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WO2025160398A2 - Appareils, systèmes et procédés de commande de distribution d'énergie à un tissu comprenant des exemples de forme d'onde - Google Patents

Appareils, systèmes et procédés de commande de distribution d'énergie à un tissu comprenant des exemples de forme d'onde

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Publication number
WO2025160398A2
WO2025160398A2 PCT/US2025/012956 US2025012956W WO2025160398A2 WO 2025160398 A2 WO2025160398 A2 WO 2025160398A2 US 2025012956 W US2025012956 W US 2025012956W WO 2025160398 A2 WO2025160398 A2 WO 2025160398A2
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WO
WIPO (PCT)
Prior art keywords
electrodes
segments
voltage
pulses
examples
Prior art date
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Pending
Application number
PCT/US2025/012956
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English (en)
Other versions
WO2025160398A3 (fr
Inventor
Kenneth AYCOCK
Timothy O'brien
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Intuitive Surgical Operations Inc
Original Assignee
Intuitive Surgical Operations Inc
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Publication date
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Publication of WO2025160398A2 publication Critical patent/WO2025160398A2/fr
Publication of WO2025160398A3 publication Critical patent/WO2025160398A3/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
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A61B18/1492—Probes or electrodes therefor having a flexible, catheter-like structure, e.g. for heart ablation
    • 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
    • A61B2018/00214—Expandable means emitting energy, e.g. by elements carried thereon
    • 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
    • A61B2018/00482—Digestive system
    • A61B2018/00494—Stomach, intestines or bowel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
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    • 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
    • A61B2018/00577—Ablation
    • A—HUMAN NECESSITIES
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    • A61B2018/00696—Controlled or regulated parameters
    • A61B2018/0075—Phase
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    • A61B2018/00767—Voltage
    • 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
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206—Generators therefor
    • A61B2018/124—Generators therefor switching the output to different electrodes, e.g. sequentially
    • A—HUMAN NECESSITIES
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    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206—Generators therefor
    • A61B2018/1246—Generators therefor characterised by the output polarity
    • A61B2018/1253—Generators therefor characterised by the output polarity monopolar
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    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206—Generators therefor
    • A61B2018/1246—Generators therefor characterised by the output polarity
    • A61B2018/126—Generators therefor characterised by the output polarity bipolar
    • A—HUMAN NECESSITIES
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    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206—Generators therefor
    • A61B2018/1266—Generators therefor with DC current output
    • A—HUMAN NECESSITIES
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    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A61B2018/1405—Electrodes having a specific shape
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    • A—HUMAN NECESSITIES
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    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A61B2018/1405—Electrodes having a specific shape
    • A61B2018/142—Electrodes having a specific shape at least partly surrounding the target, e.g. concave, curved or in the form of a cave
    • 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
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A61B2018/1467—Probes or electrodes therefor using more than two electrodes on a single probe
    • 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
    • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
    • A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
    • A61N1/303—Constructional details
    • A61N1/306—Arrangements where at least part of the apparatus is introduced into the body
    • 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

Definitions

  • the present disclosure relates generally to the energy delivery to tissue.
  • Examples of endoluminal ablation for tissue treatment are described, including the use of cycled energy’ delivery for tissue ablation using electroporation.
  • Ablation-based modalities for eradication of diseased tissue are becoming increasingly popular.
  • Several of such ablation modalities are based on delivery' of electrical energy through tissue to achieve a desired biological effect such as electroporation, electrolysis, or Joule heating.
  • delivering electrical energy throughout the tissue can cause stimulation of nearby excitable cells such as skeletal muscle and nerves.
  • Direct stimulation of skeletal muscle results in contraction, while stimulation of sensory nerves can also result in stimulation (and contraction) of muscle through sensory feedback, as well as pain.
  • pain can be the result of direct stimulation of nociceptors - specialized neurons responsible for the sensation of pain - as well as a secondary result of overstimulation of skeletal muscle.
  • the inner diameter (ID) of the small bowel can vary by approximately 10-15 mm, or even more. These numbers extend even further between different patients.
  • the observed ID of the small bowels across patients can varv from 17 mm to 40 mm.
  • An example apparatus includes an end-effector including at least one electrode and a waveform generator coupled to the endeffector, the waveform generator configured to provide a waveform for electrolytic electroporation.
  • the waveform may include a first portion having a magnitude and duration selected to induce electroporation of tissue and a second portion, following the first portion, having a magnitude and duration selected to generate electrolysis products.
  • the apparatus may include one or more first capacitors configured to be charged to an initial voltage and allowed to discharge to a starting voltage for the second portion, and one or more second capacitors configured to be charged to the starting voltage and allowed to discharge.
  • the waveform generator may include one or more capacitors configured to provide an exponential decaying waveform through a resistive load upon being charged.
  • the waveform generator may include one or more switches configured to open or close a circuit used to discharge one or more capacitors to provide the waveform having sub-pulses, each of which has a magnitude equal to a respective portion of the exponential decay waveform.
  • the waveform generator includes one or more switches, and the waveform generator is configured to control the switches to alternate a polarity of the pulses to provide biphasic pulses.
  • the first portion of the waveform may include biphasic pulses of at least 100V.
  • the second portion of the waveform may include a pulse of less than 50V.
  • the biphasic pulses have a DC offset.
  • the second portion of the waveform includes a sine wave having a magnitude of less than 50V.
  • the waveform generator may be configured to provide the waveform is responsive to an indication of a refractory period in a cardiac cycle.
  • An example method may include providing a waveform for electrolytic electroporation, the waveform including a first portion having a magnitude and duration selected to induce electroporation of tissue, and a second portion, following the first portion, having a magnitude and duration selected to generate electrolysis products.
  • the magnitude of the first portion is greater than the magnitude of the second portion.
  • each portion of the first and second portions includes a square wave, and the first portion and the second portion are continuous.
  • providing the waveform includes providing an exponential decaying waveform through a resistive load upon being charged.
  • the second portion of the waveform may include a decay longer than a decay of the first portion.
  • the first portion and the second portion of the waveform are discontinuous.
  • the first portion of the waveform includes biphasic pulses of at least 100V.
  • the biphasic pulses have a DC offset.
  • the second portion of the waveform includes a pulse of less than 50V.
  • the second portion of the waveform comprises a sine wave having a magnitude of less than 50V.
  • providing the waveform is responsive to an indication of a refractory period in a cardiac cycle.
  • An example apparatus includes a flexible circuit and generator circuitry coupled to the flexible circuit.
  • the flexible circuit is configured to be disposed in proximity' with a treatment region.
  • the flexible circuit includes multiple segments of electrodes, each segment of the multiple segments including a respective first and second electrode.
  • the generator circuitry individually energizes electrodes of the multiple segments.
  • the generator circuitry utilizes pulsed electric fields to control activation of selected segments of electrodes of the multiple segments of electrodes in order to control an amount of energy applied to the treatment region below an energy threshold for muscle stimulation.
  • the first electrode and the second electrode are an anode and a cathode, respectively.
  • the first electrode and the second electrode are respectively configured as an anode and a cathode at a first time period and wherein the first electrode and the second electrode are respectively configured as a cathode and an anode at a second time period.
  • the generator circuitry sequentially energizes selected one or more segments. In some example apparatuses, the generator circuitry' energizes a subset of segments of electrodes in proximity to the treatment region without energizing the other segments of electrodes among the segments of electrodes. In some example apparatuses, the generator circuitry' energizes each segment of electrodes in proximity to the treatment region without energizing the other segments of electrodes among the segments of electrodes.
  • the generator circuitry provides bipolar control and monopolar control to the segments of electrodes at different time periods, wherein electrodes of the segments of electrodes receive different polarities of voltage or current at time periods during the bipolar control, each electrode of the segments of electrodes receives a same polarity of voltage or current during the monopolar control.
  • the generator circuitry' includes an H-bridge circuit configured to provide monopolar or bipolar voltages to each electrode of the segments of electrodes.
  • the generator circuitry provides biphasic delivery by controlling two levels of applied voltages.
  • the generator circuitry provides an exponential pulse.
  • selected segments of electrodes include adjacent segments of electrodes, wherein different combinations of adjacent segments of electrodes are selected alternatively in a sequence.
  • each segment of electrodes is activated an arbitrary number of times (e g., twice) in succession.
  • An example system includes a signal generator configured to couple to multiple electrode segments disposed adjacent target tissue and a controller coupled to the signal generator.
  • the controller controls the signal generator to provide signals to selected ones of the electrode segments, and provides control signals to the signal generator to generate a first set of voltage or current pulses for a first electrode segment of the multiple electrode segments and a second set of voltage or current pulses for a second electrode segment of the multiple electrode segments, after generation of the first set of voltage or current pulses, wherein a magnitude, duration, and number of the first and second set of voltage or current pulses are configured to deliver energy to the target tissue to generate electroporation while reducing energy, reducing stimulation, and/or maintaining the energy below a threshold for muscle stimulation.
  • the first set of voltage or current pulses and the second set of voltage or current pulses are subsets of voltage or current pulses, and the controller provides control signals to the signal generator to repeat a sequence of generating the first and second set of voltages or current pulses for the first and second electrode segments until a full set of voltages or current pulses are provided to the first and second electrode segments.
  • the first set of voltage or current pulses and the second set of voltage or current pulses are sets of voltage or current pulses configured to complete a treatment.
  • the generator circuitry provides bipolar control and monopolar control, wherein certain electrodes of the multiple electrode segments receive different polarities of voltage or current at different time periods during the bipolar control, and each electrode of multiple electrode segments receives a same polarity 7 of voltage or current during the monopolar control.
  • the controller further determines a number of electrode segments exposed in proximity to the target tissue and selects one or more segments from the number of electrode segments exposed in proximity to the target tissue.
