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WO2025125853A1 - Électroporation/électrochimiothérapie de régions internes faiblement infectées - Google Patents

Électroporation/électrochimiothérapie de régions internes faiblement infectées Download PDF

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Publication number
WO2025125853A1
WO2025125853A1 PCT/IB2023/062473 IB2023062473W WO2025125853A1 WO 2025125853 A1 WO2025125853 A1 WO 2025125853A1 IB 2023062473 W IB2023062473 W IB 2023062473W WO 2025125853 A1 WO2025125853 A1 WO 2025125853A1
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WO
WIPO (PCT)
Prior art keywords
electrodes
exemplary
support tube
exemplary embodiment
electrical
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
PCT/IB2023/062473
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English (en)
Inventor
Mohammad ABDOLAHAD
Mohammad Ali Khayamian
Hamed Abadijoo
Farshid ROSTAMI POURIA
Majid HASANLOO
Navid MANOOCHEHRI
Hossein Simaee
Seyed Mojtaba Yazdanparast
Alvand NASERGHANDI
Kosar NAMAKIN
Seyed Rouhollah MIRI
Habibollah MAHMOODZADEH
Sepideh MANSOURI
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Individual
Original Assignee
Individual
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Priority to PCT/IB2023/062473 priority Critical patent/WO2025125853A1/fr
Publication of WO2025125853A1 publication Critical patent/WO2025125853A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/327—Applying electric currents by contact electrodes alternating or intermittent currents for enhancing the absorption properties of tissue, e.g. by electroporation
    • 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
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00613—Irreversible electroporation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36002—Cancer treatment, e.g. tumour

Definitions

  • the present disclosure generally relates to methods and apparatus for target cells’ ablation and/or delivery of therapeutic agents into a target cell via an electroporation process, and particularly, to an electroporation probe with a structure and an arrangement of electrodes appropriate for applying electroporation to target cells located in sensitive internal regions and/or internal areas of a patient’s body which are difficult to access.
  • Radiofrequency (RF) methods are examples of heating methods in which high frequency electromagnetic waves are used.
  • RF Radiofrequency
  • Each of these methods has prominent features and on the other hand has certain disadvantages, for example, heating-based methods cannot be used near main vessels due to a destruction of intercellular matrix.
  • chemotherapy-based methods also cause problems for a patient.
  • One of the biggest and most common problems in cancer chemotherapy is side effects of drugs on healthy tissues and creation of physiological problems in vital organs of body. Many cancer deaths are due to side effects of chemotherapy drugs on vital organs of body.
  • Today, one of the most important areas of research in cancer treatment is construction of targeted drug delivery systems to tumor areas that cause minimal damage to healthy body tissues.
  • One of the minimally invasive newly proposed methods is treatment of cancer based on electroporation.
  • holes are created on cancer cells by applying high voltage electrical pulses, which cause permeability of cancer cells.
  • Holes created by electroporation may have different lifetimes based on their size, and larger holes may last longer. Pore lifetime spans from milliseconds to hours. Holes with long life-times (more than a few hours) may disrupt the tissue homeostasis and result cell death.
  • the holes created on cells can be reversible, and as a result, the hole closes after the end of electrical pulse application, and finally, cells will survive.
  • This method is used to deliver more chemotherapy drugs to tumor cells named as electrochemotherapy (ECT) since considerable enhances the efficiency of local chemotherapy.
  • ECT electrochemotherapy
  • IRE irreversible electroporation
  • ECT tumor cells
  • IRE irreversible electroporation
  • treatment can be done in form of ECT or IRE.
  • high voltage electrical pulses are applied to target cancer cells or cancerous tissue in a short period of time, which leads to a disruption of ionic potential balance of cell membrane; thereby, resulting in generating holes on cells and increasing permeability of cells.
  • Needle-based electrodes are mostly used for electroporation treatments, and many improvements and efforts have been made to fabricate and utilize electroporation devices having needle electrodes.
  • A. Westersten et al. disclosed in a US patent application numbered as US 2006/0264807 Al a modular electrode system including a non-symmetrically arranged plurality of needle electrodes, in which a constant-current electrical pulse is applied to the plurality of needle electrodes.
  • the modular electrode system may facilitate delivery of electrical energy to tissues in a manner that assures that the energy dose delivered lies consistently between an upper limit a lower limit; thereby, providing increased electroporation efficiencies.
  • conventional electrodes that are mostly utilized in electrochemotherapy have many drawbacks and design weaknesses.
  • conventional needle electrodes cannot be used in sensitive tissues, such as vessels, nerves, intestines, etc. due to bleeding in tissues and/or perforation of vital organs.
  • plate electrodes are not effective in applying electrochemotherapy stimulation due to a lack of a proper interaction surface between tissue and electrode.
  • a physician is dealing with spaces where it is not possible to apply electrochemotherapy stimulation due to a lack of a proper access.
  • Electroporation devices having less-invasive, and preferably, non-invasive electrodes.
  • a device with electrodes to apply electroporation to cells, which have a structure that minimizes a possibility of damage and bleeding to sensitive tissues (including vascular tissues, nervous tissues, etc.).
  • sensitive tissues including vascular tissues, nervous tissues, etc.
  • electrodes that allow access to areas that cannot be reached with conventional electrodes.
  • electroporation devices having electrodes with an arrangement, size, number, and shape designed and configured to transfer an electric field that can cover wide areas having specific shapes in a living body.
  • the present disclosure is directed to a tubular probe for non- invasive electrically stimulation of a plurality of target cells in an internal target region of a living body.
  • the tubular probe may include a support tube including a distal end and a proximal end, a first set of electrodes including a plurality of circumferential rings positioned around the support tube in an axially spaced apart relation from each other along the support tube, a head part attached to the distal end of the support tube including a second set of electrodes, and a plurality of electrical connectors utilized for connecting the first set of electrodes and the second set of electrodes to an electrical stimulator device.
