WO2003010561A2 - Optical coupler for measuring tissue fluorescence - Google Patents
Optical coupler for measuring tissue fluorescence Download PDFInfo
- Publication number
- WO2003010561A2 WO2003010561A2 PCT/US2002/023412 US0223412W WO03010561A2 WO 2003010561 A2 WO2003010561 A2 WO 2003010561A2 US 0223412 W US0223412 W US 0223412W WO 03010561 A2 WO03010561 A2 WO 03010561A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tissue
- coupling device
- optical coupling
- light
- mirror
- Prior art date
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- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
Definitions
- the present invention overcomes the problems and disadvantages associated with current strategies and designs, and provides new devices, systems, and methods for efficiently optically coupling an area of tissue with a light source and spectroscope, probe, or any type of device used for the measurement of optical properties of tissue, e.g. skin.
- the invention provides, a spectroscopic system comprising an optical coupling device; a plurality of fiber optic cables, and a spectrometer, wherein the plurality of fiber optic cables connect the optical coupling device to the spectrometer and are provided to transmit light comprising excitation radiation from a radiation source to the tissue and radiation comprising fluorescence away from the tissue.
- a pump is provided to increase, decrease, or stabilize the pressure of the volume within the optical coupling device.
- the invention provides, a method comprising the steps of placing an optical coupling device in close proximity to a tissue; decreasing, increasing, or stabilizing the pressure within the optical coupling device; exposing tissue to radiation from a source; and collecting fluorescent light emitted by said tissue.
- the invention provides, emission light at the excitation or absorption wavelength(s) is collected in addition to fluorescence light.
- this device can be also be used to make absorption measurements insofar as the light emitted is the same wavelength as the excitation light or absorption measurements in other regions.
- the instant invention provides distinct advantages over existing devices, systems and methods of collecting spectral data from tissue.
- One such advantage of the invention is that leakage of excitation light into detection optics is eliminated.
- Another advantage of this invention is that interference from outside electromagnetic radiation is minimized, if not entirely eliminated.
- Another advantage is that this invention provides accurate measurements of physiological properties by applying a consistent pressure to the skin over time.
- Another advantage of this invention is the ability to stretch or smooth the skin by changing the pressure applied to the skin, thereby minimizing air gaps that can cause scattering of excitation light.
- Another advantage of this invention is that it better integrates the emission and excitation light over a skin area large in comparison to typical spatial heterogeneities thereby reducing signal variance across sites.
- Figure 2 An optical coupling device having three mirrors (Ml , M2, M3) and three detection options (Dl, D2, D3).
- Figure 3 An optical coupling device having four detection options (D 1 , D2, D3 ,
- Figure 4 An optical coupling device directed to exciting glucose and osmolyte sensors in near UV and NLR.
- FIG. 5 An optical coupling device have four detector options (Dl, D2, D3, D4), disposed at a diaphragm or skin surface.
- Figure 6 An optical coupling device wherein a transparent membrane is eliminated.
- the present invention comprises devices, systems and methods for optically coupling tissue to a spectroscope.
- the invention is directed to an optical coupler that can be used on skin and other tissues.
- FIG. 1 A preferred embodiment of the invention is depicted in Figure 1, wherein an optical coupling device according to an embodiment of the invention is shown.
- the device comprises a curved reflector having a cross-sectional shape of a cardioid.
- alternative cross-sectional and three-dimensional shapes include, but are not limited to, an ellipse, circular structure, oval, sphere, triangle, rectangle, dome structure such as a geodesic dome, or other suitable shapes.
- this reflector At the focus of this reflector is disposed a detector on top of a small curved mirror. This mirror is fixed on top of a transparent membrane sealed to the curved reflector.
- the membrane is flexible and most preferably, elastic.
- the membrane which may comprise a means for performing a calibration methodology, can be permanent or alternatively, inexpensively mass-produced and thereby, disposable.
- the curved reflector is rigid and has a fluid port disposed thereon.