  • An example method may include positioning segments of independently-addressable electrodes adjacent a circumference of target tissue such that a first segment through a final segment span the circumference, delivering energy to a portion of the target tissue through a first segment of electrodes during a time period other electrodes are not delivering energy, wherein the energy is below a threshold for muscle stimulation, after said delivering energy 7 through the first segment of electrodes, delivering energy to another portion of the target tissue through a second segment of electrodes, and after said delivering energy through the second segment of electrodes, sequentially delivering energy through additional segments of electrodes until the final segment of electrodes is used.
  • said delivering energy includes delivering a subset of pulses to the first segment through final segment, and repeating delivering the subset of pulses to the first through final segments until all subsets of pulses for a treatment are delivered.
  • Some example methods further include receiving information about impedance or circumference to determine the number of segments in the first segment through final segment.
  • Some example methods further include delivering energy in a bipolar and monopolar manner, wherein delivering energy in the bipolar manner comprises providing different polarities of voltages or currents at time periods to certain electrodes of each segment among the first through the final segments of electrodes, and wherein delivering energy in the monopolar manner comprises providing same polarity of voltage or current to each electrode of each segment among the first through the final segments of electrodes.
  • An example method may include delivering a first at least one voltage or current pulse to a bipolar configuration of electrodes to deliver energy to a treatment region, the first at least one voltage or current pulse selected to cause electroporation of tissue in at least a portion of the treatment region, and delivering a second at least one voltage or current pulse to a monopolar configuration of electrodes to deliver energy to the treatment region, the second at least one voltage or current pulse selected to cause electrolysis, electrophoresis, or both, proximate to the treatment region, wherein energy delivered using the second at least one voltage or current pulse is below a threshold for muscle stimulation.
  • the at least one of the bipolar configuration of electrodes and the monopolar configuration of electrodes comprises segments of electrodes, and in each delivery of first or second voltage or current pulses, the voltage or current pulses are delivered to one or more segments among the segments of electrodes.
  • said delivering the first at least one voltage or current pulse to the bipolar configuration of electrodes includes delivering the first at least one voltage or current pulse of first polarity to the bipolar configuration of electrodes, and delivering the first at least one voltage or current pulse of second polarity’ different from the first polarity to the bipolar configuration of electrodes.
  • said delivering the first at least one voltage or current pulse to the bipolar configuration of electrodes includes all segments of electrodes, wherein said delivering the second at least one voltage or current pulse to the monopolar configuration of electrodes includes one or more segments of electrodes at time, and wherein the said delivering the second at least one voltage or current pulse is repeated until all the segments are delivered the second at least one voltage or current pulse.
  • FIG. 1A is a schematic diagram of an ablation system according to some examples.
  • FIG. IB is a schematic diagram of an ablation device in the ablation system according to some examples.
  • FIG. 2A is a schematic diagram of an ablation device according to some examples.
  • FIG. 2B is a schematic diagram of an activation sequence of segments of electrodes according to some examples.
  • FIG. 3 shows perspective and cross-section schematic illustrations showing delivery of energy by an ablation device, according to some examples.
  • FIG. 4 shows cross-section schematic illustrations of the ablation device deployed in expanded configurations, according to some examples.
  • FIG. 5A is a flow chart of a method of energy delivery using an ablation device, according to some examples.
  • FIG. 5B is a flow chart of a method of energy delivery using an ablation device, according to some examples.
  • FIG. 5C is a flow chart of a method of energy delivery using an ablation device, according to some examples.
  • FIG. 5D is a flow chart of a method of energy delivery using an ablation device, according to some examples.
  • FIG. 5E is a flow chart of a method of energy delivery using an ablation device, according to some examples.
  • FIG. 6A illustrates schematic graphs showing relationships between a numbers of pulses and acceleration magnitudes in examples of conventional ablation systems.
  • FIG. 6B illustrates schematic graphs showing relationships between a numbers of pulses and acceleration magnitudes in examples of ablation systems described herein.
  • FIG. 7 is a table showing relationships between treatment sites, experimental conditions, and results in examples of systems described herein.
  • FIG. 8A is a cross-section of an ablation site of a small intestine of a pig after ablation using a conventional ablation system.
  • FIG. 8B is a cross-section of an ablation site of a small intestine of a pig after ablation using an example ablation system described herein.
  • FIG. 9 is a schematic diagram of an example of generator circuitry according to some examples.
  • FIG. 10A is a schematic diagram of electrodes functioning as anodes and cathodes according to examples described herein.
  • FIG. 10B is a schematic diagram of electrodes functioning as anodes and cathodes according to examples described herein.
  • FIG. 10C is a schematic diagram of electrodes functioning as anodes and cathodes according to examples described herein.
  • FIG. 11 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 12 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 13 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 14 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 15 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 16 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 17 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 18 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 19 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 20 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • FIG. 21 is a schematic diagram for a robotically-assisted servomechanism system, according to some examples.
  • FIG. 22A is a schematic diagram of an instrument system according to examples described herein.
  • FIG. 22B illustrates a distal portion of the instrument system of FIG. 22A with an extended example of an instrument according to examples described herein.
  • FIG. 23 is a perspective view of a manipulator system according to examples described herein.
  • FIG. 24 is a top view of a manipulator system according to examples described herein. DETAILED DESCRIPTION
  • methods which allow for the delivery of ablative energy while mitigating stimulation of a muscle/nerve may be advantageous.
  • the mitigation, avoidance, and/or minimization of muscle stimulation may reduce pain, make treatments more accessible, and reduce complexity in the delivery of treatment, such as by reducing movement of a treated subject.
  • a self-sizing, endoluminal electrical energy-based ablation system for the small bowel may be advantageous to generate consistent tissue effects across a wide range of diameters.
  • the energy density is a primary determinant of biological effects, which creates a challenge for self-sizing devices.
  • the device may expand less to bring electrodes into proximity with tissue.
  • the diameter may be sufficiently low and may cause high energy densities that could create overtreatment and side effects.
  • the devices may expand more to adjust to the size of the lumen, and lower energy densities may result which could present the risk of undertreating.
  • Examples described herein provide systems, apparatuses and methods that control activation of selected segments of electrodes of an ablation device.
  • Each of the segments of electrodes may ablate each portion of tissue in proximity to each segment instead of the entire tissue of an overall treatment site.
  • energy may be delivered in a segment-based manner.
  • an amount of energy delivered at any given time by ablating one or more portions of tissue an amount of electrical current flowing through the tissue may be lowered, or the energy may be localized to the ablated segment of the tissue and exposure of nerves and/or muscle outside the portion of tissue to electrical signals may be reduced.
  • an amount of muscle stimulation due to current passing through the tissue may be reduced and thermal effects by cycling energy through segments of electrodes may be controlled.
  • ablation devices such as end effectors have a flexible ablation treatment area.
  • devices described herein may control expansion of one or more portions of the ablation device according to a diameter of lumen. Additionally or instead, examples described herein may activate electrodes on a per-segment basis. These features may allow for control of the area and amount of ablation.
  • an ablation device with a flexible circuit may include segments of electrodes that may be individually activated. Examples described herein provide systems, apparatuses and methods that allow for delivery of energy 7 to one or more portions of tissue instead of entire tissue at a time.
  • each electrode segment may include an individually-energizable (e.g., electrically distinct) anode and cathode.
  • all segments may share either an anode or a cathode, where each segment has an individually-addressable cathode or anode, respectively.
  • Each electrode in the segment may itself have multiple conductive members that may extend along a treatment region.
  • each electrode segment may have an interdigitated fork structure, with conductive members of an anode electrode interdigitated with conductive members of a cathode electrode in each segment.
  • segments of electrodes may be disposed in a flexible circuit provided around an expandable member of an elongate flexible device, such as a catheter. Once the expandable member is expanded proximate a treatment region, some or all of the electrode segments may be positioned in contact, or near, the corresponding portions of tissue for treatment.
  • a number of segments that may be positioned to treat the tissue may be dependent on a final diameter of the expanded member in a concentric unwinding electrode arrangement. While planar electrode arrangements will be described as detailed examples herein, a partial or an entire multi-layer electrode structure may be possible. For a rolled electrode arrangement, the segments may be arranged as partial circumferential regions of the full electrode member and/or partial axial regions of the full electrode member.
  • Examples described herein include control techniques for providing cycled energy 7 for ablation using segmented electrode structures.
  • generator circuitry may provide cycled energy 7 for segments of electrodes.
  • the generator circuitry may include a signal generator and switching structure. The switching structure may allow a generator output to be switched to segmented electrodes.
  • the generator circuitry may include specialized generators that may generate segmented, cycled energy signals themselves. A variety of control schemes for use of segmented electrodes may provide target energy to a localized treatment area.
  • pulses used to treat the tissue may be provided using one or more segments activated in the treatment area, without activating other segments to suppress providing energy to areas outside the target treatment area of the tissue and/or to limit a total amount of energy supplied to the target treatment area at a given time. Then, pulses may be delivered to other segments. In one example, all pulses to be used for treatment may be provided to a first segment, then all pulses provided to a second segment, and then to further segments until all segments used for treatment have been used to deliver the treatment energy.
  • a subset of pulses to be used for treatment may be provided to a first segment, then a subset of pulses provided to a second segment, and then to further segments until all segments used for treatment have been used to deliver the subset of pulses. Then the first segment may again be used to deliver another subset of pulses, followed by the second segment, and then further segments until all segments used for treatment have been used to deliver the next subset of pulses. This process may be repeated until all subsets of pulses to be used for treatment have been delivered.
  • combinations of segments may be used to deliver pulses and/or subsets of pulses. In some examples, selecting a number of segments to be used may be based on lumen diameter.