  • the distal end of the support tube may be inserted into the internal target region via guiding the proximal end of the support tube.
  • the first set of electrodes may be put in contact with the internal target region.
  • the head part may include an electrode substrate engaged to the distal end of the support tube.
  • the head part may include at least two apertures.
  • the second set of electrodes may include at least two U-shaped wires separately protruded out from the at least two apertures.
  • the second set of electrodes may be put in contact with the internal target region.
  • the support tube may include a plurality of openings thereon.
  • the plurality of electrical connectors may pass through the support tube.
  • the plurality of electrical connectors may include a first set of electrical connectors and a second set of electrical connectors.
  • the first set of electrical connectors may be utilized for connecting the first set of electrodes to the electrical stimulator device and the second set of electrical connectors may be utilized for connecting the second set of electrodes to the electrical stimulator device.
  • each electrical connector of the plurality of electrical connectors may include an electrically conductive line with a distal end and a proximal end.
  • the proximal end of each electrical connector of the plurality of electrical connectors may be in connection with, or capable of connection with, the electrical stimulator device.
  • each electrical connector of the first set of electrical connectors may be passed through an opening of the plurality of openings and attached to a circumferential ring of the plurality of circumferential rings.
  • the distal end of each electrical connector of the first set of electrical connectors may fasten the respective circumferential ring around the support tube.
  • the distal end of each electrical connector of the second set of electrical connectors may be attached to a U-shaped wire of the at least two U-shaped wires.
  • the support tube may include an elongated tube made of a biocompatible flexible material.
  • the support tube may include a biocompatible polymeric tube.
  • the support tube may include a tube with a diameter in a range of 0.5 cm to 3 cm.
  • each opening of the plurality of openings may include a hole on the support tube with a diameter in a range of 0. 1 cm to 0.5 cm.
  • each two adjacent openings may be arranged within a distance in a range of 0.5 cm to 1.5 cm from each other.
  • each electrode of the first set of electrodes may include an electrically conductive biocompatible ring with an internal diameter in a range of 0.5 cm to 3 cm and an external diameter in a range of 0.7 cm to 3.5 cm.
  • each U-shaped wire of the at least two U-shaped wires may include a biocompatible electrically conductive wire with a diameter in a range of about 0.5 mm to about 3 mm.
  • the at least two U-shaped wires may be arranged in parallel to each other with a distance in a range of 0.5 cm to 1.5 cm between each two adjacent U-shaped wires of the at least two U-shaped wires.
  • the present disclosure is directed to a system for in-vivo electroporation of a plurality of target cells in an internal target region of a living body.
  • the system may include a tubular probe, an electrical pulse generator electrically connected to the tubular probe, and a processing unit electrically connected to the electrical pulse generator.
  • the tubular probe may be utilized to transfer a pulsed electric field to the plurality of target cells.
  • the tubular probe may include a support tube including a distal end and a proximal end, a first set of electrodes including a plurality of circumferential rings positioned around the support tube in an axially spaced apart relation from each other along the support tube, a head part attached to the distal end of the support tube including a second set of electrodes, and a plurality of electrical connectors utilized for connecting the first set of electrodes and the second set of electrodes to the electrical pulse generator.
  • the distal end of the support tube may be inserted into the internal target region via guiding the proximal end of the support tube.
  • the first set of electrodes may be put in contact with the internal target region.
  • the head part may include an electrode substrate engaged to the distal end of the support tube.
  • the head part may include at least two apertures.
  • the second set of electrodes may include at least two U-shaped wires separately protruded out from the at least two apertures.
  • the second set of electrodes may be put in contact with the internal target region.
  • each electrical connector of the plurality of electrical connectors may be in connection with, or capable of connection with, the electrical pulse generator.
  • the distal end of each electrical connector of the first set of electrical connectors may be passed through an opening of the plurality of openings and attached to a circumferential ring of the plurality of circumferential rings.
  • the distal end of each electrical connector of the first set of electrical connectors may fasten the respective circumferential ring around the support tube.
  • the distal end of each electrical connector of the second set of electrical connectors may be attached to a U-shaped wire of the at least two U-shaped wires.
  • the electrical pulse generator may be utilized to apply a pulsed electric field between at least two electrodes of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof.
  • each proximal end of each electrically conductive line of the at least two electrodes may be connected to a different pole of two poles of the electrical pulse generator.
  • the processing unit may include a memory having processor-readable instructions stored therein and a processor.
  • the processor may access the memory and execute the processor-readable instructions.
  • the processor may be utilized to perform a method when the processor-readable instructions are executed by the processor.
  • the method may include inducing electroporation to the plurality of target cells by generating the pulsed electric field between the at least two electrodes of at least two electrodes of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof inside the internal target region via applying at least one sequence of electric voltage pulses between the at least two electrodes utilizing the electrical pulse generator.
  • applying the at least one sequence of electric voltage pulses between the at least two electrodes may include applying at least one sequence of eight square-wave electric voltage pulses with a magnitude in a range of 500 V/cm to 1500 V/cm and a duration of 100 ps between the at least two electrodes.
  • the method may further include generating the pulsed electric field between every two electrodes of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof by periodically changing a connection of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof to the two poles of the electrical pulse generator.
  • periodically changing the connection of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof to the two poles of the electrical pulse generator may include periodically substituting connection of at least one electrode of the at least two electrodes by a different electrode of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof.
  • substituting connection of the at least one electrode of the at least two electrodes by the different electrode of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof may include electrically disconnecting the at least one electrode of the at least two electrodes from a first pole of the electrical pulse generator and electrically connecting the different electrode of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof to the first pole of the electrical pulse generator.
  • periodically changing the connection of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof to the two poles of the electrical pulse generator may include stepwise changing the connection of at least one of the first set of electrodes, the second set of electrodes, and combinations thereof to the two poles of the electrical pulse generator during a plurality of time steps.
  • each time step of the plurality of time steps may include a time interval between 0.5 second and 5 seconds.
