US6839586B2
Expired / Lapsed
US
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Use of multiphoton excitation through optical fibers for fluorescence spectroscopy in conjunction with optical biopsy needles and endoscopes
Assignee: Cornell Research Foundation Inc
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Filing: 2003-05-05
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Granted: 2005-01-04
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Expires: 2023-05-05
Abstract
Abstract The present invention is directed to a method of applying radiation through an optical fiber for detecting disease within a plant or animal or imaging a particular tissue of a plant or animal. In addition, fluorescence can be detected and localized within a subject by such application of radiation through an optical fiber. The radiation is effective to promote simultaneous multiphoton excitation. The optical fibers are used alone to examine internal regions of tissue, in conjunction with an optical biopsy needle to evaluate sub-surface tissue, or with an endoscope to evaluate tissue within body cavities.
Inventors
- 👤 Watt W. Webb
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 07:17
CPC Classifications
G; G01; G01N; G01N21/00; G01N21/62; G01N21/63; G01N21/64; G01N21/6486; A; A61; A61B; A61B5/00; A61B5/0059; A61B5/0071; A61B5/0075; A61B5/0082; A61B5/0084; A61B5/0086; A61B5/68; A61B5/6846; A61B5/6847; A61B5/6848; G01N21/645; A61B1/00; A61B1/04; A61B1/043; A61B1/06; A61B1/07; G01N2021/6417; G01N2021/6484; G01N21/6456; G01N21/6458
Claims Analysis
Total Claims: 56
Claim 1
Independent Claim
146 words
A method of detecting disease within a particular tissue of a plant or animal comprising the steps of: activating the particular plant or animal tissue by application of radiation through at least one optical fiber under conditions effective to promote a simultaneous multiphoton excitation of the particular plant or animal tissue and to emit an intrinsic fluorescence characteristic, wherein said at least one optical fiber has a distal end provided with a terminal focusing lens; comparing the intrinsic fluorescence characteristic to fluorescence emitted by exciting healthy tissue of the particular plant or animal under the same conditions used to carry out said activating; and identifying the particular tissue of a plant or animal where the intrinsic fluorescence characteristic differs from the fluorescence, emitted by exciting healthy tissue of the particular plant or animal under the same conditions used to carry out said activating, as potentially diseased.
Claim 2
Independent Claim
146 words
A method of detecting disease within a particular tissue of a plant or animal comprising the steps of: activating the particular plant or animal tissue by application of radiation through at least one optical fiber under conditions effective to promote a simultaneous multiphoton excitation of the particular plant or animal tissue and to emit an intrinsic fluorescence characteristic, wherein said at least one optical fiber has a distal end provided with a terminal focusing lens; comparing the intrinsic fluorescence characteristic to fluorescence emitted by exciting healthy tissue of the particular plant or animal under the same conditions used to carry out said activating; and identifying the particular tissue of a plant or animal where the intrinsic fluorescence characteristic differs from the fluorescence, emitted by exciting healthy tissue of the particular plant or animal under the same conditions used to carry out said activating, as potentially diseased.
Claim 3
Dependent Claim
21 words
The method according to claim 1 , wherein the radiation is applied substantially adjacent to the particular plant or animal tissue.
Claim 4
Dependent Claim
19 words
The method according to claim 1 , wherein the radiation is applied within the particular plant or animal tissue.
Claim 5
Dependent Claim
25 words
The method according to claim 1 further comprising: treating the particular plant or animal tissue with at least one photo-active agent prior to said activating.
Claim 6
Dependent Claim
15 words
The method according to claim 1 , wherein the radiation is generated by a laser.
Claim 7
Dependent Claim
12 words
The method according to claim 5 , wherein the radiation is pulsed.
Claim 8
Dependent Claim
25 words
The method according to claim 6 , wherein the radiation is pulsed at a pulse width between about 10 −9 second to 10 −15 second.
Claim 9
Dependent Claim
14 words
The method according to claim 7 , wherein the laser is a mode-locked laser.
Claim 10
Dependent Claim
27 words
The method according to claim 1 , wherein the distal end of the at least one optical fiber abuts a surface of the plant or animal tissue.
Claim 11
Dependent Claim
22 words
The method according to claim 1 , wherein the at least one optical fiber is disposed within the plant or animal tissue.