  • monitoring impedance at the segments and/or a volume of the expandable member and/or a visual indication of catheter diameter with regards to the lumen may be performed to determine a number of segments that are likely in contact with, or sufficiently near, tissue to be treated. The number of segments may then be used to deliver treatment energy.
  • the segmented electrode structures and control techniques may advantageously reduce deleterious muscle stimulation.
  • the muscle stimulation may be due to depolarization of skeletal muscle cells during ablation treatment, such as neural feedback and/or direct depolarization of muscle cells due to electrical stimulus and/or stimulation of sensory nerves.
  • the reduced energy delivery to the treatment area may be performed in any particular time window, because only selected segments are energized in any particular time window.
  • muscle contraction to be induced may be limited to a tentative level or no contraction.
  • Examples described herein include control techniques for providing cycled energy for ablation using a combined bipolar/monopolar technique.
  • a shorter, higher-magnitude pulse may be delivered using a bipolar, biphasic configuration at parameters to cause electroporation of target tissue (e.g., to cause reversible electroporation for permeabilization of cell membranes in the target tissue in some examples).
  • One or more lower-magnitude pulses with a relative long total duration may then be delivered.
  • the one or more lower-magnitude pulses may include a long pulse.
  • the one or more lower-magnitude pulses may include a series of short pulses.
  • the one or more lower- magnitude pulses may be delivered using a monopolar configuration at parameters to cause electrolysis and/or electrophoresis (e.g., to cause the products of electrolysis and/or electrophoresis to cause treatment to the permeabilized cells in some examples).
  • delivery of energy during the monopolar application of energy may be sufficiently low to avoid the detrimental effects of monopolar energy delivery (e.g., muscle stimulation).
  • the bipolar/monopolar technique could be implemented in conjunction with segmented electrodes. For example, all segments may be used to deliver the bipolar, biphasic pulses for electroporation, and then the monopolar pulse(s) may be delivered in a segmented manner.
  • the biphasic pulses may include a biphasic square pulse, or an asymmetric biphasic square pulse where one polarity has a different amplitude than the other polarity.
  • an amount of current passing through tissue may be reduced, as an area or a spatial location of the current within tissue is controlled by segment control and pulse control.
  • a risk of overstimulating excitable cells, such as nerves and muscles, may be reduced and thermal effects may be controlled.
  • a flexible circuit including segments of electrodes on an expandable member may allow for control of a treatment area, and thus may improve the consistency of treatment across variable anatomical sizes and spatially customized treatment may be obtained. Together with monopolar/bipolar pulse control, electroporation and electrolysis and/or electrophoresis may be controlled.
  • monitoring impedance at the segments may improve resolutions of bioimpedance data within a tissue target, and increase the resolution and feasibility' of impedance sensing.
  • FIG. 1A is a schematic diagram of an ablation system 100 according to some examples.
  • the ablation system 100 includes generator circuitry 101, controller 104, ablation device 120, an elongate flexible device 130, and power supply 102.
  • the generator circuitry' 101 includes signal generator 1011 and switches 1013.
  • the controller 104 includes processor(s) 106 and computer readable media 108.
  • the computer readable media 108 include executable instructions for generating pulses 110, executable instructions for selecting segments 112, and parameters 114.
  • FIG. IB is a schematic diagram including an ablation device arranged in accordance with examples described herein.
  • FIG. IB includes elongate flexible device 130 and ablation device 120.
  • the elongate flexible device 130 includes one or more sensors 18.
  • the one or more sensors 18 may be implemented as part of the elongate flexible device 130, as part of the ablation device 120, and/or as part of a separate instrument.
  • the ablation device 120 includes expandable member 14, flexible circuit 15, multiple segments of electrodes 16 including electrode segments 161, 162, 163, and 164.
  • the ablation device 120 of FIG. IB may be used to implement and/or may be implemented by the ablation device 120 of FIG. 1A.
  • other elements with like reference numbers to FIG. 1A may be used to implement and/or be implemented by the components of FIG. 1A.
  • FIG. IB The components of FIG. IB are exemplary 7 . Additional, fewer, and/or different components may be used in examples.
  • Examples of ablation devices described herein may include a flexible circuit, such as the ablation device 120 including a flexible circuit 15.
  • the flexible circuit may be formed, for example, from a flexible substrate and electrodes (e.g., conductive traces) supported by the substrate.
  • the flexible circuit 15 may be composed of biocompatible materials with flexibility. In this manner, the flexible substrate may be expanded, contracted, rolled, unrolled, and/or otherwise manipulated during operation in some examples.
  • the flexible circuit 15 may be disposed in proximity 7 with a treatment region during operation of the ablation system.
  • the flexible circuit 15 includes multiple segments of electrodes 16. Each segment of the multiple segments of electrodes 16 may include one or more different sets of electrodes that may function as different polarities, such as anodes and cathodes.
  • a segment of electrodes may refer to one or more electrodes that may be addressed (e.g., energized) together and independently of other segments.
  • a segment of electrodes may in some examples include 2 electrodes, although in some examples a segment may include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more electrodes.
  • the segments of electrodes may be coupled to the generator circuitry 7 101.
  • a set of electrodes may be activated by a positive voltage supplied from the generator circuitry 101 to function as anodes.
  • a set of electrodes may be activated by a negative voltage supplied from the generator circuitry 101 to function as cathodes.
  • the ablation device 120 may optionally include one or more expandable members 14. such as balloons.
  • the flexible circuit 15 including segments of electrodes 16 may be disposed on or in the expandable member 14.
  • the segments of electrodes 16 may surround the expandable member 14.
  • the expandable member 14 may be used to provide an outward tissue apposition force to the segments of electrodes 16. In this manner, expansion of the expandable member may ensure sufficient contact between the segments of electrodes 16 and the target tissue for treatment to occur - e.g., for electrolysis products to diffuse into the target tissue.
  • Examples of ablation devices described herein may be provided in and/or delivered by an elongate flexible device, such as the elongate flexible device 130 of FIG. IB.
  • the elongate flexible device 130 may be implemented by a manual guidewire catheter actuated by hand.
  • the elongate flexible device 130 may be implemented using a flexible catheter, endoscope, duodenoscope, or other device that is robotically driven, for example by a robotically-assisted servomechanism system.
  • the ablation device 120 may be implemented using an end effector for a flexible ablation instrument that extends through a working channel of the elongate flexible device 130 or along the elongate flexible device 130.
  • the ablation device 120 may optionally be a removable attachment that is coupled to a distal end of the elongate flexible device 130.
  • Examples of systems described herein may include generator circuitry, such as generator circuitry 101 of FIG. 1A.
  • the generator circuitry 101 may provide control signals to segments of electrodes described herein.
  • the control signals may be provided to selectively provide cycled energy delivery to tissue, cycled pulsed electric fields in some examples.
  • the generator circuitry' 101 may provide cycled energy' responsive to one or more control signals from the controller 104.
  • the generator circuitry 101 may include a signal generator 1011 and switches 1013.
  • the signal generator 1011 is coupled to multiple segments of electrodes.
  • the switching structure may allow an output of the generator circuitry 101 to be switched to one or more target segments of multiple segments of electrodes.
  • the generator circuitry 101 may include specialized generators that may generate segmented, cycled energy signals themselves instead of using the switches 1013 of FIG. 1A. Accordingly, the switches 1013 may be optional. Manners of selective activation of one or more segments of electrodes may not be limited to the switching structure of FIG. 1A. A variety' of control schemes for use of segmented electrodes may provide target energy to a localized treatment area.
  • the signal generator 1011 may be a pulse generator, which may provide various types and/or patterns of pulses to be provided to one or more segments of the electrodes of the ablation device 120.
  • the signal generator 1011 may provide a pattern of pulses responsive to one or more control signals from the controller 104. Various ty pes of pulses may be used - square pulses, sine wave pulses, exponentially-decaying pulses, or other shapes of pulses.
  • the controller 104 may provide a signal to the signal generator 1011 indicative of a type (e.g., a shape) of pulse.
  • the signal generator 1011 may be implemented using an exponential decay wave generator (by way of example, a Harvard Apparatus BTX 630); however, this disclosure is not limited thereto or thereby.
  • the signal generator 1011 may include a bank of capacitors to select from, as controlled by the controller 104.
  • the signal generator 1011 may allow for selection of a specific charge (e.g., capacitance) per application of the charge.
  • the signal generator 1011 may provide a pattern of pulses responsive to one or more control signals indicative of the pattern of pulses from the controller 104.
  • the patterns may include bipolar or monopolar pulses.
  • the signal generator 1011 may activate pairs of electrodes of selected segments of electrodes 16 with opposite polarities.
  • the bipolar pulse pattern may be used to deliver a high voltage that may result in a high level of current.
  • the generator circuitry may switch polarities between pairs of electrodes in adjacent segments. Thus, the voltage’s polarity to be applied by each segment may alternate.
  • the signal generator 1011 may activate anodes without activating cathodes.
  • one or more return electrodes may be placed outside a surgical field but in contact with the patient (e.g., using a pad having an electrode).
  • one polarity e.g., the polarity of the active electrode
  • the activation of anodes without activation of cathodes may be used to provide a low voltage that results in a low level of current.
  • the generator circuitry 101 may provide biphasic delivery by controlling in two modes - a bipolar and a monopolar control.
  • the higher current bipolar control may be used to generate electroporation to provide openings in cell membranes of target tissue
  • the lower current monopolar control may be used to generate the products of electrolysis to diffuse into the opened cell membranes for treatment.
  • the signal generator 1011 may active electrodes as cathodes. Using electrodes as cathodes may suppress oxidation accumulation on metal surfaces, while using the electrodes as anodes may suppress gas production in tissue. Activation of the electrodes as cathodes may increase a pH level in the vicinity' of the electrodes, while activation of the electrodes as anodes may decrease the pH level. Thus, the pH level over the tissue in the vicinity of the electrodes may be controlled by selecting use of an electrode as a cathode and/or as an anode.
