WO2023161965A1 - Sonde optoélectronique pour l'analyse de tissus situés a l'intérieur du corps humain - Google Patents

Sonde optoélectronique pour l'analyse de tissus situés a l'intérieur du corps humain Download PDF

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Publication number
WO2023161965A1
WO2023161965A1 PCT/IT2022/000011 IT2022000011W WO2023161965A1 WO 2023161965 A1 WO2023161965 A1 WO 2023161965A1 IT 2022000011 W IT2022000011 W IT 2022000011W WO 2023161965 A1 WO2023161965 A1 WO 2023161965A1
Authority
WO
WIPO (PCT)
Prior art keywords
tissue
fibre
channel
sleeve
probe according
Prior art date
Application number
PCT/IT2022/000011
Other languages
English (en)
Inventor
Cosimo GENTILE
Carmen MIANO
Donatella VECCHIONE
Marco Pisco
Francesco Bruno
Andrea Cusano
Antonello Cutolo
Sara SPAZIANI
Original Assignee
Teoresi S.P.A.
Centro Regionale Information Communication Technology Scrl
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 Teoresi S.P.A., Centro Regionale Information Communication Technology Scrl filed Critical Teoresi S.P.A.
Priority to PCT/IT2022/000011 priority Critical patent/WO2023161965A1/fr
Publication of WO2023161965A1 publication Critical patent/WO2023161965A1/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
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • 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
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • 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
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6852—Catheters
    • A61B5/6853—Catheters with a balloon

