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EP4482415A1 - Dispositif d'induction de perméabilité cellulaire dans une partie de tissu par optoporation - Google Patents

Dispositif d'induction de perméabilité cellulaire dans une partie de tissu par optoporation

Info

Publication number
EP4482415A1
EP4482415A1 EP22718812.5A EP22718812A EP4482415A1 EP 4482415 A1 EP4482415 A1 EP 4482415A1 EP 22718812 A EP22718812 A EP 22718812A EP 4482415 A1 EP4482415 A1 EP 4482415A1
Authority
EP
European Patent Office
Prior art keywords
tissue
laser beam
elongated body
opening
axis
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
EP22718812.5A
Other languages
German (de)
English (en)
Inventor
Carmen MIANO
Martina PROFETA
Donatella VECCHIONE
Andrea Cusano
Antonello Cutolo
Martino GIAQUINTO
Patrizio VAIANO
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Centro Regionale Information Communication Technology Scrl
Teoresi SpA
Original Assignee
Centro Regionale Information Communication Technology Scrl
Teoresi SpA
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 Centro Regionale Information Communication Technology Scrl, Teoresi SpA filed Critical Centro Regionale Information Communication Technology Scrl
Publication of EP4482415A1 publication Critical patent/EP4482415A1/fr
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B2017/00743—Type of operation; Specification of treatment sites
    • A61B2017/00747—Dermatology
    • A61B2017/00765—Decreasing the barrier function of skin tissue by radiated energy, e.g. using ultrasound, using laser for skin perforation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00053—Mechanical features of the instrument of device
    • A61B2018/0016—Energy applicators arranged in a two- or three dimensional array
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00452—Skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
    • A61B2018/2205—Characteristics of fibres
    • A61B2018/2211—Plurality of fibres
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
    • A61B2018/2255—Optical elements at the distal end of probe tips
    • A61B2018/2261—Optical elements at the distal end of probe tips with scattering, diffusion or dispersion of light