  • the support tube may include an elongated tube made of a biocompatible flexible material.
  • the support tube may include a biocompatible polymeric tube.
  • the support tube may include a tube with a diameter in a range of 0.5 cm to 3 cm.
  • each opening of the plurality of openings may include a hole on the support tube with a diameter in a range of 0. 1 cm to 0.5 cm.
  • each two adjacent openings may be arranged within a distance in a range of 0.5 cm to 1.5 cm from each other.
  • each electrode of the first set of electrodes may include an electrically conductive biocompatible ring with an internal diameter in a range of 0.5 cm to 3 cm and an external diameter in a range of 0.7 cm to 3.5 cm.
  • each U-shaped wire of the at least two U-shaped wires may include a biocompatible electrically conductive wire with a diameter in a range of about 0.5 mm to about 3 mm.
  • the at least two U-shaped wires may be arranged in parallel to each other with a distance in a range of 0.5 cm to 1.5 cm between each two adjacent U-shaped wires of the at least two U-shaped wires.
  • FIG. 1A schematically shows an exemplary tubular probe, consistent with one or more exemplary embodiments of the present disclosure.
  • FIG. IB shows a first exploded view of an exemplary tubular probe, consistent with one or more exemplary embodiments of the present disclosure.
  • FIG. 1C shows a second exploded view of an exemplary tubular probe, consistent with one or more exemplary embodiments of the present disclosure.
  • FIG. ID shows a top view of an exemplary tubular probe, consistent with one or more exemplary embodiments of the present disclosure.
  • FIG. IE shows an exemplary system for electrical stimulation of an exemplary target region in a living body using an exemplary tubular probe, consistent with one or more exemplary embodiments of the present disclosure.
  • FIG. 2 shows an exemplary method for electroporation of an exemplary plurality of target cells, consistent with one or more exemplary embodiments of the present disclosure.
  • FIG. 3 shows an example computer system in which an embodiment of the present disclosure, or portions thereof, may be implemented as computer-readable code, consistent with one or more exemplary embodiments of the present disclosure.
  • methods, systems, and devices are disclosed for an electrical treatment (e.g., electroporation) of target cells, particularly cells of a patient's tissues.
  • methods and devices may be utilized for target cells’ ablation (e.g., tumor cells destruction) and/or delivery of a substance (e.g., a drug, a diagnostic agent, atherapeutic agent, etc.) to exemplary target cells.
  • a substance e.g., a drug, a diagnostic agent, atherapeutic agent, etc.
  • an exemplary device e.g., a probe
  • target cell’s electroporation having two or more electrodes designed based on a location, extent, and accessibility of target cells and specific properties of exemplary target cells.
  • an exemplary device and electrodes thereof may be designed based on shape, location, and extent of a target area containing exemplary target cells and surrounding areas to be electrically stimulated/treated.
  • electrodes of an exemplary device may be non-invasive electrodes while needle electrodes of conventional electroporation devices may be invasive and unsuitable for all parts of a patient’s body.
  • an exemplary probe may be utilized for electrical stimulation of a plurality of target cells located in an internal part of a living body.
  • an exemplary probe may be utilized for electrical stimulation of a plurality of target cells located in at least one of a tubular area, a cavity-shaped area, or an area with a tubular access path there into.
  • an exemplary probe may have a tubular shape adapted to be properly used in tubular and cavity-shaped areas.
  • an exemplary probe may include a support tube with two sets of electrodes mounted thereon.
  • an exemplary probe may include a first set of electrodes including a plurality of circumferential electrically conductive rings mounted around an outer surface of an exemplary support tube.
  • an exemplary probe may further include a second set of electrodes including flat electrically conductive wire blades mounted on a front surface of an exemplary probe.
  • a number, size, distance between adjacent electrodes, and other design parameters of each of an exemplary first set of electrodes and an exemplary second set of electrodes may be selected based on a target region containing an exemplary plurality of target cells to be treated.
  • an exemplary probe may be utilized for a non-invasive electrical treatment of a plurality of target cells, which may be located at a hard-to-access location in a living body of a human or an animal.
  • an exemplary probe may be utilized for non-invasive electrical treatment of an exemplary plurality of target cells located at areas of an exemplary living body where there is only a tubular access to exemplary areas.
  • an exemplary probe may be utilized for a non- invasive electrical treatment of a plurality of target cells located at a location of at least one of at least one of rectum, vagina, colon, esophagus, tracheal, artery, vein, intestine, stomach, bladder, anus entrance, a narrow space inside at least one of digestive, respiratory, urogenital organs, or vessels, and combinations thereof.
  • tubular shape and arrangement of an exemplary first set of electrodes and an exemplary second set of electrodes of an exemplary probe may provide generating an electric field all over an exemplary target region; thereby, resulting in a highly effective electrical stimulation of an exemplary target region.
  • an exemplary probe may be utilized for at least one of electrically stimulating of an exemplary plurality of target cells, electroporating an exemplary plurality of target cells, generating an electric field among an exemplary plurality of target cells, electrochemotherapy (ECT) of an exemplary plurality of target cells, electrically ablation of an exemplary plurality of target cells, and combinations thereof.
  • an exemplary probe may be utilized for at least one of electrically stimulating of an exemplary plurality of target cells in an area of an exemplary living body, where inserting a needle electrode there into may not be allowed or inserting a needle there may be harmful.
  • target cells may refer to cells of a part of a living body to be treated by an electrical stimulation (e.g., electroporation); allowing for treatment of exemplary cells including ablating exemplary cells and/or delivery of specific substances (e.g., a drug, a diagnostic agent, a therapeutic agent, etc.) to exemplary cells.
  • an electrical stimulation e.g., electroporation
  • specific substances e.g., a drug, a diagnostic agent, a therapeutic agent, etc.
  • FIG. 1A schematically shows a tubular probe 100, consistent with one or more exemplary embodiments of the present disclosure.