  • Examples of systems described herein may include one or more controllers, such as controller 104 of FIG. 1A.
  • the controller 104 may be coupled to the signal generator 1011 and may control the signal generator 1011 to provide signals to selected ones of the segments of electrodes 1 .
  • the generator circuitry 101 coupled to the flexible circuit 15, may individually energize the selected ones of the segments of electrodes 16.
  • the generator circuitry 101 may utilize pulsed electric fields to control activation of selected ones of the segments of electrodes 16 of the multiple segments of electrodes 16 to control an amount of energy applied to the treatment region below an energy threshold for muscle stimulation.
  • systems described herein may be used to perform treatment to tissue.
  • the treatment may be, for example, tissue ablation.
  • the tissue ablation may be performed using electroporation and/or electrolysis in some examples. If the entire energy to be used for the treatment were delivered to all segments of electrodes (e.g., all segments of electrodes in contact with tissue), the overall energy density delivered may be above a threshold to cause significant muscle stimulation, which may be disadvantageous. Accordingly, examples of systems described herein may deliver the treatment energy 7 in a cycled manner - such as through sequential energizing of electrode segments. In this manner, pulses of voltage and/or current may be delivered to only a portion of the treatment region during a particular time period, and the overall energy density delivered in a particular time period may remain below a threshold for muscle stimulation.
  • the threshold for muscle stimulation described herein refers to a threshold for muscle stimulation which may adversely affect the delivery of the treatment. Energy delivery may be expected to deliver low levels of muscle stimulation, however the threshold described herein refers to a threshold for energy delivery' that may cause muscle stimulation that may result in muscle strains, tears, severe pain, soreness, and/or muscle fatigue, or below a certain magnitude required by some other medical procedures.
  • a semi-quantitative scale can be used to classify and/or grade the intensity of muscle stimulation relative to the observed stimulatory' effect.
  • a first classification, classification 0. may refer to no muscle contractions occurring.
  • a second classification, classification 1, may refer to a twitch of the muscle. For example, muscle twitches may occur without inducing muscle contraction in some examples. Twitches are generally not disruptive to treatment delivery' described herein.
  • a third classification, classification 2, may refer to an unfused tetanus. An unfused tetanus generally refers to muscle contraction that may increase a force of contraction beyond a twitch. The force of contraction may build locally within an affected muscle group.
  • unfused tetanus may be disruptive to treatment, as the muscle contractions, even if occurring with relaxation periods, may result in pain and local movement of the treatment region.
  • a fourth classification, classification 3 may refer to a fused tetanus. In a fused tetanus, the muscle remains contracted and may not relax. Energy delivery to the tissue may be such that relaxation and recovery 7 may not occur.
  • Examples of systems described herein may deliver energy such that the energy delivery in a particular time period results in muscle stimulation in the classification of twitch or less.
  • Unfused tetanus and fused tetanus classifications may be material muscle stimulations, indicating too high of an energy delivery.
  • Examples described herein may deliver a same therapeutic effect while shifting the level of stimulation from a classification 2 into a classification 1. In classification 1, mild stimulation can be observed as twitches in the body wall but generally do not result in gross movement of extremities or the abdomen of patient.
  • muscle stimulation is a complex phenomenon. Without being bound by theory, muscle stimulation can ultimately be considered the result of depolarization of skeletal muscle cells, which results in the initiation of a cascade of events that causes contraction.
  • This depolarization can generally be understood to be achieved via two mechanisms. The first is direct depolarization of muscle cells due to electrical stimulus: in this pathway, the energy delivered may directly cause a biophysical effect on the muscle cells, resulting in contraction.
  • the second is stimulation of sensory' nerves: in this pathway, electrical pulses stimulate nearby neurons, generating an action potential that travels back toward the spinal cord, passes through an interneuron there, and generates a stimulus in a motor neuron. The action potential travels down the motor neuron to a neuromuscular junction near the skeletal muscle fiber(s). Skeletal muscle is then depolarized through a chemical signaling process involving acetylcholine.
  • the intensity of muscle contraction depends on how many nerves are stimulated as well as how' many times each of the nerves are stimulated. This is a mechanism known as force summation. If a small number of nerves are stimulated and they are not stimulated for long enough to generate several action potentials, then the intensity of the contraction of the muscle they innervate will be lower than it would be if more nerves were stimulated for a longer duration.
  • aspects that contribute to muscle stimulation generally include, from an energy/ waveform perspective: electric field amplitude, current amplitude, voltage amplitude, pulse duration, delays within pulses, proximity of treatment to excitable cells (e.g., muscle fibers, sensory neurons), and/or directionality.
  • excitable cells e.g., muscle fibers, sensory neurons
  • directionality e.g., when pulses have a short pulse width, a biphasic waveform may be less stimulatory than a monophasic waveform - e.g..
  • VGSCs voltage-gated sodium channels
  • a higher threshold means a stronger electric field is needed to stimulate the nerve.
  • Excitable cells generally have a characteristic strength-duration curve, which is why reducing pulse width and/or amplitude decreases stimulation.
  • a bipolar electrode configuration is generally less stimulatory than a monopolar electrode configuration - generally because the current path is more localized.
  • the current passes from an end effector and through a patient’s body to a ground/surface electrode in a monopolar configuration, the current passes through the entire body between the energized electrode and the ground electrode, encountering more nerves and more skeletal muscle along the way, increasing opportunities for muscle stimulation.
  • Examples described herein may provide cycled energy delivery to a treatment region so that energy delivered at a particular time does not exceed a threshold for muscle stimulation. This may. for example, reduce the volume of tissue that current is flowing through and/or reduce the gross amount of current passing through the tissue at any given time, which in itself may reduce the likelihood of stimulating excitable cells in the treatment region. Further, cycled energy delivery may reduce the volume of tissue that current is flowing through at a given time.
  • cycled energy delivery may reduce the volume of tissue that current is flowing through at a given time.
  • rheobase current intensity that describes a minimum current needed to generate an action potential in that cell.
  • the energy threshold for muscle stimulation may be determined for a device and/or system described herein.
  • the energy threshold may be specific to a particular treatment region (e.g., bowel or lung).
  • a system may be used in a preclinical assessment of muscle contraction. Different cycle times, patterns, voltage magnitudes, and/or current magnitudes may be applied to tissue using the system, and resulting muscle contractions may be graded into classifications. The resulting muscle contractions may be graded based on visual observation and/or based on measurements from the tissue. For example, an accelerometer may be placed on the patient and/or proximate the tissue.
  • the accelerometer readings may be indicative of muscle contractions and may be used to classify muscle stimulation.
  • a threshold of voltage, current, pulse width, and/or segment size may be determined to retain the energy deliver below a threshold classification of muscle stimulation (e.g., classification one or below).
  • the controller 104 may provide control signals to the signal generator 1011 to generate a set of voltage or current pulses for a segment of the multiple segments of electrodes 16 in the ablation device 120, and another set of voltage or current pulses for another segment of the multiple electrode segments 16. after generation of the set of voltage or current pulses.
  • a magnitude, duration, and number of the sets of voltage or current pulses for delivery of energy to the target tissue are controlled or selected to provide a treatment to the target tissue while maintaining the energy below a threshold for muscle stimulation.
  • the treatment may be an ablation treatment.
  • the ablation treatment may in some examples utilize electroporation and/or electrolysis.
  • a magnitude, duration, and/or number of the sets of voltage or current pulses may be selected to generate electroporation of cells in the tissue (reversible electroporation in some examples).
  • the controller 104 may be programmed to cause the generator circuitry 101 to provide an electronic signal indicative of a dose of the electrolysis products and/or permeability level of a cell.
  • the controller 104 may, for example, include such a program, or include one or more processing devices (e.g., processors) coupled to the computer-readable media 108 encoded with executable instructions. Although shown as a separate component coupled to the ablation device 120 via the elongate flexible device 130, in some embodiments, the controller 104 may be integrated into the ablation device 120. In some embodiments, the controller 104 may include programmable circuitry’ coupled to the ablation device 120. The controller 104 may be coupled by a wire or communicate with the ablation device 120 wirelessly.
  • processing devices e.g., processors
  • the controller 104 may include one or more processor(s) 106, computer-readable media 108 (e.g., memory), and other computing system components, such as one or more input devices, output devices, sensors, and/or communication devices in some examples. Additional, fewer, and/or different components may be used in other examples.
  • the controller 104 may be implemented using a computing device. Examples of computing devices include controllers, microcontrollers, computers, servers, medical devices, smart phones, tablets, wearable devices, and the like. The computing device may be handheld and may have other uses as well.
  • the controller 104 may include one or more processors, such as the processor 106. Any kind or number of processors may be present, including one or more central processing unit(s) (CPUs) and/or graphics processing unit(s) (GPUs) having any number of cores, controllers, microcontrollers, and/or custom circuity such as one or more application specific integrated circuits (ASICs) and/or field programmable gate arrays (FPGAs).
  • processors such as the processor 106. Any kind or number of processors may be present, including one or more central processing unit(s) (CPUs) and/or graphics processing unit(s) (GPUs) having any number of cores, controllers, microcontrollers, and/or custom circuity such as one or more application specific integrated circuits (ASICs) and/or field programmable gate arrays (FPGAs).
  • CPUs central processing unit
  • GPUs graphics processing unit having any number of cores
  • controllers controllers, microcontrollers, and/or custom circuity
  • the controller 104 described herein may include the computer-readable media 108, such as memory. Any type or kind of memory may be present (e.g., read only memory 7 (ROM), random access memory (RAM), solid state drive (SSD), secure digital card (SD card), and the like). While a single box is depicted schematically as the computer-readable media 108 in FIG. 1A, any number of computer-readable media 108 devices may be present.