Definitions

  • the present invention relates to a device for inducing cell permeability in a portion of tissue by opto-poration .
  • Opto-poration involves the temporary and reversible permeabilisation of the lipid membranes of the cells by means of high intensity light (usually generated by laser) while leaving the other internal cell structures intact so as to preserve cell function and viability .
  • the main purpose of opto-poration is to facilitate the introduction of molecules into the cells, which is why it is used to assist the controlled local-regional or systemic release of drugs .
  • the mechanisms of permeabilisation of the cell membrane by laser are based on the absorption of electromagnetic energy by the cell membrane itself or by another absorbing agent placed close to it .
  • the absorption of electromagnetic energy can give rise to complex ef fects involving combinations of mechanical, thermal and chemical effects .
  • direct opto-poration occurs when the permeabilisation of the lipid membrane results from the direct interaction of a focal region of the laser with the membrane, which in this case constitutes the absorbing agent .
  • permeabilisation of the lipid membrane occurs as a result of absorption of the energy generated by the laser by an absorbing agent in contact with or near the cell (such as a particle or surface) , which generates secondary effects on the membrane .
  • patent US2013052725A1 describes a system for opto- poration comprising: a support for containing exogenous cells and molecules; an infrared (IR) light source that generates an IR optical beam and one or more focusing elements; an imaging device; a processor that generates a signal corresponding to a cell localization; and a light pattern shaper that is configured to temporally and spatially shape the optical beam on the cells for a period of time adapted to permeabilise the cell membrane .
  • IR infrared
  • Opto-poration of cells is achieved in known methods in a superficial manner by having the laser impinge on a tissue surface on which the cells are located, and for this reason deep tissue optoporation is not possible .
  • Aim of the present invention is to generate and use the phenomenon of the opto-poration in depth in a portion of tissue .
  • the foregoing aim is achieved by the present invention in that it relates to a device for inducing cell permeability in a portion of tissue by opto-poration of the type described in Claim 1 .
  • Figure 1 shows in side view a device for inducing cell permeability in a portion of tissue by opto-poration realized according to the present invention
  • Figure 2 shows a detail of the light deflection device 3 for opto-poration treatment of a portion of the human body shown in
  • Figure 3 shows an example of wavelengths that can be used with the device according to the present invention
  • Figure 4 shows a variant to the device shown in Figure 1;
  • Figure 5 shows a plurality of devices according to the present invention used in an arrayed electrode .
  • number 1 denotes a device for inducing cell permeability in a portion of tissue by opto-poration realized in accordance with the present invention .
  • the device 1 is needle-shaped and comprises an elongated body
  • the elongated body 2 is of tubular type and defines an internal cavity 4 coaxial to the axis H defined by a cylindrical wall 5 of the body 2; the internal cavity 4 communicates with the outside of the elongated body 2 through at least one opening 6 made at a second end of the elongated body 2.
  • two elongated openings 6 are provided along the axis H and arranged on opposite sides of the cylindrical wall 5. The opening 6 is then made on the cylindrical wall 5 and arranged at a predetermined distance from the tapered cutting end 3.
  • the opening 6 is approximately rectangular with the longer sides arranged parallel to the axis H . It is clear, however, that the opening 6 can have any shape and dimension and can be placed in any position along the body 2. The number of openings 6 is also variable
  • the opening 6 may be provided with a transparent closing and protective wall 6a, for example made of glass or polymer; examples of polymers that may be used are Poly (2-hydroxyethyl methacrylate) (pHEMA) , polymethyl methacrylate (PMMA) , siloxanes and hydrogel .
  • the closing and protective wall can also be made of poly (lactic-co-glycolic) acid
  • the elongated body 2 accommodates in the cavity 4 a waveguide 7 adapted to convey along the axis H a laser beam fed in input to the waveguide 7 and a deflection device 8 adapted to vary the direction of propagation of the laser beam so that the laser beam exits from the opening 6 propagating along a direction T transversal to the axis H so as to impinge, in use, the portion of tissue F arranged around the elongated body 2 .
  • the waveguide 7 is an optical fibre provided with a first end connected to a laser beam generating device 10 (of a known type shown schematically) and with a second end stably inserted into the elongated body 2 and producing precisely the waveguide 7.
  • a laser beam generating device 10 of a known type shown schematically
  • an optical fibre is a waveguide of dielectric material typically consisting of a cylindrical core surrounded by a cladding that has a different refractive index .
  • the optical fibre confines the electromagnetic energy in the form of light within the core and guides the light in a direction parallel to its axis .
  • the deflection device 8 is realized by dispersion materials or structures arranged or realized in the core or in the cladding of the fibre to achieve the diffusion of light from the core to the cladding and therefore along the transverse direction T through the opening 6.
  • optical fibre known by the trade name FibranceTM of the manufacturer Corning can be used, which can emit light laterally on sections with length nominally ranging from 0. 5 cm to 10 metres, over a wide wavelength range .
  • the optical fibre 7 is characterised by an extremely reduced diameter, typically a few hundred pm .
  • the device 1 or a plurality of devices 1 are inserted into a portion of tissue to be treated so that the end portions 3 are inserted into that portion of tissue. This operation can be carried out under local anaesthesia .
  • each device 1 directs the laser beam transversely to the axis H and hits the cells present in the tissue portion .
  • the laser beam generating device produces a laser beam with a wavelength ranging between 500 and ⁇ 1500nm, i . e . in the region ranging from orange in the visible spectrum to near infrared (NIR) .
  • the power can be supplied both in continuous mode and in pulsed mode with pulse duration that can be pushed up to the second femur [see for example : Tuchin, V. V. (2003) . Light-tissue interactions . Biomedical Photonics Handbook, 3-1. ] .
  • the preferable exploitation regime is the one in which only
  • the tissue portion must be provided with power densities that can vary from a minimum of the order of
  • Power density, exposure time and pulse duration will be appropriately dimensioned in order to achieve a given temperature in a precise region of the tissue, also taking into account the actual arrangement of the device 1. Power densities higher than
  • MW/cm s may give rise to other non-reversible effects such as photoablation and photo-disgregation .
  • the device 1 could comprise several optical fibres (for example, two optical fibres 7a and 7b as shown in Figure 4) housed in the cavity 4 (or in respective parallel cavities 4a, 4b) and each provided with a respective side-emitting deflection device 8 adapted to vary the direction of propagation of the laser beam so that the laser beam exits from a respective opening 6a, 6b made in the cylindrical wall propagating along a direction T transversal to the axis H so that laser beams are produced which impinge on different portions of tissue .
  • Such optical fibres 7a, 7b are connected with respective outputs of laser beam generating device 10a of a laser treatment apparatus configured to provide the optical fibres 7a and
  • the operating regime in terms of pulse duration and exposure time, may be different for each of the fibres 7a, 7b used.
  • the elongated body 2 could be provided with a capillary hole
  • the transparent closing and protective wall 6a could be made of a material adapted to transmit light and at the same time releasing a drug by using hydrogel .
  • the final device could consist of a number of needles greater than one; in this case, an arrayed electrode is made comprising a support structure 11 that keeps each device 1 in a stable position with respect to the other devices 1 while also maintaining the parallelism between the axes H .
  • the number and the spatial arrangement of the devices 1 depend on the extension of the region to be treated and the type of tissue .