  • tubular probe 100 may include a support tube 102, a first set of electrodes 104 positioned around support tube 102, a head part 106 attached to a distal end 102a of support tube 102.
  • head part 106 may include a second set of electrodes 108.
  • tubular probe 100 may be utilized to be inserted into a living body.
  • tubular probe 100 may be utilized to be inserted into a target region of an exemplary living body.
  • an exemplary target region may include a plurality of target cells to be treated using tubular probe 100.
  • an exemplary target region may include an internal target region inside an exemplary living body.
  • tubular probe 100 may be utilized to be inserted into an exemplary target region in the vicinity of a plurality of target cells of an exemplary target region.
  • an exemplary plurality of target cells may include a plurality of cancer cells.
  • an exemplary plurality of target cells may include at least one of a plurality of cancer cells of a tumor mass, a plurality of remained cancer cells of a resected tumor, a plurality of cancer cells spread throughout an exemplary target region, and combinations thereof.
  • an exemplary plurality of target cells may be ablated or destructed using tubular probe 100 through an electrical stimulation treatment.
  • tubular probe 100 may be utilized to transfer an electrical signal to an exemplary plurality of target cells to be treated by an exemplary electrical stimulation.
  • tubular probe 100 may be utilized to transfer a pulsed electrical signal to an exemplary plurality of target cells to be treated by an electroporation mechanism.
  • distal end 102a of support tube 102 may be entered into an exemplary target region, and a location and movement of support tube 102 inside an exemplary target region may be adjusted by guiding a proximal end 102b of support tube 102; allowing for putting first set of electrodes 104 and/or second set of electrodes 108 in contact or in the vicinity of an exemplary plurality of target cells.
  • an electric field may be generated among first set of electrodes 104 and/or second set of electrodes 108 in the vicinity of an exemplary plurality of target cells by applying an exemplary electrical signal between two or more electrodes of each of first set of electrodes 104 and/or second set of electrodes 108.
  • an exemplary electric field may be generated using an electrical stimulator device (e.g., an electrical pulse generator) electrically connected/coupled to exemplary two or more electrodes first set of electrodes 104 and second set of electrodes 108.
  • support tube 102 may include an elongated tube made of a biocompatible flexible material.
  • support tube 102 may include distal end 102a and proximal end 102b.
  • support tube 102 may include a biocompatible polymeric tube.
  • support tube 102 may include a tube made of at least one of silicone rubber, polyethylene terephthalate (PET), polydimrthylsiloxane (PDMS), and combinations thereof.
  • support tube 102 may include a tube with a diameter 112 in a range of about 0.5 cm to about 3 cm.
  • first set of electrodes 104 may include a plurality of circumferential rings mounted on support tube 102 surrounding support tube 102.
  • each electrode 104a of first set of electrodes 104 may include a ring attached to support tube 102.
  • first set of electrodes 104 may be arranged separately circumferentially around support tube 102 along a longitudinal axis 110 of support tube 102.
  • first set of electrodes 104 may be positioned around support tube 102 in an axially spaced apart relation from each other along longitudinal axis 110 of support tube 102.
  • each electrode 104a may include an electrically conductive biocompatible ring.
  • each electrode 104a may include a ring made of stainless steel.
  • each electrode 104a may include a ring made of stainless steel 304 or stainless steel 316.
  • each electrode 104a may have an internal diameter 114 in a range of about 0.5 cm to about 3 cm and an external diameter 116 in a range of about 0.7 cm to about 3.5 cm.
  • each electrode 104a may have internal diameter 114 equal to diameter 112 of support tube 102 and external diameter 116 of about 0.5 cm more than internal diameter 114.
  • support tube 102 may include a silicone rubber tube with diameter 112 of about 2 cm and each electrode 104a may include a stainless steel ring with internal diameter 114 of about 2 cm and external diameter 116 of about 2.5 cm mounted around support tube 102.
  • each two adjacent electrodes 104b and 104c may be arranged at a distance 118 in a range of about 0.5 cm to about 1.5 cm from each other.
  • exemplary distance 118 between exemplary two adjacent electrodes 104b and 104c may be different or equal to a distance 117 between another exemplary two adjacent electrodes 104c and 104d.
  • FIGs. IB and 1C show two exploded views of tubular probe 100, consistent with one or more exemplary embodiments of the present disclosure.
  • FIG. ID shows a top view of tubular probe 100, consistent with one or more exemplary embodiments of the present disclosure.
  • head part 106 may be attached to distal end 102a of support tube 102.
  • head part 106 may include an electrode substrate 107 engaged to distal end 102a of support tube 102 and second set of electrodes 108 mounted on electrode substrate 107.
  • second set of electrodes 108 may include two or more electrodes.
  • second set of electrodes 108 may include two or more U-shaped wires, for example, U-shaped wires 108a and 108b.
  • exemplary U-shaped wire 108a may include a flat base 109a with two parallel lateral edges 109b and 109c extending upwards from flat base 109a.
  • each U- shaped wire 108a may include a biocompatible electrically conductive wire with a diameter in a range of about 0.5 mm to about 3 mm.
  • U-shaped wire 108a may be made of steel.
  • U-shaped wire 108a may be made of medical grade stainless steel.
  • electrode substrate 107 may include atop part 107a and a bottom part 107b engaged to distal end 102a of support tube 102.
  • top part 107a may include at least two apertures 124a and 124b for mounting U- shaped wires 108a and 108b on electrode substrate 107.
  • U- shaped wires 108a and 108b may be protruded out from corresponding apertures 124a and 124b.
  • a first lateral edge 109b may pass through a first aperture 124a and a second lateral edge 109c may pass through a second aperture 124b.
  • a length in a range of about 0.1 mm to about 0.5 mm of each lateral edge 109b and 109c may be protruded out from top part 107a of electrode substrate 107.
  • flat base 109a of U-shaped wire 108a may have a length 126 in a range of about 0.5 cm to about 1.5 cm.
  • second set of electrodes 108 may be arranged parallel to each other.