Claim 12
Dependent Claim
23 words
The method according to claim 10 , wherein the at least one optical fiber constitutes or is associated with an optical biopsy needle.
Claim 13
Dependent Claim
25 words
The method according to claim 1 , wherein the at least one optical fiber is disposed within a body cavity of the plant or animal.
Claim 14
Dependent Claim
19 words
The method according to claim 12 , wherein the at least one optical fiber is associated with an endoscope.
Claim 15
Dependent Claim
29 words
The method according to claim 12 , wherein the body cavity is selected from the group consisting of colon, esophagus, stomach, intestine, bladder, uterus, vagina, lung, ovaries, and throat.
Claim 16
Dependent Claim
24 words
The method according to claim 1 further comprising: collecting radiation applied to the plant or animal tissue using one or more collection optical fibers.
Claim 17
Dependent Claim
20 words
A method according to claim 1 , wherein the tissue is effective to produce second or third harmonics of illumination.
Claim 18
Independent Claim
94 words
A method of producing an image of an internal region of a particular tissue within a plant or animal comprising the steps of: activating the particular plant or animal tissue with radiation applied through at least one optical fiber under conditions effective to promote a simultaneous multiphoton excitation of the internal region of the particular tissue within the plant or animal and produce an autofluorescence and collecting the autofluorescence to produce an image of the internal region, wherein said at least one optical fiber has a distal end provided with a terminal focusing lens.
Claim 19
Independent Claim
94 words
A method of producing an image of an internal region of a particular tissue within a plant or animal comprising the steps of: activating the particular plant or animal tissue with radiation applied through at least one optical fiber under conditions effective to promote a simultaneous multiphoton excitation of the internal region of the particular tissue within the plant or animal and produce an autofluorescence and collecting the autofluorescence to produce an image of the internal region, wherein said at least one optical fiber has a distal end provided with a terminal focusing lens.
Claim 20
Dependent Claim
25 words
The method according to claim 17 , wherein the at least one optical fiber is juxtaposed with a surface of the plant or animal tissue.
Claim 21
Dependent Claim
25 words
The method according to claim 17 further comprising: treating the particular plant or animal tissue with at least one photo-active agent prior to said activating.
Claim 22
Dependent Claim
15 words
The method according to claim 17 , wherein the radiation is generated by a laser.
Claim 23
Dependent Claim
12 words
The method according to claim 17 , wherein the radiation is pulsed.
Claim 24
Dependent Claim
25 words
The method according to claim 21 , wherein the radiation is pulsed at a pulse width between about 10 −12 second to 10 −15 second.
Claim 25
Dependent Claim
14 words
The method according to claim 21 , wherein the laser is a mode-locked laser.
Claim 26
Dependent Claim
25 words
The method according to claim 17 , wherein the at least one optical fiber is disposed within a body cavity of the plant or animal.
Claim 27
Dependent Claim
19 words
The method according to claim 17 , wherein the at least one optical fiber is associated with an endoscope.
Claim 28
Dependent Claim
29 words
The method according to claim 17 , wherein the body cavity is selected from the group consisting of colon, esophagus, stomach, intestine, bladder, uterus, vagina, lung, ovaries, and throat.
Claim 29
Dependent Claim
20 words
The method according to claim 17 , wherein the at least one optical fiber is a bundle of optical fibers.
Claim 30
Dependent Claim
20 words
A method according to claim 17 , wherein the tissue is effective to produce second and third harmonics of illumination.
Claim 31
Independent Claim
84 words
A method of detecting and localizing fluorescence within a subject comprising the steps of: applying radiation to an internal surface of the subject through at least one optical fiber, each of which has a distal end provided with a terminal focusing lens which terminates in a tip proximate to the internal surface, under conditions effective to cause simultaneous multiphoton absorption of fluorophore molecules within the internal surface and, as a result, fluorescent excitation proximate to the tip of the at least one optical fiber.
Claim 32
Independent Claim
84 words
A method of detecting and localizing fluorescence within a subject comprising the steps of: applying radiation to an internal surface of the subject through at least one optical fiber, each of which has a distal end provided with a terminal focusing lens which terminates in a tip proximate to the internal surface, under conditions effective to cause simultaneous multiphoton absorption of fluorophore molecules within the internal surface and, as a result, fluorescent excitation proximate to the tip of the at least one optical fiber.