- a second opening is provided to allow the transmission of excitation light from a source and emission light collected from the detector without compromising the seal of the fluid, e.g., air, inside the curved reflector, h a preferred embodiment, the second opening is at the top of the curved reflector, however, in other embodiments the opening maybe disposed at other locations.
- the fluid e.g., air
- the device is placed on top of a tissue, such as skin, and the pressure inside the reflector can be reduced causing the membrane to be drawn into the reflector, pulling the skin upwards.
- a pressure reduction causes the skin surface to convexly deform, as shown in Figure 1.
- the pressure differential is not sufficient to induce discomfort, significant physiological sequellae, or intentional change.
- the pressure inside can be increased to concavely deform the skin surface. As noted above, this preferably occurs without discomfort, intentional change, or manifest physiological consequence.
- the device may be positioned on any desired location of a patient.
- the device may be positioned on skin such as on a forearm or leg, fingernails, earlobes, lips or internal tissues for example during an invasive surgical procedure.
- the device is placed on an arm or leg of a patient.
- the patient is generally a mammal such as a dog or cat, and preferably is a human.
- the instant invention is applicable to testing other tissues in vitro.
- the exposure to the excitation light is minimal.
- the exposure time is less than a minute, preferably less than 15 seconds, and more preferably less than 5 seconds.
- two or more tissue areas are examined with the device and emission data averaged, thereby reducing heterogeneity effects, to acquire a more accurate measurement. Further, sampling may be taken over a wide area for normalization purposes. In this manner, changes associated with convex and/or concave deformations can be minimized or completely eliminated. Anomalous measurements maybe removed prior to averaging using commonly known techniques (M.S. Srivastava Methods of Multivariate Statistics, Wiley, 2002).
- FIG. 6 Another preferred embodiment is shown in Figure 6, wherein the membrane is eliminated and the combination of detector and curved mirror is disposed in either direct contact or close proximity with the skin.
- the detector and curved mirror may be connected to curved reflector by a wire grid, which would permit free passage of radiation, or may be connected directly to the inside wall of the curved reflector.
- compositions useful as interface media for facilitating contact between a skin surface and the curved reflector may be used for optically coupling, standardizing, and/or improving contact between the skin surface and curved reflector with or without the membrane.
- the surfaces of these locations may be prepared prior to excitation to enhance the study of the physiology of the sample.
- lotions for hydrating tissue, optical gels, pharmaceuticals, desiccants, disinfectants, or blood vessel treatments may be used.
- Such an arrangement is particularly suited for collecting fluorescence, absorbance or other spectral information from the skin using the embodiments of the present invention. See also U.S. Patent Application No. 09/704,421, entitled “Interface Medium for Tissue Surface Probe," filed November 3, 2000, which is herein incorporated by reference in its entirety.
- the source and the detector may be discrete devices or they may consist of optical fibers that may be independently connected to a light source and a spectrometer.
- the source excites tissue at a first wavelength or first range of wavelengths. Further, the source may be disposed at any location within the device.
- the detector collects light emitted from the tissue, due to fluorescence, absorption, or scatter of tissue components, at a second wavelength or second range of wavelengths either equal to, overlapping, or entirely different from the first wavelength or range of wavelengths. Particularly in fluorescence of biological molecules, emission wavelengths are longer than the excitation wavelength due to non-radiative transfer of energy to the molecular vibrational and rotational states.
- a plurality of sources and/or detectors may be employed.
- multiple sources and detectors can be placed at different angles within the device to take advantage of various wavelengths of light via their reflection at varying angles.
- one or more detectors may be used to acquire depth-resolved spectral information from the tissue.
- the present invention effectively couples excitation radiation from a source onto a tissue surface, such as skin, and the emission light from said tissue surface, such as the skin, to a detector.
- the collection of said emissions is improved by virtue of the curved reflector, which focuses said emitted light onto a detector.
- Excitation is similarly improved insofar as the cardioid mirror facilitates uniform tissue illumination.
- the device also has the potential to be used with wavelength or temporally resolved spectral data.