  • the computer- readable media 108 may be in communication with (e.g., electrically connected to) the processor 106.
  • the computer-readable media 108 may store executable instructions for generating pulses 110 used for electroporation and/or electrolysis with segments of electrodes included in the ablation device 120.
  • executable instructions for generating pulses 110 may include controlling a pattern of pulses by controlling generator circuitry 101 to provide bipolar or monopolar pulses to the one or more segments of electrodes in the ablation device 120.
  • the computer-readable media 108 may store executable instructions for selecting segments 112 used for electroporation and/or electrolysis with electrode segments of electrodes included in the ablation device 120.
  • executable instructions for selecting segments 112 may include controlling the switches 1013 to selectively turn on one or more switches that may couple to corresponding one or more segments of a plurality 7 of segments of electrodes to an output of the signal generator 1011, thus selectively providing an output signal from the signal generator 1011 to activate the one or more segments of electrodes.
  • the switches 1013 may be provided in a switch box and/or may be integrated with other components.
  • the computer-readable media 108 may store parameters 114 that may be selected in the process for controlling one or more segments of electrodes.
  • the parameters 114 may include a duration, a voltage or range of voltages, a number of pulses, a type of pulse, and/or any combination thereof, to be applied on the treated regions based on the degree of ablation to control charge on the one or more electrodes in the ablation device 120.
  • electric field strengths, current levels, capacitance, waveform shapes, etc. may also be selected as the parameters 114.
  • the parameters 114 may be used by the executable instructions for generating pulses 110.
  • the parameters 114 may include an activation sequence of a plurality of segments of electrodes that may be used by the executable instructions for selecting segments 112.
  • the controller 104 may perform the executable instructions for generating pulses 110 and the executable instructions for selecting segments 112 to timely provide various patterns of pulses generated by the signal generator 1011 to selected segments of electrodes 16 coupled to the signal generator 1011 by the switches 1013.
  • the controller 104 may alternate or otherwise select a pattern of activated electrodes (e.g., activating pairs of electrodes in sequence) to shape or deliver a particular electric field.
  • the generator circuitry 101 may sequentially energize selected segments of electrodes 16.
  • ablation treatment may be provided.
  • the ablation may be achieved using electroporation and/or electrolysis.
  • one or more of the electrodes used to apply electroporation may also be used to generate products of electrolysis (e.g., some or all of the electrodes may be used for both electroporation and electrolysis), while in other embodiments, the electrodes used to apply electroporation may be different than the electrodes used to generate products of electrolysis.
  • the controller 104 may also be used to induce a current through the tissue, such as between electrodes, to generate products of electrolysis.
  • the products of electrolysis may cause ablation of the permeabilized cells.
  • a combination of parameters in the parameters 114 may be selected to indicate that all pulses to be used for treatment may be provided to a first segment, then all pulses provided to a second segment, and then to further segments until all segments used for treatment have been used to deliver the treatment energy.
  • a sequence of activation may indicate that segment 1, segment 2, ... , segment N (N: natural number indicative of a number of a plurality of electrodes) may be activated in this order when each segment receives all pulses.
  • segment 1, segment 2, ... , segment N may be aligned in an order.
  • a combination of parameters in the parameters 114 may be selected to indicate that a subset of pulses to be used for treatment may be provided to a first segment, then a subset of pulses provided to a second segment, and then to further segments until all segments used for treatment have been used to deliver the subset of pulses. Then the first segment may again be used to deliver another subset of pulses, followed by the second segment, and then by further segments until all segments used for treatment have been used to deliver the next subset of pulses.
  • a sequence of activation may indicate that segment 1. segment 2, ... , segment N may be activated in this order when each segment receives the subset of pulses. This process may be repeated until all subsets of pulses to be used for treatment have been delivered.
  • combinations of segments may be used to deliver all pulses and/or subsets of pulses.
  • a sequence of activation may indicate that segments 1 and 2, segments 3 and 4, ... , segments N-l and N may be activated in this order when each segment receives the subset of pulses.
  • segments may be overlapped from one activation to another.
  • a sequence of activation may indicate that segments 1 and 2, segments 2 and 3, ... , segments N and 1 may be activated in this order when each segment receives the subset of pulses.
  • Each segment may be activated twice in succession.
  • adjacent segments may be activated in each activation.
  • segments apart from one another by one or more segments may be activated in each activation.
  • selecting a number of segments to be used may be based on lumen diameter.
  • the parameters 114 may include a lumen diameter, a number of segments and/or patterns of segments (adj acent, with intervals, etc.) associated to one another.
  • the computer-readable media 108 may further store executable instructions for monitoring (not shown).
  • the controller 104 may perform the executable instructions for monitoring in order to monitor impedance at the segments and/or a volume of the expandable member and/or a visual indication of catheter diameter with regards to the lumen to determine a number of segments that are likely in contact with, or sufficiently near, tissue to be treated. The number of segments may then be used to deliver treatment energy.
  • the controller 104 may continue or terminate ablation of a portion of or all segments by deactivating the signal generator 1011, and/or changing an activation sequence to skip to the portion or all segments that may not be ablated.
  • Examples of voltages, currents, time durations and/or time constants, electric field strengths, capacitance, and/or a number of pulses may be calculated and/or determined in accordance with methods described herein.
  • parameters such as parameters 114 of FIG. 1 A. may be determined based on measurements taken in the tissue of interest, or a different sample of similar tissue of the same patient or a different patient. For example, measurements may be taken at various voltage levels with particular electrode configurations, and a voltage level, current, pulse pattern, time constant, and other factors may be identified that cause reversible electroporation and the delivery of electrolysis products to result in ablation of the permeabilized cells.
  • Electrolysis products may be generated and may diffuse for a time to cause ablation of the permeabilized cells, but to leave intact the extracellular matrix in the region of the ablated cells.
  • the ablation system 100 may include a power supply 102.
  • the power supply 102 may be coupled to the controller 104 and the generator circuitry 101.
  • the power supply 102 may be implemented using one or more alternating current (AC) power sources, direct current (DC) power sources, batteries, and/or waveform generators.
  • the power supply 102 may supply power to the generator circuitry 101 to generate a voltage and/or current and, therefore, an electric field and/or electrolysis products in the tissue.
  • the flexible circuit 15 may include, for example, segments of electrodes 161, 162, 163, 164.
  • any shape of electrodes may be used, including circular, square, rectangular, or other shapes.
  • the shape of the electrodes may be determined based on a shape of regions to be ablated.
  • the number of segments of electrodes 16 is four; however, the number of segments of electrodes is not limited to four. Any plural number of segments of electrodes 16 may be used to control ablation areas to reduce overstimulation of excitable cells, such as nerves and muscles in tissue.
  • the segments of electrodes 16 may be used to provide ablation, such as both electroporation and electrolysis in some examples.
  • the ablation device 120 coupled to the elongate flexible device 130 may be introduced to a targeted tissue for ablation for delivery of electrolysis products, and regeneration, such as within a cavity or lumen of tissue within an endoluminal zone of a patient.
  • the expandable member 14 may be pressed against the tissue and at least a portion of the segments of electrodes 16 may perform ablation.
  • the segments of electrodes 16 may be disposed within a cavity of the tissue.
  • the segments of electrodes 16 may be on the surface of the tissue, inside the tissue, and/or proximate to the tissue.
  • the elongate flexible device 130 is shown being used to position the segments of electrodes 16 used for permeabilization and/or the generation of electrolysis products, in other embodiments, other ablation devices may be used and/or the segments of electrodes 16 may be positioned proximate to the tissue in other ways — e.g., contacting the tissue with the segments of electrodes 16 may be through probes, a pad including electrodes, needle electrodes, flexible laparoscopic electrodes, or another device coupled to the one or more electrodes to bring the segments of electrodes 16 proximate to the tissue.
  • a combination of parameters in the parameters 114 may be selected to indicate that all pulses to be used for treatment may be provided to a first segment 161, then all pulses provided to a second segment 162, and then to further segments until all segments used for treatment have been used to deliver the treatment energy.
  • a sequence of activation may indicate that segment 161, segment 162, segment 163, and segment 164 may be activated in this order when each segment receives all pulses.
  • segment 161, segment 162, segment 163, and segment 164 may be aligned in an order.
  • a combination of parameters in the parameters 114 may be selected to indicate that a subset of pulses to be used for treatment may be provided to a first segment, then a subset of pulses provided to a second segment, and then to further segments until all segments used for treatment have been used to deliver the subset of pulses. Then the first segment may again be used to deliver another subset of pulses, followed by the second segment, and then to further segments until all segments used for treatment have been used to deliver the next subset of pulses.
  • a sequence of activation may indicate that segment 161, segment 162, segment 163, and segment 164 may be activated in this order when each segment receives the subset of pulses. This process may be repeated until all subsets of pulses to be used for treatment have been delivered.
  • combinations of segments may be used to deliver all pulses and/or subsets of pulses.
  • a sequence of activation may indicate that segment 161 and segment 162 may be activated, then segment 163 and segment 164 may be activated, in this order when each segment receives the subset of pulses.
  • segments may be overlapped from one activation to another.
  • a sequence of activation may indicate that segments 161 and 162, segments 162 and 163, segments 163 and 164, segments 164 and 161 may be activated in this order when each segment receives the subset of pulses.
  • adjacent segments may be activated in each activation.
  • segments apart from one another by one or more segments may be activated in each activation.
  • selecting a number of segments to be used may be based on lumen diameter.
  • the parameters 114 may include a lumen diameter, a number of segments and/or patterns of segments (adj acent, with intervals, etc.) associated to one another.
  • the ablation system 100 may include one or more sensors 18.