Landscapes

  • Health & Medical Sciences (AREA)
  • Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Electromagnetism (AREA)
  • Optics & Photonics (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Otolaryngology (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Radiation-Therapy Devices (AREA)

Abstract

Dispositif d'induction de perméabilité cellulaire dans une partie de tissu par optoporation comprenant un corps allongé (2) le long d'un axe H pourvu d'une première extrémité de coupe conique (3) formée pour percer la peau et/ou le tissu sous-jacent et être insérée dans une partie (F) de tissu ; le corps allongé (2) est du type tubulaire et définit une cavité interne (4) définie par une paroi latérale (5) et est pourvu d'au moins une ouverture (6) réalisée sur la paroi latérale (5) et agencée à une distance prédéterminée de l'extrémité de coupe conique (3). Le corps allongé loge dans la cavité (4) un guide d'ondes (7) configuré pour transporter un faisceau laser alimenté en entrée dans le guide d'ondes et un dispositif de déviation d'émission latérale (8) conçu pour faire varier la direction de propagation du faisceau laser de telle sorte que le faisceau laser sort de l'ouverture (6) en se propageant transversalement à l'axe (H) de façon à frapper la partie de tissu (F) agencée autour du corps allongé (2).
EP22718812.5A 2022-02-24 2022-02-24 Dispositif d'induction de perméabilité cellulaire dans une partie de tissu par optoporation Pending EP4482415A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IT2022/000012 WO2023161966A1 (fr) 2022-02-24 2022-02-24 Dispositif d'induction de perméabilité cellulaire dans une partie de tissu par optoporation

Publications (1)

Publication Number Publication Date
EP4482415A1 true EP4482415A1 (fr) 2025-01-01

Family

ID=81386523

Family Applications (1)

Application Number Title Priority Date Filing Date
EP22718812.5A Pending EP4482415A1 (fr) 2022-02-24 2022-02-24 Dispositif d'induction de perméabilité cellulaire dans une partie de tissu par optoporation

Country Status (2)

Country Link
EP (1) EP4482415A1 (fr)
WO (1) WO2023161966A1 (fr)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2184021A (en) * 1985-12-13 1987-06-17 Micra Ltd Laser treatment apparatus for port wine stains
CA2276312C (fr) * 1996-12-31 2012-11-27 Jonathan A. Eppstein Formation de micropores sur un tissu pour l'administration d'agents bioactifs
US20050095578A1 (en) * 2003-10-31 2005-05-05 Koller Manfred R. Method and apparatus for cell permeabilization
US20130052725A1 (en) * 2011-08-30 2013-02-28 General Electric Company System for optical based delivery of exogenous molecules to cells
US20170319715A1 (en) * 2016-02-08 2017-11-09 Circuit Therapeutics, Inc. System and method to modulate pain and itch through cutaneous transfer of genetic information

Also Published As

Publication number Publication date
WO2023161966A1 (fr) 2023-08-31

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