  • each two adjacent U-shaped wires 108a and 108b of second set of electrodes 108 may be in parallel relation to each other with a distance 128 in a range of about 0.5 cm to about 1 .5 cm from each other.
  • first set of electrodes 104 may allow for generating an exemplary electric field inside an exemplary living body within a space all around tubular probe 100.
  • second set of electrodes 108 may allow for generating an exemplary electric field inside an exemplary living body in front of tubular probe 100.
  • an exemplary arrangement of first set of electrodes 104 in addition to second set of electrodes 108 may provide covering an exemplary generated electric field within all spaces around tubular probe 100; allowing to ensure all exemplary target cells may be electrically stimulated by adjusting a location of tubular probe 100 inside an exemplary living body during just one insertion of tubular probe 100 into an exemplary living body.
  • such arrangement of first set of electrodes 104 and second set of electrodes 108 may allow for generating an exemplary electric field non-invasively and exactly at an exemplary target region not stimulating cells of nearby tissues other than an exemplary plurality of target cells.
  • tubular probe 100 may further include a plurality of electrical connectors 120.
  • each electrical connector of plurality of electrical connectors 120 may include an electrically conductive line.
  • each electrical connector of plurality of electrical connectors 120 may include an electrically conductive wire.
  • each electrical connector of plurality of electrical connectors 120 may connect an electrode of first set of electrodes 104 or second set of electrodes 108 to an exemplary electrical stimulator device.
  • plurality of electrical connectors 120 may include a first set of electrical connectors 120a-120f and a second set of electrical connectors 120g and 120h.
  • a number of plurality of electrical connectors 120 may be equal to number of electrodes of first set of electrodes 104 in addition to second set of electrodes 108 and not limited to an exemplary number of electrical connectors 120 shown in FIG. IB.
  • plurality of electrical connectors 120 may pass through support tube 102.
  • each electrical connector 120a of first set of electrical connectors 120a-120f may have a distal end 121 attached to a corresponding electrode 104a of first set of electrodes 104.
  • each electrical connector 120g of second set of electrical connectors 120g and 120h may have a distal end 123 attached to a corresponding electrode 108a of second set of electrodes 108.
  • an exemplary electrode 108a may be attached to distal end 123 using at least one of soldering, welding, an irreversible connection, an electrically conductive paste, and combinations thereof.
  • support tube 102 may include a plurality of openings 122 thereon.
  • plurality of openings 122 may be used to fasten first set of electrodes 104 around support tube 102.
  • first set of electrical connectors 120a-120f may be used to fasten each electrode 104a of first set of electrodes 104 at a location of a corresponding opening 122a of plurality of openings 122.
  • each opening 122a of plurality of openings 122 may include a hole on support tube 102 with a diameter in a range of about 0. 1 cm to about 0.5 cm.
  • each two adjacent openings 122a and 122b of plurality of openings 122 may be arranged within a distance 125 in a range of about 0.5 cm to about 1.5 cm from each other.
  • distance 125 between two exemplary adjacent openings 122a and 122b of plurality of openings 122 may be different or equal to a distance 127 between two exemplary adjacent openings 122c and 122d of plurality of openings 122.
  • each electrical connector 120a of first set of electrical connectors 120a-120f may be passed through each opening 122a of plurality of openings 122, and distal end 121 of electrical connector 120a may be attached to electrode 104a of first set of electrodes 104.
  • an exemplary attachment between distal end 121 and electrode 104a may result in fixing and fastening electrode 104a around support tube 102.
  • an exemplary electrode 104a may be attached to distal end 121 using at least one of soldering, welding, an irreversible connection, an electrically paste, and combinations thereof.
  • tubular probe 100 may be utilized for an electrical treatment of an exemplary plurality of target cells located in an exemplary target region of an exemplary living body (i.e., a human, or an animal).
  • tubular probe 100 may be utilized for generating an electric field between at least two electrodes of first set of electrodes 104 and/or at least two electrodes of second set of electrodes 108 inside an exemplary target region; allowing for electrically stimulation of an exemplary plurality of target cells.
  • tubular probe 100 may be utilized for an exemplary electrical treatment of an exemplary plurality of target cells in an exemplary target region, where an invasive insertion of a needle-like electrode may not be allowed due to a sensitiveness of an exemplary target region. Furthermore, tubular probe 100 may be utilized for an exemplary electrical treatment of an exemplary plurality of target cells in an exemplary target region, where an access there into is limited and an exemplary target region may be accessible only by a flexible tubular structure of tubular probe 101.
  • an exemplary target region may include at least one of rectum, vagina, colon, esophagus, tracheal, artery, vein, intestine, stomach, bladder, anus entrance, a narrow space inside at least one of digestive, respiratory, urogenital organs, or vessels, and combinations thereof.
  • an exemplary electrical treatment of an exemplary plurality of target cells may include in-vivo electroporation of an exemplary plurality of target cells.
  • first set of electrodes 104 and/or second set of electrodes 108 may be utilized for transferring a pulsed electric field from an exemplary electrical pulse generator to an exemplary plurality of target cells while tubular probe 100 is put in contact with an exemplary target region.
  • tubular probe 100 may be put in contact with an exemplary target region via insertion of tubular probe 100 into an exemplary living body in the vicinity of an exemplary target region.
  • a portion of tubular probe 100 including first set of electrodes 104 and/or second set of electrodes 108 may be inserted into an exemplary target region.
  • an electric potential may be applied between at least two electrodes of first set of electrodes 104 and/or second set of electrodes 108 so that an exemplary electric field may be generated in an area including an exemplary plurality of target cells.
  • a pulsed electric field may be applied between at least two electrodes of first set of electrodes 104 and/or second set of electrodes 108, and an exemplary pulsed electric field may be generated inside an exemplary target region including an exemplary plurality of target cells.
  • an exemplary plurality of target cells of at least one of an exemplary tissue, an exemplary organ, or an exemplary portion thereof may be affected by an exemplary electric field applied between at least two electrodes of first set of electrodes 104 and/or second set of electrodes 108.