Claim 33
Dependent Claim
28 words
A method according to claim 29 , wherein the at least one optical fiber is inserted into the subject through an externally accessible body cavity of the subject.
Claim 34
Dependent Claim
19 words
A method according to claim 30 , wherein the at least one optical fiber is associated with an endoscope.
Claim 35
Dependent Claim
29 words
A method according to claim 30 , wherein the body cavity is selected from the group consisting of colon, esophagus, stomach, intestine, bladder, uterus, vagina, lung, ovaries, and throat.
Claim 36
Dependent Claim
26 words
A method according to claim 29 , wherein the at least one optical fiber is inserted into the subject through a penetrable surface of the body.
Claim 37
Dependent Claim
18 words
A method according to claim 29 further comprising: imaging the internal surface of the subject after said subjecting.
Claim 38
Dependent Claim
20 words
A method according to claim 29 further comprising: detecting disease in the internal surface of the subject after said applying.
Claim 39
Dependent Claim
21 words
A method according to claim 29 further comprising: treating the subject with at least one photo-active agent prior to said applying.
Claim 40
Dependent Claim
15 words
A method according to claim 29 , wherein the radiation is generated with a laser.
Claim 41
Dependent Claim
12 words
A method according to claim 29 , wherein the radiation is pulsed.
Claim 42
Dependent Claim
25 words
A method according to claim 38 , wherein the radiation is pulsed at a pulse width between about 10 −12 second to 10 −15 second.
Claim 43
Dependent Claim
14 words
A method according to claim 39 , wherein the laser is a mode-locked laser.
Claim 44
Dependent Claim
28 words
A method according to claim 29 further comprising: detecting histological and clinical composition, structure, metabolic state, and vitality in the internal surface of the subject after said applying.
Claim 45
Dependent Claim
29 words
A method according to claim 29 further comprising: detecting functional response to physiological and pharmacological stimuli and disease states in the internal surface of the subject after said applying.
Claim 46
Dependent Claim
33 words
A method according to claim 29 further comprising: detecting tissue or drug fluorescence excitation and emission spectra, luminosity, fluorescence lifetime, and temporal fluctuations in the internal surface of the subject after said applying.
Claim 47
Dependent Claim
20 words
A method according to claim 29 , wherein the tissue is effective to produce second and third harmonics of illumination.
Claim 48
Independent Claim
90 words
A method of detecting and localizing fluorescence within a body of penetrable material comprising the steps of: applying radiation to an internal region of the body of penetrable material through at least one optical fiber, each of which has a distal end provided with a terminal focusing lens which terminates in a tip proximate to the internal region, under conditions effective to cause simultaneous multiphoton absorption of fluorophore molecules within the internal region and, as a result, fluorescent excitation proximate to the tip of the at least one optical fiber.
Claim 49
Independent Claim
90 words
A method of detecting and localizing fluorescence within a body of penetrable material comprising the steps of: applying radiation to an internal region of the body of penetrable material through at least one optical fiber, each of which has a distal end provided with a terminal focusing lens which terminates in a tip proximate to the internal region, under conditions effective to cause simultaneous multiphoton absorption of fluorophore molecules within the internal region and, as a result, fluorescent excitation proximate to the tip of the at least one optical fiber.
Claim 50
Dependent Claim
22 words
A method according to claim 45 , wherein the at least one optical fiber is inserted into the body of penetrable material.
Claim 51
Dependent Claim
17 words
A method according to claim 45 further comprising: imaging the region of the subject after said subjecting.
Claim 52
Dependent Claim
15 words
A method according to claim 45 , wherein the radiation is generated with a laser.
Claim 53
Dependent Claim
12 words
A method according to claim 45 , wherein the radiation is pulsed.
Claim 54
Dependent Claim
25 words
A method according to claim 49 , wherein the radiation is pulsed at a pulse width between about 10 −12 second to 10 −15 second.
Claim 55
Dependent Claim
14 words
A method according to claim 50 , wherein the laser is a mode-locked laser.
Claim 56
Dependent Claim
23 words
A method according to claim 45 , wherein the body of penetrable material is effective to produce second and third harmonics of illumination.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2008-01-04 | 2008-07-05 | 2009-01-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2012-01-04 | 2012-07-05 | 2013-01-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2016-01-04 | 2016-07-05 | 2017-01-04 | $7700.00 | Window Closed / Lapsed |