Definitions

  • the present invention relates to an optoelectronic probe for the analysis of tissues located inside the human body .
  • Document US5615673A discloses a method for measuring the concentration of a gas (oxygen or carbon dioxide) dissolved in blood comprising the steps of : irradiating the blood with laser radiation having a wavelength such that Raman scattering occurs for such gas; collecting Raman scattered light from the dissolved gas; and detecting the Raman scattered light collected from the dissolved gas in response to the laser radiation .
  • Document W02010083484A2 discloses a Raman spectrographic system for measuring Raman spectra of a tissue, the system comprises : a Raman spectrographic probe having an elongated handle extending from a first end to a second end and a contact tip extending over a predefined distance from the first end; a Raman spectrograph including a detector; a first laser source adapted to produce a first laser radiation at a predefined first wavelength; a first excitation fibre coupled to the laser source and extending as far as the first end of the Raman spectrographic probe and adapted to transfer the laser radiation to the first end; a plurality of emission fibres coupled to the Raman spectrograph and extending as far as the first end of the probe of the Raman spectrograph.
  • the system of W02010083484A2 can be used by a technician or a physician to detect a pathologic tissue by placing the tip of the probe toward the tissue to be examined.
  • This system only allows a superficial analysis of the tissue and does not allow the access to portions of a tissue located inside the human body and belonging to an internal organ (e . g . liver, kidney, etc . ) .
  • Aim of the present invention is to realize a probe capable of examining tissues located inside the human body allowing the identification of the type of cells of the tissue in which the probe is inserted .
  • this probe is able to detect structural differences in tissue composition .
  • the probe of the present invention can be used, for example, to identify a variety of type of tumour pathologies by providing a rapid diagnosis .
  • Figure 1 shows in perspective view an optoelectronic probe realized according to the dictates of the present invention
  • Figure 2 shows a longitudinal section of the probe realized according to the plane indicated in Figure 1 and arranged in a first operating position
  • Figure 3 shows a longitudinal section of the probe realized according to the plane indicated in Figure 1 and arranged in a second operating position
  • Figure 4 shows a longitudinal section of the probe realized according to the plane indicated in Figure 1 and arranged in a third operating position
  • Figure 5 schematically shows a system using the probe realized according to the present invention .
  • number 1 denotes an optoelectronic probe for the analysis of tissues realized according to the present invention .
  • the probe 1 comprises a flexible external tubular protection element 2 (bundle) provided with a front end portion 3 configured to be inserted into a fabric 4 (see Figure 4 ) to be subjected to analysis and provided with a rear portion which is connected with a handling system 5 of known type and formed by parts available on the market (such as stepper motors, e . g . schematically and partially represented in Figure 1 ) adapted to achieve the axial movement of the tubular element 2 with opposite directions (see arrows F
  • the tubular element 2 typically has a circular cross-section with an external diameter ranging from 0. 908 mm to 2 .769 mm, an internal diameter ranging from 0. 603 mm to 2. 159 mm, a thickness ranging from 0.152 mm to 0.305 mm and can be made of stainless steel or other medical material .
  • the probe 1 further comprises an internal sleeve 6 axially sliding inside the tubular protection element 2 with opposite directions under the thrust of the handling system 5 and provided with a front end portion 6-a whose position with respect to the front end portion 3 of the tubular element 2 is adjustable .
  • the front end portion 6-a may be contained - in a rest position shown in Figures 2 and 3 - inside the tubular protection element 2 or can at least partially project - in a position of use shown in Figure 4 from the tubular element 2.
  • the internal sleeve 6 typically has a circular cross-section with an outside diameter ranging between 0. 603 mm and 2. 159 mm and can be made of medical grade Polytetrafluoroethylene (PTFE) or generally in plastic material with medical specifications .
  • PTFE Polytetrafluoroethylene
  • the internal sleeve 6 has a series of axially extending channels including : a first channel 7 housing a first emission optical fibre 8 having a front end 8-a ( Figures 2 and 3) configured to supply an excitation signal to the tissue 4 and a rear end 8-b ( Figure 5) configured to receive in input the excitation signal produced by an optical signal generator 9 ( Figure 5) conveniently, the optical signal generator 9 is a solid-state laser usable for Raman spectroscopy and adapted to generate a wavelength signal of 532 nm,
  • a second channel 11 housing a second collection optical fibre
  • a Raman spectrometer 13 Figure 5
  • a third channel 15 extending over the entire length of the sleeve 6 and configured to feed a nano-particle-containing fluid into the tissue 4 -
  • the dimensions of the third channel 15 may be in the order of 50 T 200pm;
  • a fourth channel 17 extends over the entire length of the sleeve
  • an expandable element 18 configured to project from the end 6-a of the sleeve 6 when it is arranged in the rest position to expand and be arranged in contact with the internal walls of the external tubular protection element 2 ( Figure 2 ) acting as a plug and separating the end 6-a of the sleeve 6 from the tissue 4 .
  • the function of the expandable element 18 is to protect the optical fibres 8 and 12 from contamination until the arrival of the protection element 2 at the site where the measurement is to be carried out . When this position is reached, the expandable element
  • the expandable element 18 is of the balloon type and is realized using known technologies .
  • first, second, third channel 7 , 11, 15 and the fourth channel 17 have a circular cross-section .
  • the internal sleeve 6 can in fact be configured to house N emission fibres and M collection fibres . More third channels 15 could also be provided for the fluid.
  • the optical fibres 8 and 12 may have a core preferably consisting of molten silicon or sapphire to reduce the fluorescent background .
  • the choice of the optical fibres 8 and 12 does not in any way limit the invention .
  • Different diameters and numerical apertures can be used to improve collection efficiency .
  • multimodal fibres with the pure silicon core and the hard polymer coating, a transmission region ranging from 400 T 2200 nm, a core with a diameter of 200 ⁇ 5 pm, a coating with a diameter of 225 ⁇ 5 pm and a numerical aperture (NA) of 0.50 can be used .
  • the third channel 15 is conveniently connected with a pressurised fluid delivery system 20 ( Figure 5) such as a peristaltic pump or a pressurization system, both of known type .
  • a pressurised fluid delivery system 20 such as a peristaltic pump or a pressurization system, both of known type .
  • the fluid carries a plurality of nanoparticles in suspension; the nanoparticles used for this application typically consist of a plasmonic biocompatible material (e . g . , gold, silver, copper, etc . ) that is of inert type and therefore usable in clinical applications .
  • a plasmonic biocompatible material e . g . , gold, silver, copper, etc .
  • the particles have nanometric dimensions (preferably in the range 10 -r 100 nm) so as to create hotspots directly on the tissue 4 to be analysed, and have different geometries : spheres, sticks, triangles, hexagons, prisms, spirals, cubes, threads, and stars .
  • the particles are functionalised, i . e . a specific molecule (e . g . antibody, aptamer, peptide) is covalently bound to the surface of the nanoparticle .
  • the molecule is a Raman reporter so defined because it has a specific Raman imprint when illuminated by the excitation laser .
  • the Raman reporter performs a dual function : the tracking of the Raman signal and the possibility of engaging a recognition element capable of selectively and specifically recognizing a biomarker present on the cell membrane .
  • the nanoparticles are closely related to the use of the Raman
  • the probe 1 is however also usable without the use of such microparticles in a classical Raman technology .
  • the front end 8-a of the first emission fibre 8 may be provided with a narrow-band band-pass filter (not shown) formed by a layered structure integrated into the fibre and formed by layers having different thickness and different refractive index so as to realize a phase-shifted Bragg grating .
  • a narrow-band band-pass filter (not shown) formed by a layered structure integrated into the fibre and formed by layers having different thickness and different refractive index so as to realize a phase-shifted Bragg grating .
  • the front end 12-a of the first collection fibre 12 may be provided with a non-shown high-pass optical filter formed by a layered structure integrated into the fibre and formed by layers having different thickness and different refractive index .
  • the high- pass optical filter is used to suppress Rayleigh scattering so that only the light at a greater wavelength, which has undergone Stokes scattering, is collected from the collection fibre 12 .
  • the end 8-a of the first emission fibre 8 may also be provided with a flat metalens-type structure (of known type and not further detailed) formed by nano structures configured to focus the ray emitted by the fibre 8.
  • metalens can advantageously replace optical lenses that are larger and bulkier .
  • Metalens structures with high numerical aperture can be used on the collection fibre 12 to increase collection efficiency .
  • the narrow-band band-pass filter and a focussing metalens structure can therefore coexist on the same emission fibre 8.
  • the high-pass filter and a high numerical aperture metalens structure can therefore coexist on the same collection fibre 12 .
  • the external tubular protection element 2 is inserted into a portion of human tissue until it reaches a position of interest to be subjected to analysis, e . g . a portion of liver 4
  • the optical signal generator 9 is activated (the solid-state laser is switched on) and thus the analysis of the signal received by means of the commercial Raman spectrometer 13 can start .
  • This spectrometer is controlled by a personal computer 21 which controls the entire system comprising the optoelectronic sensor realized according to the present invention, the laser source 9 and the Raman spectrometer 13.
  • the personal computer 21 installs signal processing software detected by the second optical collection fibre
  • the software 12 configured to compare the spectrum of the received signal with stored libraries containing spectra of known type .
  • the software also performs a qualitative and quantitative spectral analysis .
  • the functions performed by the processing software may be as follows : 1 . deletion of the background;
  • the classification operation may provide as output data the indication of different types of tissue cells such as normal cells and pathological cells .
  • the system enables in vivo Raman/Raman SERS analysis not otherwise possible, enabling real-time identification of the type of tissue cells to be analysed;
  • the handling system together with the lenses, allows the optical beam to be focused at different points with variable depth;
  • the system using different functionalised nanoparticles is versatile and can be specialised to identify a variety of tumour markers and thus identify various types of tumour pathologies for diagnostic and prognostic purposes;
  • the nanoparticles can be specific for different markers and a different reporter can be used as a code for each marker;
  • the number of fibres can be optimised in order to have the correct signal-to-noise ratio in reception .