- uniform illumination of the tissue surfaces and collection of spectral data is achieved by careful matching of the optical properties of the fiber, the mirror, and the curvature of the reflector. Particularly, light emitted from the skin will impact the reflector surface, which will then focus said emissions onto a detector. If a fiber is used as the detector then the end can be terminated in a sphere. The sphere is placed at the focus of the reflector, and the light is collected over a large solid angle.
- cardioid mirror M 2 is connected to a transparent diaphragm and placed on a tissue surface, e.g., arm, either with or without a coupling substance interposed between the diaphragm and the skin.
- a coupling substance can enhance both the transfer of light and the collection of light such as fluorescent spectra, from the tissue to the probe.
- a liquid, cement (adhesive), or gel with an index of refraction that closely approximates that of an optical fiber, and is used to reduce specula reflection at the fiber end face
- coupling substances herein may be used to match refractive indices of the skin surface and the diaphragm.
- the substance would be preferably water soluble, non-toxic, and pH buffered.
- the substance may also contain known fiuorophores and/or chromophores that can support calibration efforts.
- the volume enclosed by either the cardioid mirror and diaphragm, the diaphragm and tissue surface, or both, may be evacuated by a pump operating through an opening in the cardioid mirror. Said enclosed volume may hold air or a coupling substance, as described above.
- Excitation light enters a small hole in the cardioid mirror at point S, and is reflected by mirror M 1 illuminating the surface of the cardioid to produce rays, which enter the tissue at oblique angles and illuminate, by photon diffusion, object Z.
- targets within the tissue e.g. structural or matrix components such as mitochondria or collagen fibers, are excited by the excitation energy.
- the tissue absorbs, emits, and scatters light, some of which will reenter the cardioid by traversing a reverse course whereupon it will be focused on mirror M ⁇ and returned to the source position S.
- the longer wavelength fluorescence is readily separated from the incident excitation by mirror M 3 , which may be dichroic or silvered, or any other means that reflects a particular band of spectral energy and transmits all others, and collected at detector D 3 .
- mirror M 3 which may be dichroic or silvered, or any other means that reflects a particular band of spectral energy and transmits all others, and collected at detector D 3 .
- the device fully exploits the inherent optical reciprocity of the cardioid system.
- a further advantage is conferred through the provision of multiple pathway illumination and secondarily collecting the spectral emissions for analysis. Scattered light may be acquired over the large solid angle created by the geometry of the device, thereby providing additional data for analysis.
- the first source emits radiation at 366 nm and the second source emits radiation at 800 nm. Further, detectors D 3 and D 4 collect radiation at 460 and 800 nm, respectively.
- tryptophan which fluoresces in the 295-350 nanometer (nm) region
- keratin which fluoresces in the 295-340 nm region
- NADH nicotinamide adenine dinucleotide
- FAD flavin adenine dinucleotide
- fluorophores associated with collagen cross-links which fluoresce in a broad region from 420 to 490 nm.
- an optical coupling device according to an alternative embodiment is directed to exciting glucose and osmolyte sensors.
- An osmolyte sensor determines osmotic strength on the basis of the numbers of particles suspended in a given solution.
- source S 2 along with the distal ends of fiber optic cable, are connected to detectors D 3 and D , such that they are disposed along the diaphragm.
- illuminating a tissue with excitation comprises exciting a target within said tissue.
- the target may be a structural, cellular, matrix, or molecular species in a patient.
- the target comprises pepsin- or collagenase-digestible collagen cross links, non-pepsin digestible collagen cross links, tryptophan, elastin, elastin cross-links, keratin, serum proteins, Glu-T proteins, NADH, NADPH, flavoproteins (e.g. FAD), melanin precursors, porphyrins (e.g.