  • an exemplary plurality of target cells may be electroporated due to an exemplary pulsed electric field applied between at least two electrodes of first set of electrodes 104 and/or second set of electrodes 108.
  • an exemplary stimulated plurality of target cells may be ablated or destructed.
  • tubular probe 100 may be utilized for applying a therapeutic method via electrical stimulation (e.g., electroporation) of an exemplary plurality of target cells of an exemplary living body, for example, tumor cells of a cancer patient.
  • an exemplary target region may be swept and scanned by moving tubular probe 100 throughout an exemplary target region and applying an exemplary electric field; thereby, resulting in electrically stimulating (e.g., electroporating) of all exemplary plurality of target cells.
  • tubular probe 100 may be moved throughout an exemplary target region by moving proximal end 102b of support tube 102 of tubular probe 100.
  • FIG. IE shows a system 130 for electrical stimulation of an exemplary target region in a living body using tubular probe 100, consistent with one or more exemplary embodiments of the present disclosure.
  • system 130 may include tubular probe 100, an electrical stimulator device 132, and a processing unit 134.
  • electrical stimulator device 132 may include a power supply or an electrical voltage generator.
  • electrical stimulator device 132 may include an electrical pulse generator.
  • electrical stimulator device 132 may include an electroporation pulse generator.
  • tubular probe 100 may be electrically connected to electrical stimulator device 132 via plurality of electrical connectors 120.
  • two or more electrodes of first set of electrodes 104 and/or second set of electrodes 108 of tubular probe 100 may be electrically connected to electrical stimulator device 132 via two or more respective electrical connectors of plurality of electrical connectors 120.
  • At least one electrical connector 120a of plurality of electrical connectors 120 attached to a corresponding electrode 104a may have a proximal end 131 connected to a first pole 132a of electrical stimulator device 132, and at least another electrical connector 120b of plurality of electrical connectors 120 attached to a corresponding electrode 104b may have a proximal end 133 connected to a second pole 132b of electrical stimulator device 132.
  • electrical stimulator device 132 may be utilized to apply an electrical signal between one or more pairs of first set of electrodes 104 and/or second set of electrodes 108 while first set of electrodes 104 and/or second set of electrodes 108 being put in contact with an exemplary target region in an exemplary living body including an exemplary plurality of target cells; therefore, an electric field within an exemplary target region may be generated and an exemplary plurality of target cells may be electrically stimulated.
  • electrical stimulator device 132 may be utilized to apply an exemplary electrical signal between electrode 104a and electrode 104b; thereby, resulting in generating an electric field in an area of an exemplary target region between and around two electrodes 104a and 104b.
  • processing unit 134 may be electrically connected to electrical stimulator device 132 via a wireless connection or utilizing respective electrically conductive wire 136.
  • processing unit 124 may include a memory having processor-readable instructions stored therein and a processor.
  • an exemplary processor may be utilized to access an exemplary memory and execute exemplary processor-readable instructions.
  • executing exemplary processor-readable instructions by an exemplary processor may configure an exemplary processor to perform a method.
  • an exemplary method may include applying a therapeutical treatment to an exemplary plurality of target cells inside an exemplary living body by electrically stimulating an exemplary plurality of target cells.
  • an exemplary method may include at least one of treating an exemplary plurality of target cells, ablating an exemplary plurality of target cells, delivering a drug or therapeutical substance to an exemplary plurality of target cells, and combinations thereof by electroporation an exemplary plurality of target cells.
  • FIG. 2 shows a method 200 for electroporation of an exemplary plurality of target cells, consistent with one or more exemplary embodiments of the present disclosure.
  • method 200 may include putting tubular probe 100 in contact with an exemplary target region of an exemplary living body containing an exemplary plurality of target cells (step 202) and inducing electroporation to an exemplary plurality of target cells by generating an exemplary pulsed electric field between at least two electrodes of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof of tubular probe 100 inside an exemplary target region (step 204).
  • method 200 may be carried out utilizing tubular probe 100 and system 130. So, method 200 may be described herein below in connection with FIGs. 1A-1E.
  • tubular probe 100 may be put in contact with an exemplary target region of an exemplary living body, where an exemplary target region may contain an exemplary plurality of target cells.
  • an exemplary target region may include an internal region inside an exemplary living body.
  • an exemplary target region and/or an access path thereto may include a tubularshaped or cavity-shaped area inside an exemplary living body.
  • an exemplary target region may include at least one of rectum, vagina, colon, esophagus, tracheal, artery, vein, intestine, stomach, bladder, anus entrance, a narrow space inside at least one of digestive, respiratory, urogenital organs, or vessels, and combinations thereof.
  • putting tubular probe 100 in contact with an exemplary target region of an exemplary living body may include inserting tubular probe 100 into an exemplary living body in the vicinity of an exemplary target region.
  • putting tubular probe 100 in contact with an exemplary target region of an exemplary living body may include inserting tubular probe 100 into an exemplary living body inside an exemplary target region.
  • putting tubular probe 100 in contact with an exemplary target region of an exemplary living body may include placing a portion of tubular probe 100 including at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof in the vicinity of or inside an exemplary target region.
  • putting tubular probe 100 in contact with an exemplary target region may include placing tubular probe 100 in the vicinity or in contact with an exemplary plurality of target cells to be treated.
  • putting tubular probe 100 in contact with an exemplary target region may include sweeping or scanning an exemplary target region by tubular probe 100 via moving proximal end 102b while conducting step 204 of method 200.
  • step 204 may include inducing electroporation to an exemplary plurality of target cells by generating an exemplary pulsed electric field between at least two electrodes of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof of tubular probe 100 inside an exemplary target region.
  • step 204 may include inducing electroporation to an exemplary plurality of target cells by generating an exemplary pulsed electric field between at least two electrodes of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof of tubular probe 100 inside an exemplary target region via applying at least one sequence of electric voltage pulses between exemplary at least two electrodes utilizing electrical pulse generator 132.