  • the one or more sensors 18 may be implemented as part of the elongate flexible device 130, (e.g., a catheter or endoscope), as part of the ablation device 120, and/or as part of a separate instrument.
  • the sensor 18 may be disposed in proximity to the ablation device 120 once the ablation device 120 is introduced to target tissue, such as tissue of the small intestine or other tissues.
  • the controller 104 may determine a number of segments of electrodes 16 that are in contact with, or sufficiently near, tissue to be treated, at least in part, responsive to a sensor signal from the sensor 18.
  • the generator circuitry 101 may energize the selected segments of electrodes 16 in proximity to the treatment region without energizing the unselected segments of electrodes 16.
  • the sensors 18 may include an impedance sensor at the segments.
  • a resistivity meter may be included with the one or more sensors to determine a resistance of the target tissue.
  • a resistivity meter may be provided, for example, on or otherwise coupled to the delivery system.
  • the controller 104 and/or power supply 102 of FIG. 1A may provide an impedance measurement.
  • the impedance measurement may determine a resistivity of the tissue contacted by electrodes 16 of the ablation device 120.
  • the controller 104 and/or power supply 102 may provide a nominal amount of current, such as DC current, through the tissue and receive a resistivity measurement and/or calculate resistivity of the tissue.
  • Electrodes oriented in precise spatial locations may provide improved control over the information gathered through bioimpedance sensing. For instance, if the impedance across each segment was being recorded as an endoluminal device inflated/unfurled to make tissue contact, the impedance would be expected to drop on segments exposed to the tissue. The last segment within which the impedance drops at an individual site may be used as an indicator of the size of the anatomy, such as lumen. Other segments beyond this segment would not be expected to undergo a major impedance shift since these segments would still have no conductive path linking the anode to the cathode. Thus, based on the impedance measurement, the controller 104 may adjust expansion of the expandable member 14 as well as a number of segments to be activated in an activation sequence.
  • the sensors 18 may further include sensors measuring electric field strength, and/or other electrical properties of the tissue 10.
  • the sensors 18 may detect and/or determine electric field strength that may be used. For example, the strength of the electric field at any point may be found by measuring the potential difference between adjacent equipotential lines and dividing by the distance between them. The distance between the lines may be taken along the electric field lines that are perpendicular to the equipotential lines. Gauss meters and/or Tesla meters may be used for this purpose in some examples.
  • an applied voltage, current, capacitance, and/or electric field may be selected, determined, and/or allowed based on a measured resistance of the tissue, the strength of the electric field and/or other electrical properties.
  • a number of pulses of applied voltage may be selected, determined, and/or otherwise used based on a measured resistance of the tissue or other electrical properties.
  • the sensors 18 may detect a volume of the expandable member 14.
  • the sensors 18 may include an imaging device that may provide visual indication of catheter diameter with regards to the lumen.
  • the senor 18 may include a pH sensor.
  • one or more electrodes 16 may function as an anode being acidic (having a pH value less than seven).
  • one or more electrodes 16 may function as a cathode being basic (having a pH value greater than seven).
  • the sensors 18 may include a temperature sensor.
  • the sensors 18 may be coupled to the controller 104, and sensor data, such as impedance, electric field strength, detected volume of the expandable member 14, image data, the pH value, and/or the temperature around the target region of the tissue in proximity to the segments of electrodes 16 may be provided to the controller 104 on the sensor signal.
  • the controller 104 may utilize the sensor data as an indication of tissue ablation and/or potentially damaging pH levels or temperature that may cause, or be close to causing, tissue damage, or an indication of lumen diameter.
  • the controller 104 may combine the sensor data in any manner.
  • the controller 104 may adjust the voltage, current, and/or electric field applied to the tissue responsive to the sensor data of change of segment selections, change of pulsation patterns, etc. For example, if a diameter of lumen is found to be relatively small relative to a total circumference of a wrapped flexible circuit including the segments of electrodes 16, then there may be overlapped segments of electrodes 16 in proximity 7 to a portion of lumen. With one or more overlapping portions of a flexible circuit for a given lumen diameter, the flexible circuit 15 may form multiple layers of electrodes in the overlapped segments of electrodes 16 and a single layer of electrodes with in the non-overlapped segments of electrodes.
  • the controller 104 may reduce the voltage, current, and/or electric field applied to the tissue at the portion of lumen corresponding to the multiple layers of electrodes relative to the nonoverlapped segments by reducing activation of the multi-layer electrodes in proximity of the portion of lumen to balance treatment of the tissue.
  • the use of individually addressable segments of electrodes may allow semiautomated energy delivery without adjusting electrical settings based on size of lumen.
  • electrolytic effects are dependent upon an amount of electrical charge delivered per unit of surface area.
  • the effective electrode surface area depends linearly upon the diameter/radius of the lumen.
  • a self-sizable ablation device with a flexible circuit including wrapped segments of electrodes allows individual segments to be exposed as diameter increases.
  • Such a self-sizable ablation device 120 may allow each segment to contain the same amount of charge and energy without adjustment on the energy output of the generator circuitry' 101. Delivery of energy to more/fewer segments depends upon the number of segments exposed. This ensures that each control volume of tissue receives the same amount of energy.
  • the treatment effect of the ablation device 120 may be irrelevant to size of lumen even if the energy level is fixed at the generator circuitry 101.
  • the controller 104 may use received pH value, temperature and image data to determine a degree of ablation and a location of ablation that may have caused overstimulation of nerves or overexcitement of the cells resulting muscle stimulation. If a pH value at a location is at or beyond a threshold fortissue damage, the controller 104 may reduce a magnitude of electric field or a duration between pulses, or cease application of the electric field. In some examples, if a pH value or a temperature in a region where tissue ablation is desired is at or beyond a threshold for tissue ablation, the controller 104 may cease application of current through electrodes immediately and/or after a desired elapsed electrolysis time to cease the electrolysis process.
  • the controller 104 may control the timing, strength, and duration of electric fields and/or electrolysis products provided by the segments of electrodes 16.
  • the controller 104 may, for example, be programmed to provide an electronic signal to the electrode member 15 through the elongate flexible device 130.
  • the electronic signal may be indicative of a dose of treatment, for example, a dose of electrolysis products.
  • the electronic signal may control the timing and magnitude of a current generated by the one or more electrodes 16 of the electrode member 15 to generate an electric field. This may allow a user to customize treatment of the tissue 10.
  • the controller is coupled to a power supply 102.
  • the power supply 102 may be included in the ablation system 100.
  • the power supply 102 is integrated with the controller 104.
  • a number of pulses may be selected to provide a particular dose (e.g., surface charge) that may control a depth of ablation and/or a ratio of circumferential ablation (e.g., an amount of ablation within a particular circumference may increase). For example, a delivered charge for a number of pulses may be calculated.
  • a particular dose e.g., surface charge
  • a ratio of circumferential ablation e.g., an amount of ablation within a particular circumference may increase.
  • a depth of ablation and/or a ratio of circumferential ablation may be controlled.
  • Devices described herein may control a number of delivered pulses (e.g., voltage pulses) based on a particular depth and/or ratio of circumferential ablation.
  • the amount of circumference of tissue affected by ablation may increase with an increased number of pulses applied.
  • the generation of heat may be reduced and/or avoided by use of the combination of reversible electroporation and electrolysis.
  • the surface charge applied may be a fraction of the surface charge typically used if only electrolysis or only irreversible electroporation were used to achieve ablation.
  • the process of applying the electric field to control ablation, such as causing permeabilization and performing electrolysis may be controlled by computing systems described herein, such as the controller 104 of FIG. 1A in accordance with the executable instructions stored in the computer-readable media 108.
  • An electric field may be applied to at least a portion of the tissue using the electrodes 16.
  • the controller 104 may apply voltages to the electrodes 16 to apply the electric field.
  • fluids or other substances may be injected into, brought into contact with, or otherwise placed in or around the tissue to aid in shaping the electric field generated in the tissue.
  • the electric field may be of a strength in the tissue to cause reversible electroporation in a region of cells targeted for ablation.
  • Electrolysis may be performed to generate products of electrolysis. Electrolysis products may be generated, for example, from ions and molecules of an aqueous solution.
  • the aqueous solution may be the native physiological concentration solution present in the tissue.
  • the ionic composition of bodily fluids may be used as an ionic conductive media te cause the electrochemical reaction forming the basis of electrolysis and/or may be introduced to (e.g., injected into) the tissue during methods described herein.
  • Electrolysis products may be generated by passing a current through tissue using electrodes described herein, such as electrodes 16 of FIG. IB.
  • the electrolysis products may diffuse in the tissue and may ablate permeabilized cells.
  • the time duration during which electrolysis is performed and/or the quantity of electrolysis products is generated may be set herein such that the electrolysis products cause ablation of permeabilized cells, but not ablation of non-permeabilized cells.
  • the time duration and/or quantity of electrolysis products may be set such that the extracellular matrix of the permeabilized cells remains intact, which may facilitate regeneration in the region of the ablated tissue.
  • tissue of an endoluminal organ may be treated where tissue regeneration is desirable or where it is desirable to replace one type of cells with another using the systems.
  • tissue regeneration is desirable or where it is desirable to replace one type of cells with another using the systems.
  • Examples include intestine, duodenum, stomach, bladder, uterus, endometrial lining, endobronchial lining, ovaries, colon, rectum, sinuses, ducts, ureters, prostate, skin, muscle, nerve, diaphragm, kidney, follicles, brain, lymphatic vessels, blood vessels, breast, esophagus, lung, liver, kidney, lymph nodes, lymph node basins, and/or heart.
  • any endoluminal structure may be treated using systems, devices, and techniques described herein.
