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WO2003010561A2 - Coupleur optique destine a mesurer la fluorescence des tissus - Google Patents

Coupleur optique destine a mesurer la fluorescence des tissus Download PDF

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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
Application number
PCT/US2002/023412
Other languages
English (en)
Other versions
WO2003010561A3 (fr
Inventor
Robert G. Messerschmidt
Jim Childs
Pierre Trepagnier
James Mansfield
Jenny E. Freeman
Sean Toy
Britton Chance
Original Assignee
Argose, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Argose, Inc. filed Critical Argose, Inc.
Priority to AU2002322606A priority Critical patent/AU2002322606A1/en
Publication of WO2003010561A2 publication Critical patent/WO2003010561A2/fr
Publication of WO2003010561A3 publication Critical patent/WO2003010561A3/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/683—Means for maintaining contact with the body
    • A61B5/6834—Means for maintaining contact with the body using vacuum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/14—Coupling media or elements to improve sensor contact with skin or tissue
    • A61B2562/146—Coupling media or elements to improve sensor contact with skin or tissue for optical coupling
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • 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.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Biophysics (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Optics & Photonics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Emergency Medicine (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

L'invention concerne un dispositif destiné à coupler optiquement de manière efficace des tissus à un spectroscope. Le coupleur optique comprend, de préférence, une enveloppe partielle et rigide comportant une paroi intérieure qui réfléchit le rayonnement électromagnétique, une ouverture sur l'enveloppe destinée au passage de la lumière et un ou plusieurs miroirs, ainsi que des paires de détecteurs de lumière. Le coupleur peut consister en un composant d'un système spectroscopique de tissu comprenant un ou plusieurs coupleurs, un spectroscope, et un milieu d'interface, un détecteur ainsi qu'une source de lumière. Le procédé de l'invention permet la détection de propriétés optiques d'un tissu et, de préférence, de la peau.
PCT/US2002/023412 2001-07-25 2002-07-24 Coupleur optique destine a mesurer la fluorescence des tissus WO2003010561A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002322606A AU2002322606A1 (en) 2001-07-25 2002-07-24 Optical coupler for measuring tissue fluorescence

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US30736801P 2001-07-25 2001-07-25
US60/307,368 2001-07-25

Publications (2)

Publication Number Publication Date
WO2003010561A2 true WO2003010561A2 (fr) 2003-02-06
WO2003010561A3 WO2003010561A3 (fr) 2003-06-19

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PCT/US2002/023412 WO2003010561A2 (fr) 2001-07-25 2002-07-24 Coupleur optique destine a mesurer la fluorescence des tissus

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AU (1) AU2002322606A1 (fr)
WO (1) WO2003010561A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011150919A3 (fr) * 2010-06-01 2012-04-19 Mfd Diagnostics Gmbh Sonde optique pourvue d'une tête de sonde et d'une virole de sonde
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
CN116297278A (zh) * 2023-02-23 2023-06-23 广西电网有限责任公司电力科学研究院 一种六氟化硫分解组分检测装置及方法
US12442786B2 (en) 2021-10-14 2025-10-14 Medtronic Minimed, Inc. Sensors for 3-hydroxybutyrate detection

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4622974A (en) * 1984-03-07 1986-11-18 University Of Tennessee Research Corporation Apparatus and method for in-vivo measurements of chemical concentrations
EP0162120B1 (fr) * 1984-05-14 1988-12-07 Ibm Deutschland Gmbh Procédé et dispositif pour le contrôle de surface
US5741213A (en) * 1995-10-25 1998-04-21 Toa Medical Electronics Co., Ltd. Apparatus for analyzing blood
US5846513B1 (en) * 1997-07-08 2000-11-28 Carewise Medical Products Corp Tumor localization and removal system using penetratable detection probe and removal instrument
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

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011150919A3 (fr) * 2010-06-01 2012-04-19 Mfd Diagnostics Gmbh Sonde optique pourvue d'une tête de sonde et d'une virole de sonde
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
US12442786B2 (en) 2021-10-14 2025-10-14 Medtronic Minimed, Inc. Sensors for 3-hydroxybutyrate detection
CN116297278A (zh) * 2023-02-23 2023-06-23 广西电网有限责任公司电力科学研究院 一种六氟化硫分解组分检测装置及方法

Also Published As

Publication number Publication date
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AU2002322606A1 (en) 2003-02-17

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