- hemoglobin including hemoglobin, glycosylated hemoglobin Ale, or red blood cells
- cytochromes including hemoglobin, glycosylated hemoglobin Ale, or red blood cells
- cytochromes including hemoglobin, glycosylated hemoglobin Ale, or red blood cells
- cytochromes including hemoglobin, glycosylated hemoglobin Ale, or red blood cells
- carotenoid including salicylate (aspirin), lactate, pyruvate, ketones (e.g. acetoacetate and beta-hydroxybutyrate), free fatty acids, succinate, fumarate, dihydroxyacetone phosphate (DHAP), 3- phosphoglycerate, acetyl CoA, succinyl CoA, alpha-ketoglutarate, malate, citrate, isocitrate, bicarbonate, insulin, triglyceride, cholesterol, phosphorus, calcium, blood urea, electrolytes, bilirubin, creatinine, albumin, lactate
- a convenient way to describe the diffuse reflected spectrum is to take the logarithm of the ratio the signal to the incident spectrum. In transmission absorption spectroscopy, this is routinely done to provide estimates of concentrations of absorbers in the medium when Beer-Lambert's law is know to apply. Although Beer-Lambert's law does not apply in tissue reflectance studies, it is none-the-less a useful transformation. The resulting "absorbance" spectrum contains features that may be useful in identifying constituent components.
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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AU2002322606A AU2002322606A1 (en) | 2001-07-25 | 2002-07-24 | Optical coupler for measuring tissue fluorescence |
Applications Claiming Priority (2)
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US30736801P | 2001-07-25 | 2001-07-25 | |
US60/307,368 | 2001-07-25 |
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WO2003010561A2 true WO2003010561A2 (en) | 2003-02-06 |
WO2003010561A3 WO2003010561A3 (en) | 2003-06-19 |
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PCT/US2002/023412 WO2003010561A2 (en) | 2001-07-25 | 2002-07-24 | Optical coupler for measuring tissue fluorescence |
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AU (1) | AU2002322606A1 (en) |
WO (1) | WO2003010561A2 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011150919A3 (en) * | 2010-06-01 | 2012-04-19 | Mfd Diagnostics Gmbh | Optical probe having a probe head and probe ferrule |
US9782096B2 (en) | 2011-01-31 | 2017-10-10 | Clothing Plus Mbu Oy | Textile substrate for measuring physical quantity |
US11291409B2 (en) | 2014-12-03 | 2022-04-05 | Clothing Plus Mbu Oy | Device for determining effects of aging of a wearable device |
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US5741213A (en) * | 1995-10-25 | 1998-04-21 | Toa Medical Electronics Co., Ltd. | Apparatus for analyzing blood |
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US6167290A (en) * | 1999-02-03 | 2000-12-26 | Bayspec, Inc. | Method and apparatus of non-invasive measurement of human/animal blood glucose and other metabolites |
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2002
- 2002-07-24 WO PCT/US2002/023412 patent/WO2003010561A2/en not_active Application Discontinuation
- 2002-07-24 AU AU2002322606A patent/AU2002322606A1/en not_active Abandoned
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US4622974A (en) * | 1984-03-07 | 1986-11-18 | University Of Tennessee Research Corporation | Apparatus and method for in-vivo measurements of chemical concentrations |
US4681442A (en) * | 1984-05-14 | 1987-07-21 | International Business Machines Corporation | Method for surface testing |
US5741213A (en) * | 1995-10-25 | 1998-04-21 | Toa Medical Electronics Co., Ltd. | Apparatus for analyzing blood |
US5846513A (en) * | 1997-07-08 | 1998-12-08 | Carewise Medical Products Corporation | Tumor localization and removal system using penetratable detection probe and removal instrument |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011150919A3 (en) * | 2010-06-01 | 2012-04-19 | Mfd Diagnostics Gmbh | Optical probe having a probe head and probe ferrule |
US9782096B2 (en) | 2011-01-31 | 2017-10-10 | Clothing Plus Mbu Oy | Textile substrate for measuring physical quantity |
US10610118B2 (en) | 2011-01-31 | 2020-04-07 | Clothing Plus Mbu Oy | Textile substrate for measuring physical quantity |
US11291409B2 (en) | 2014-12-03 | 2022-04-05 | Clothing Plus Mbu Oy | Device for determining effects of aging of a wearable device |
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AU2002322606A1 (en) | 2003-02-17 |
WO2003010561A3 (en) | 2003-06-19 |
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