  • Replacement of one type of tissue with another may be in fibrotic areas where it is desired to replace fibrotic cells with stem cells that can remodulate the area or when pancreatic islets are injected in a part of the liver to generate new sources of insulin.
  • Other tissue may be treated in other examples.
  • FIG. 2A is a schematic diagram of an ablation device 200 according to some examples.
  • the ablation device 200 includes a flexible circuit 220.
  • the ablation device 200 may be the ablation device 120 of FIGS. 1A and IB.
  • the flexible circuit 220 may be the flexible circuit 15 of FIG. IB. While the flexible circuit 220 is illustrated as a planer configuration, the flexible circuit 220 may be in a multiple-layer configuration depending on lumen diameter, as an expandable member, such as the expandable member 14 of FIG. IB, that may expand less to fit relatively small lumen diameters.
  • the flexible circuit 220 may include segments of electrodes 221-224.
  • the segments of electrodes 221-224 may be examples of the segments of electrodes 161-164 of FIG. IB.
  • the segments of electrodes 221-224 may have opposite polarities.
  • the segment of electrodes 221 may include one or more first electrodes 2211 and one or more second electrodes 2212 spaced apart from the one or more first electrodes 2211.
  • the segment of electrodes 222 may include one or more first electrodes 2221 and one or more second electrodes 2222 spaced apart from the one or more first electrodes 2221.
  • the segment of electrodes 223 may include one or more first electrodes 2231 and one or more second electrodes 2232 spaced apart from the one or more first electrodes 2231.
  • the segment of electrodes 224 may include one or more first electrodes 2241 and one or more second electrodes 2242 spaced apart from the one or more first electrodes 2241.
  • the segments of electrodes 221-224 may be coupled to switches 241-244 respectively at ends 216 of the segments of electrodes 221-224.
  • the switches 241-244 may be in the generator circuity 101 of FIG. 1 A.
  • the first electrodes 2211 and the second electrodes 2212 may be coupled to a positive output and a negative output of the switch 241, respectively.
  • the first electrodes 2221 and the second electrodes 2222 may be coupled to a positive output and a negative output of the switch 242. respectively.
  • the first electrodes 2231 and the second electrodes 2232 may be coupled to a positive output and a negative output of the switch 243, respectively.
  • the first electrodes 2241 and the second electrodes 2242 may be coupled to a positive output and a negative output of the switch 244, respectively.
  • the segments of electrodes 221-224 may be configured as segments of independently-addressable or activatable electrodes. In a bipolar configuration, a polarity of voltage to be provided to the first and second electrodes of the respective segments may be switched. Examples of bipolar configuration are described in further detail in regard to FIGS. 9-10B.
  • segments may be activated in a sequence used to deliver all pulses and/or subsets of pulses.
  • FIG. 2B is a schematic diagram of an activation sequence of segments of electrodes 221-224 according to some examples.
  • a sequence of activation may indicate that segment 221.
  • segment 222, segment 223, and segment 224 may be activated in sequence wherein each segment receives 10 pulses, for example.
  • segment 221, segment 222, segment 223, and segment 224 may be arranged in a predetermined order.
  • a sequence of activation may indicate that segment 221 be activated via bipolar actuation, and the switch 241 of FIG. 2A may be activated to provide a number of pulses to segment 221 by providing a positive voltage and a negative voltage to the first electrodes 2211 and the second electrodes 2212, respectively.
  • the sequence of activation may indicate that segment 222 be activated via bipolar actuation, and the switch 242 of FIG. 2A may be activated to provide a number of pulses to segment 222 by providing the positive voltage and the negative voltage to the first electrodes 2221 and the second electrodes 2222, respectively.
  • Electrons may travel from the second electrodes 2222 to the first electrodes 2221. Then the sequence of activation may indicate that segment 223 be activated via bipolar actuation, and the switch 243 of FIG. 2A may be activated to provide a number of pulses to segment 223 by providing the positive voltage and the negative voltage to the first electrodes 2231 and the second electrodes 2232, respectively. Electrons may travel from the second electrodes 2232 to the first electrodes 2231. Then the sequence of activation may indicate that segment 224 be activated via bipolar actuation, and the switch 244 of FIG. 2A may be activated to provide a number of pulses to segment 224 by providing the positive voltage and the negative voltage to the first electrodes 2241 and the second electrodes 2242, respectively.
  • electrons may travel from the second electrodes 2242 to the first electrodes 2241.
  • a polarity of voltage to be provided to the first and second electrodes may be switched.
  • electrons may travel from the first electrodes to the second electrodes in another sequence. Examples of bipolar configuration are described in further detail in regard to FIGS. 9-10B. In this manner, the sequence of activation in the bipolar configuration may be performed using multiple segments of electrodes.
  • anodes may be activated without activating cathodes, and instead, a ground electrode (e.g., the ground pad) may be separately coupled to a patient.
  • a ground electrode e.g., the ground pad
  • pulses of a lower voltage than those of pulses in the bipolar configuration maybe provided.
  • a sequence of activation may indicate that segment 221 be activated via monopolar actuation, then the switch 241 may be activated to provide a number of pulses to segment 221 by providing a positive voltage to the first electrodes 2211. Then the sequence of activation may indicate that segment 222 be activated via monopolar actuation, and the switch 242 may be activated to provide a number of pulses to segment 222 by providing the positive voltage to the first electrodes 2221.
  • sequence of activation may indicate that segment 223 be activated via monopolar actuation, and the switch 243 may be activated to provide a number of pulses to segment 223 by providing the positive voltage to the first electrodes 2231.
  • sequence of activation may indicate that segment 224 be activated via monopolar actuation, and the switch 244 may be activated to provide a number of pulses to segment 224 by providing the positive voltage to the first electrodes 2241.
  • the sequence of activation in the monopolar configuration may be performed using multiple segments of electrodes.
  • the activation sequence of the bipolar configuration may be performed followed by the activation sequence of the monopolar configuration.
  • a shorter, higher-magnitude pulse may be delivered using the bipolar configuration at parameters to cause reversible electroporation of target tissue (e.g., to cause permeabilization of cell membranes in the target tissue).
  • one or more lower- magnitude pulses having a total of relatively long duration may then be delivered using the monopolar configuration at parameters to cause electrolysis and/or electrophoresis (e.g., to cause the products of electrolysis and/or electrophoresis to cause treatment to the permeabilized cells).
  • the one or more pulses may include a gradient which starts with one or more high voltage pulses (e.g., the highest voltage of a sequences), followed by one or more moderate voltage pulses (e.g., lower voltage than the previous set of pulses but higher than a subsequent set), and ending with one or more low voltage pulses (e.g., lower voltage than the previous two sets of pulses).
  • the one or more pulses may include a short high pulse and a long low pulse.
  • the one or more pulses may include a sequence of pulses that have different frequencies.
  • the one or more pulses may include a one or more pulses with a relatively high frequency (e.g., high kHz), one or more pulses with a relatively moderate frequency (e.g., low kHz), and one or more pulses with a relatively low frequency (under 100 Hz).
  • a relatively high frequency e.g., high kHz
  • one or more pulses with a relatively moderate frequency e.g., low kHz
  • one or more pulses with a relatively low frequency under 100 Hz.
  • delivery of energy during the monopolar application of energy may be sufficiently low to avoid the detrimental effects of monopolar energy delivery (e.g., muscle stimulation).
  • bipolar/monopolar techniques could be implemented in conjunction with segments of electrodes. For example, all segments 221-224 may be used to deliver the bipolar, biphasic pulses for electroporation, and then the monopolar pulse(s) may be delivered in a segmented manner as described in FIG. 2B.
  • FIG. 3 shows perspective and cross-section schematic illustrations showing delivery 7 of energy by an ablation device 300, according to some examples.
  • the ablation device 300 may be the ablation device 120 of FIGS. 1A and IB and/or the ablation device 200 of FIG. 2A.
  • the ablation device 300 may include multiple segments of electrodes, such as segments 301, 302 and 303. In a larger lumen, another one or more segments may be utilized.
  • a sequence of activation may indicate that segments 301, 302, 303 may be activated in this order to achieve desired tissue ablation around the circumference of a lumen.
  • the electric field is lower on an inner surface of the ablation device 300 and higher on an outer surface of the ablation device 300.
  • FIG. 4 shows cross-section schematic illustrations of a flexible circuit 400 deployed in various expansion configurations, according to some examples.
  • the flexible circuit 400 may be an example of the flexible circuit 15 of FIG. IB or the flexible circuit 220 of FIGS. 2A and 2B.
  • the flexible circuit 400 may be a spring-wrapped circuit that implements a self-sizing ablation device.
  • the flexible circuit 400 may have an outer portion 408 exposed in proximity 7 to a lumen.
  • the flexible circuit 400 may have an inner portion 410 unexposed to the lumen, wherein the circumference of lumen in contact with the flexible circuit 400 is smaller than the size of the flexible circuit 400.
  • segments of electrodes in the inner portion 410 may not be activated and the segments of electrodes in the outer portion 408 may be activated to provide electrical contact between the outer portion 408 and an endoluminal tissue target.
  • Top views in FIG. 4 show cross-sections of lumens 402, 404, 406 and bottom views show cross-sections of the flexible circuit 400.
  • an expandable member such as the expandable member 14 of FIG. IB may expand less to adjust the size of the outer portion 408 according to the relatively small lumen size, and the size of the inner portion 410 may be about a half of that of the outer portion 408.
  • the expandable member may expand to adjust the size of the outer portion 408 according to a size of the lumen 404, and the size of the inner portion 410 may be about a quarter of that of the outer portion 408.
  • a lumen 406 has a relatively large diameter (e.g., 46 mm in FIG. 4)
  • the expandable member may expand fully to adjust the size of the outer portion 408 according to a size of the lumen 406, and the entire flexible circuit 400 may become the outer portion 408.