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

Abstract

La présente invention concerne une sonde optoélectronique pour l'analyse de tissus situés à l'intérieur du corps humain, comprenant un élément de protection tubulaire externe flexible (2) configuré pour être inséré avec sa partie d'extrémité avant (3) dans un tissu (4) à soumettre à une analyse, un manchon interne (6) coulissant axialement à l'intérieur de l'élément tubulaire de protection (2) et pourvu d'une partie d'extrémité avant (6-a) qui est disponible entre une position de repos dans laquelle il est contenu dans l'élément tubulaire (2) et une position d'utilisation dans laquelle il fait saillie à partir de l'élément tubulaire (2). Le manchon interne comporte : un premier canal (7) logeant une première fibre optique (8) configurée pour fournir un signal d'excitation au tissu ; un deuxième canal (11) logeant une deuxième fibre optique (12) configurée pour recevoir un signal de réponse provenant du tissu ; un troisième canal (15) configuré pour alimenter un fluide contenant de préférence des nanoparticules au tissu (4) ; et un quatrième canal (17) logeant un élément expansible (17) configuré pour faire se projeter, lors de l'utilisation, à partir de l'extrémité (6-a) du manchon (6) lorsqu'il est agencé dans la position de repos pour se dilater et être agencé en contact avec les parois internes de l'élément de protection tubulaire externe (6) agissant comme un bouchon et séparant l'extrémité (6-a) du manchon (6) du tissu (4).
PCT/IT2022/000011 2022-02-24 2022-02-24 Sonde optoélectronique pour l'analyse de tissus situés a l'intérieur du corps humain WO2023161965A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/IT2022/000011 WO2023161965A1 (fr) 2022-02-24 2022-02-24 Sonde optoélectronique pour l'analyse de tissus situés a l'intérieur du corps humain

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IT2022/000011 WO2023161965A1 (fr) 2022-02-24 2022-02-24 Sonde optoélectronique pour l'analyse de tissus situés a l'intérieur du corps humain

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040073120A1 (en) * 2002-04-05 2004-04-15 Massachusetts Institute Of Technology Systems and methods for spectroscopy of biological tissue
US9086533B1 (en) * 2010-06-08 2015-07-21 Cirrex Systems, Llc Method and system for coupling light through challenging media
US20210068665A1 (en) * 2017-12-13 2021-03-11 President And Fellows Of Harvard College Endoscopic imaging using nanoscale metasurfaces

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040073120A1 (en) * 2002-04-05 2004-04-15 Massachusetts Institute Of Technology Systems and methods for spectroscopy of biological tissue
US9086533B1 (en) * 2010-06-08 2015-07-21 Cirrex Systems, Llc Method and system for coupling light through challenging media
US20210068665A1 (en) * 2017-12-13 2021-03-11 President And Fellows Of Harvard College Endoscopic imaging using nanoscale metasurfaces

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