a laser emitting fundamental and second-harmonic laser light pulses, said fundamental laser light pulses having a wavelength in the range of about 900-940 nm.
Claim 28
Dependent Claim
40 words
The method as claimed in claim 21 wherein said scanning step comprises illuminating the sample using a laser emitting fundamental and second-harmonic laser light pulses, said fundamental laser light pulses having a wavelength in the range of about 700-730 nm.
Claim 29
Dependent Claim
40 words
The method as claimed in claim 21 wherein said scanning step comprises illuminating the sample using a laser emitting fundamental and second-harmonic laser light pulses, said fundamental laser light pulses having a wavelength in the range of about 500-560 nm.
Claim 30
Dependent Claim
40 words
The method as claimed in claim 21 wherein said scanning step comprises illuminating the sample using a laser emitting fundamental and second-harmonic laser light pulses, said fundamental laser light pulses having a wavelength in the range of about 1200-1400 nm.
Claim 31
Dependent Claim
20 words
The method as claimed in claim 14 wherein said scanning and selectively passing steps are performed using a transmission geometry.
Claim 32
Dependent Claim
20 words
The method as claimed in claim 14 wherein said scanning and selectively passing steps are performed using a backscattering geometry.
Claim 33
Dependent Claim
44 words
The method as claimed in claim 14 wherein said scanning step comprises mounting the sample on a stage, said stage being movable in the x, y and z directions, and illuminating the sample while moving said stage in the x, y and z directions.
Claim 34
Dependent Claim
50 words
The method as claimed in claim 14 wherein the sample is mounted on a stage, said stage being movable in the z direction, and wherein said scanning step comprises illuminating the sample with a scanning beam in the x and y directions while moving the stage in the z direction.
Claim 35
Independent Claim
207 words
An apparatus for use in constructing a tomographic map of a turbid medium, said apparatus comprising: (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.
Claim 36
Independent Claim
207 words
An apparatus for use in constructing a tomographic map of a turbid medium, said apparatus comprising: (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.
Claim 37
Independent Claim
139 words
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: (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.
Claim 38
Independent Claim
139 words
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: (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.
Claim 39
Dependent Claim
33 words
The apparatus as claimed in claim 1 wherein the sample is a biological tissue sample and wherein said mapping means also comprises means for mapping the carcinomatoid state of the biological tissue sample.
Claim 40
Independent Claim
164 words
An apparatus for use in constructing a three-dimensional tomographic map of a sample, said apparatus comprising: (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.
Claim 41
Independent Claim
164 words
An apparatus for use in constructing a three-dimensional tomographic map of a sample, said apparatus comprising: (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.
Claim 42
Independent Claim
189 words
An apparatus for use in constructing a three-dimensional tomographic map of a sample, said apparatus comprising: (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.
Claim 43
Independent Claim
189 words
An apparatus for use in constructing a three-dimensional tomographic map of a sample, said apparatus comprising: (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.
References Cited (Backward Citations)
US5034613A
Cited
US5699798A
Cited
US5371368A
Cited
US5813988A
Cited
US5999836A
Cited
US5813987A
Cited
US5865754A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2004-03-26 | 2004-09-25 | 2005-03-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2008-03-26 | 2008-09-25 | 2009-03-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2012-03-26 | 2012-09-25 | 2013-03-27 | $7700.00 | Window Closed / Lapsed |