  • step 204 may include applying at least one sequence of electric voltage pulses between at least two exemplary electrodes 104a and 104b of first set of electrodes 104 and/or at least two exemplary electrodes 108a and 108b of second set of electrodes 108.
  • applying at least one sequence of electric voltage pulses between at least two exemplary electrodes 104a and 104b (and/or two exemplary electrodes 108a and 108b) may include applying at least one sequence of eight square-wave electric voltage pulses with a magnitude in a range of about 500 V/cm to about 1500 V/cm and a duration of about 100 ps between at least two exemplary electrodes 104a and 104b (and/or two exemplary electrodes 108a and 108b).
  • applying at least one sequence of electric voltage pulses between at least two exemplary electrodes 104a and 104b (and/or two exemplary electrodes 108a and 108b) may include applying at least one sequence of eight square-wave electric voltage pulses with a magnitude of about 1000 V/cm and a duration of about 100 ps between at least two exemplary electrodes 104a and 104b (and/or two exemplary electrodes 108a and 108b).
  • step 204 may further include generating an exemplary pulsed electric field all over an exemplary target region; allowing for electroporation of all exemplary target cells therein.
  • step 204 may further include generating an exemplary pulsed electric field between every two electrodes of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof by generating an exemplary pulsed electric field between every possible pair of electrodes of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof.
  • generating an exemplary pulsed electric field between every two electrodes of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof may include generating an exemplary pulsed electric field in a plurality of directions in an exemplary target region; thereby, resulting in electrical stimulation of all parts of an exemplary target region.
  • generating an exemplary pulsed electric field between every two electrodes of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof may include periodically changing a connection of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof to two poles 132a and 132b of electrical pulse generator 132.
  • periodically changing an exemplary connection of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof to two poles 132a and 132b of electrical pulse generator 132 may include periodically substituting connection of at least one electrode of at least two electrodes 104a and 104b by a different electrode 104c of first set of electrodes 104.
  • substituting connection of at least one electrode of at least two electrodes 104a and 104b by different electrode 104c of first set of electrodes 104 may include electrically disconnecting an exemplary at least one electrode (e.g., 104a) of at least two electrodes 104a and 104b from first pole 132a of electrical pulse generator 132 and electrically connecting different electrode 104c of plurality of electrodes 104 to first pole 132a of electrical pulse generator 132.
  • an exemplary at least one electrode e.g., 104a
  • periodically changing an exemplary connection of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof to two poles 132a and 132b of electrical pulse generator 132 may include stepwise changing an exemplary connection of at least one of first set of electrodes 104, second set of electrodes 108, and combinations thereof to two poles 132a and 132b of electrical pulse generator 132 during a plurality of time steps.
  • each time step of an exemplary plurality of time steps may include a time interval between about 0.5 second and about 5 seconds.
  • method 200 may be performed for a pre-determined period of time until a therapeutical target, for example, complete destruction of an exemplary plurality of cells including a plurality of cancer cells may be achieved.
  • a therapeutical target for example, complete destruction of an exemplary plurality of cells including a plurality of cancer cells may be achieved.
  • an exemplary pre-determined period of time may depend on an exemplary therapeutical target.
  • an exemplary pre-determined period of time may depend on at least one of a location of an exemplary target region, a number of electrodes of first set of electrodes 104 and second set of electrodes 108, an intensity of an exemplary generated pulsed electric field among first set of electrodes 104, and/or second set of electrodes 108, and combinations thereof.
  • an exemplary pre-determined period of time may include a continuous time interval or a plurality of intermittent time intervals.
  • an exemplary pre-determined period of time may include an exemplary plurality of time steps. For instance, for ECT, treatment duration cannot be more than about 20 minutes in each treatment session due to a decrease in concentration of an applied chemotherapeutic in whole bloodstream.
  • method 200 may further include a step of injecting a drug or a therapeutical substance from a reservoir embedded in tubular probe 100 or using an injection syringe into a location in the vicinity of an exemplary zone containing an exemplary plurality of cells.
  • an exemplary injected drug or therapeutical substance may penetrate into electroporated exemplary plurality of target cells; thereby, resulting in treating an exemplary plurality of target cells.
  • FIG. 3 shows an example computer system 300 in which an embodiment of the present disclosure, or portions thereof, may be implemented as computer-readable code, consistent with one or more exemplary embodiments of the present disclosure.
  • computer system 300 may include an example of processing unit 134, and step 204 of flowchart presented in FIG. 2 may be implemented in computer system 300 using hardware, software, firmware, tangible computer readable media having instructions stored thereon, or a combination thereof and may be implemented in one or more computer systems or other processing systems.
  • Hardware, software, or any combination of such may embody any of the modules and components in FIGs. IE and 2.
  • programmable logic may execute on a commercially available processing platform or a special purpose device.
  • One ordinary skill in the art may appreciate that an embodiment of the disclosed subject matter can be practiced with various computer system configurations, including multi-core multiprocessor systems, minicomputers, mainframe computers, computers linked or clustered with distributed functions, as well as pervasive or miniature computers that may be embedded into virtually any device.
  • a computing device having at least one processor device and a memory may be used to implement the above-described embodiments.
  • a processor device may be a single processor, a plurality of processors, or combinations thereof.
  • Processor devices may have one or more processor “cores”.
  • Processor device 304 may be a special purpose or a general -purpose processor device. As will be appreciated by persons skilled in the relevant art, processor device 304 may also be a single processor in a multi-core/multiprocessor system, such system operating alone, or in a cluster of computing devices operating in a cluster or server farm. Processor device 304 may be connected to a communication infrastructure 306, for example, a bus, message queue, network, or multi-core message-passing scheme.
  • computer system 300 may include a display interface 302, for example a video connector, to transfer data to a display unit 330, for example, a monitor.
  • Computer system 300 may also include a main memory 308, for example, random access memory (RAM), and may also include a secondary memory 310.
  • Secondary memory 310 may include, for example, a hard disk drive 312, and a removable storage drive 314.
  • Removable storage drive 314 may include a floppy disk drive, a magnetic tape drive, an optical disk drive, a flash memory, or the like. Removable storage drive 314 may read from and/or write to a removable storage unit 318 in a well-known manner.
  • Removable storage unit 318 may include a floppy disk, a magnetic tape, an optical disk, etc., which may be read by and written to by removable storage drive 314.
  • removable storage unit 318 may include a computer usable storage medium having stored therein computer software and/or data.
  • secondary memory 310 may include other similar means for allowing computer programs or other instructions to be loaded into computer system 300.
  • Such means may include, for example, a removable storage unit 322 and an interface 320. Examples of such means may include a program cartridge and cartridge interface (such as that found in video game devices), a removable memory chip (such as an EPROM, or PROM) and associated socket, and other removable storage units 322 and interfaces 320 which allow software and data to be transferred from removable storage unit 322 to computer system 300.
  • Computer system 300 may also include a communications interface 324. Communications interface 324 allows software and data to be transferred between computer system 300 and external devices.
  • Communications interface 324 may include a modem, a network interface (such as an Ethernet card), a communications port, a PCMCIA slot and card, or the like.
  • Software and data transferred via communications interface 324 may be in the form of signals, which may be electronic, electromagnetic, optical, or other signals capable of being received by communications interface 324. These signals may be provided to communications interface 324 via a communications path 326.
  • Communications path 326 carries signals and may be implemented using wire or cable, fiber optics, a phone line, a cellular phone link, an RF link or other communications channels.
  • computer program medium and “computer usable medium” are used to generally refer to media such as removable storage unit 318, removable storage unit 322, and a hard disk installed in hard disk drive 312.
  • Computer program medium and computer usable medium may also refer to memories, such as main memory 308 and secondary memory 310, which may be memory semiconductors (e.g. DRAMs, etc.).
  • Computer programs are stored in main memory 508 and/or secondary memory 310. Computer programs may also be received via communications interface 324. Such computer programs, when executed, enable computer system 300 to implement different embodiments of the present disclosure as discussed herein. In particular, the computer programs, when executed, enable processor device 304 to implement the processes of the present disclosure, such as the operations in method 200 illustrated by FIG. 2, discussed above. Accordingly, such computer programs represent controllers of computer system 300. Where an exemplary embodiment of method 200 is implemented using software, the software may be stored in a computer program product and loaded into computer system 300 using removable storage drive 314, interface 320, and hard disk drive 312, or communications interface 324.
  • Embodiments of the present disclosure also may be directed to computer program products including software stored on any computer useable medium. Such software, when executed in one or more data processing device, causes a data processing device to operate as described herein.
  • An embodiment of the present disclosure may employ any computer useable or readable medium. Examples of computer useable mediums include, but are not limited to, primary storage devices (e.g., any type of random access memory), secondary storage devices (e.g., hard drives, floppy disks, CD ROMS, ZIP disks, tapes, magnetic storage devices, and optical storage devices, MEMS, nanotechnological storage device, etc.).
  • An exemplary probe disclosed herein has a tubular shape allowing for non-invasive access to internal parts of body, especially, hard to access areas, such as abdominal cavity.
  • Exemplary probe, system, and method disclosed here can be used for in-vivo electroporation of a plurality of target cells in sensitive and/or difficult-to-access regions of a living body, such as cancer cells of an internal tumor or cancer cells remained in margins of a resected tumor.
  • an exemplary probe Using an exemplary probe, limited areas inside a living body can be exposed to an electric field (e.g., a pulsed electric field) by applying an electrical signal to electrodes of an exemplary probe when is inserted into an exemplary target region.
  • An exemplary probe is made of a silicone tube with conductive electrodes in at least two forms of rings there around and/or flat wires at front surface of an exemplary silicone tube.
  • An exemplary probe is suitable for use in cases where an infection or cancer cells are in inner walls of rectum or vagina.
  • an exemplary probe can be efficient for colon cancers in any cases where a patient needs electroporation.
  • colon wall can be subjected to electrochemotherapy by inserting exemplary probe into abdominal cavity from lumen area.

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Electrotherapy Devices (AREA)

Abstract

L'invention concerne une sonde tubulaire pour la stimulation électrique non invasive de cellules cibles dans une région cible interne d'un corps vivant. La sonde tubulaire comprend un tube de support, un premier ensemble d'électrodes comprenant une pluralité d'anneaux circonférentiels positionnés autour du tube de support dans une relation espacée sur le plan axial le long du tube de support, un second ensemble d'électrodes montées sur une partie de tête fixée à une extrémité distale du tube de support, et une pluralité de connecteurs électriques reliant les premier et second ensembles d'électrodes à un dispositif de stimulation électrique. Le second ensemble d'électrodes comprend au moins deux fils en forme de U faisant saillie séparément de la partie de tête Les premier et second ensembles d'électrodes sont placés à l'intérieur de la région cible interne, un champ électrique y étant généré en raison de signaux électriques transférés par l'intermédiaire des premier et second ensembles d'électrodes dans la région cible interne.
PCT/IB2023/062473 2023-12-11 2023-12-11 Électroporation/électrochimiothérapie de régions internes faiblement infectées Pending WO2025125853A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN208782095U (zh) * 2018-10-26 2019-04-23 东莞市星全工业有限公司 一种高频用探针式电连接器
US20230285075A1 (en) * 2017-05-12 2023-09-14 St. Jude Medical, Cardiology Division, Inc. Electroporation systems and catheters for electroporation systems

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230285075A1 (en) * 2017-05-12 2023-09-14 St. Jude Medical, Cardiology Division, Inc. Electroporation systems and catheters for electroporation systems
CN208782095U (zh) * 2018-10-26 2019-04-23 东莞市星全工业有限公司 一种高频用探针式电连接器

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