  • energy to be delivered to a lumen 402, 404, 406 may pass through the respective outer portions 408 of the flexible circuit 400.
  • FIG. 5A is a flow chart of a method 500 of energy delivery using an ablation device, according to some examples.
  • the method 500 may begin at block 502.
  • segments of electrodes such as segments of electrodes 16, may be positioned about a circumference of target tissue such that a plurality of electrode segments (e.g., a first segment through a final segment) span the circumference.
  • delivery of the electrodes 1 into proximity of tissue in a longitudinal direction may be performed manually using the ablation system 100.
  • a user such as a clinician who uses the ablation device 120, may use direct visualization of the zone by an imaging device such as the sensors 18 during a procedure. The user may manually advance and place the ablation device 120 under direct vision to treat target tissue.
  • some or all of the visualization of a zone of tissue, delivery of the electrodes, proximity of tissue, and treatment of a zone of tissue may be performed under robotically-assisted control.
  • direct visualization of the zone may be utilized by a user to actuate the ablation device 120 using a user input (e.g., operator input system 1106 in FIG. 11) coupled to a servomechanism assembly to move an ablation device 120 under robotic assistance, including the sensor 18, the electrodes 16 and/or the elongate flexible device 130 to the region of ablation to allow for precision to avoid treatment gaps or overlapping zones of ablation.
  • a processor such as the processor 106, or an external computing device coupled to the sensors 18 may autonomously perform visualization of the zone using, for example, image recognition, and may automatically control movement of an elongate flexible device, such as the elongate flexible device 130, and expansion of the expandable member 14 based on the output of the image recognition.
  • image recognition may output an identification of a region of target tissue.
  • the controller 104 or an external computing device may control movement of the elongate flexible device 130 to reach the region of target tissue in the longitudinal direction along an organ.
  • the controller 104 may further control expansion of the expandable member 14 to provide an outward tissue apposition force to the segments of electrodes 16, to ensure sufficient contact between the segments of electrodes 16 and the region of target tissue for ablation.
  • segments of electrodes such as segments of electrodes of a flexible circuit, such as the flexible circuit 400. may be positioned about a circumference of target tissue such that a first segment through a final segment in the outer portion 408 may span the circumference by controlling expansion of the expansion member.
  • visualization and positioning of the elongate flexible device 130 may be based on shape sensing, kinematic data and/or positional data of devices in the elongate flexible device 130 and/or the zone for treatment to precisely place and appose electrodes 16 to perform endoluminal ablation.
  • Robotic systems such as the processor 106 or an external computing device coupled to the controller 104 may use kinematic data and/or positional data in real-time to track treatment zones and treatment progress for enhanced efficacy in real-time.
  • the robotic systems may generate reports for the user regarding a portion of or a total area or volume of tissue (e.g., duodenopathy) treated.
  • the reports may be used to correlate the total area or volume of treatment (e.g., duodenopathy) with dosimetry (e.g.. A1C reduction and/or improved glycemia via continuous glucose monitoring and time-in-range metrics).
  • the processor 106 or the external computing device may provide the computed distance to the user in order to assist the user in some examples to accurately place and reposition the elongate flexible device 130.
  • the user may use the operator input system 1106 to control movement of the robotically actuated elongate flexible device 130 to perform ablation.
  • the processor 106 or the external computing device may further provide information about movement and apposition of the robotically actuated elongate flexible device 130 to inform axial or rotational deployment for optimal circumferential ablation and treatment zones to assist the control by the user.
  • the ablation device 120 may be delivered via a manual or robotic delivery device endoluminally through a trans-oral or trans-anal approach or trans-abdominally with integrated bipolar instrumentation, drop-in probes, or via catheters.
  • the ablation device 120 may be delivered via a manual or robotic delivery device endoluminally through a trans -urethral, trans-perineal. pre-peritoneal, or trans-abdominal approach with integrated bipolar instrumentation, drop-in probes, or via catheters.
  • the ablation device 120 may be delivered via a manual or robotic delivery device endoluminally through a trans-vaginal, trans-perineal, or trans-abdominal approach with integrated bipolar instrumentation, drop-in probes, or via catheters.
  • the ablation device 120 may be delivered via a manual or robotic delivery device endoluminally through a trans-oral approach to reach the ampulla or to go externally into the liver via a trans-gastrointestinal wall route or a trans- abdominal approach with integrated bipolar instrumentation, drop-in probes, or via catheters.
  • the ablation device 120 may be delivered via a manual or robotic delivery device through an endovascular approach or through a keyhole craniotomy with integrated bipolar instrumentation, drop-in probes, or via catheters.
  • the ablation device 120 may be delivered via a manual or robotic delivery' device through an endovascular or a trans-thoracic approach with integrated bipolar instrumentation, drop-in probes, or via catheters.
  • the ablation device 120 may be delivered via a manual or robotic delivery' device endoluminally through a trans-nasal or trans-oral approach with integrated bipolar instrumentation, drop-in probes, or via catheters.
  • the controller may perform treatment of the region of target tissue in a circumferential direction by selectively activating corresponding segments of electrodes 16, without overexciting cells of the tissue treated.
  • energy below a threshold for muscle stimulation is delivered to a portion of the target tissue through a first segment of electrodes (e.g., segment 161) while no energy is delivered to the other segments of electrodes (e.g., segments 162-164).
  • energy below the threshold for muscle stimulation may be delivered to another portion of the target tissue through a second segment of electrodes (e.g., segment 162).
  • the energy delivery' of the method 500 may be controlled by the user through a controller, such as the controller 104. In some examples, the energy delivery of the method 500 may be controlled automatically based on monitoring ablation status by a controller, such as the controller 104. The operations of the method 500 may be executed in an order other than as shown.
  • the ablation may be performed by manually, under robotic assistance, or autonomously moving the ablation device 120 to place electrodes in proximity to the target tissue and apply treatment.
  • FIG. 5B is a flow chart of a method 514 of energy delivery using an ablation device, according to some examples.
  • all pulses are applied segment by segment to segments of electrodes in the ablation device.
  • the method 514 may begin at block 516.
  • all pulses to be used for treatment may be provided to a first segment, such as segment 161, then in operation 520, all pulses may be provided to a second segment, such as segment 162. All pulses may be provided to further segments until all pulses may be provided to a final segment N (where N is a number representing a total number of segments) in operation 522.
  • a sequence of activation may indicate that segment 161, segment 162, segment 163, and segment 164 may be activated in this order when each segment receives all pulses.
  • segment 161, segment 162, segment 163, and segment 164 may be activated in another order.
  • segment 161, segment 162, segment 163, and segment 164 may be activated in a random order, or in a manner that all pulses may be provided to all segments 161-164 once.
  • FIG. 5C is a flow chart of a method 524 of energy delivery' using an ablation device, according to some examples.
  • a subset of pulses is applied segment by segment to segments of electrodes in the ablation device.
  • the method 524 may begin at block 526.
  • a subset of pulses to be used for treatment may be provided to a first segment, such as segment 161, then in operation 530, a subset of pulses may be provided to a second segment, such as segment 162.
  • a subset of pulses may be provided to further segments until all pulses may be provided to a final segment N (where N is a number representing a total number of segments) in operation 532.
  • a sequence of activation may indicate that segment 161, segment 162, segment 163, and segment 164 may be activated in this order when each segment receives a subset of pulses.
  • segment 161, segment 162, segment 163. and segment 164 may be activated in another order; however the order is not limited to this.
  • This subset of energy delivery may be repeated.
  • another subset of pulses to be used for treatment may be provided to the first segment, such as segment 161, in the repeated operation 528. This sequence of delivery of energy by providing subsets of pulses continues until all the pulses are provided to all the segments.
  • FIG. 5D is a flow chart of a method 534 of energy delivery using an ablation device, according to some examples.
  • combinations of segments may be activated simultaneously to deliver all pulses and/or subsets of pulses to the combination of segments.
  • a subset of pulses is applied to multiple segments of segments of electrodes simultaneously in the ablation device.
  • the method 534 may begin at block 536.
  • a subset of pulses to be used for treatment may be provided to multiple segments, such as segments 161 and 162, then in operation 540, a subset of pulses may be provided to multiple segments, such as segments 162 and 163.
  • a subset of pulses may be provided to further segments until all pulses may be provided to a final segment N (where N is a number representing a total number of segments) and segment 1 in operation 542.
  • N is a number representing a total number of segments
  • adjacent segments are activated and each segment may be applied twice in succession.
  • different combination of segments spaced apart may be activated and each segment may be applied twice with an interval.
  • this subset of energy delivery may be repeated until all the pulses are provided to all the segments.
  • FIG. 5E is a flow chart of a method 544 of energy delivery using an ablation device, according to some examples, using a combined bipolar/monopolar technique.
  • the bipolar/monopolar technique may be implemented in conjunction with segmented electrodes. For example, all segments may be used to deliver the bipolar, biphasic pulses for electroporation, and then the monopolar pulse(s) may be delivered in a segmented manner.
  • the method 544 may begin at block 546.
  • the method 544 includes multiple sequences 548 and 550.
  • a bipolar, biphasic configuration may be used and shorter, higher-magnitude pulses of opposite polarities (e.g., positive and negative) may be delivered to segments of electrodes in the ablation device sequentially to cause electroporation of target tissue.
  • the sequence 548 may include operations 552 and 554.
  • a high voltage pulse of a first polarity (positive or negative) to be used for treatment may be provided to all segments 1-N at once.
  • a high voltage pulse of a second polarity' (negative or positive) opposite to the first polarity to be used for treatment may be provided to all segments 1-N at once. Then the sequence 548 may end, and electroporation of the target tissue may be complete.
  • the high voltage pulses may be provided to sequentially to individual segments or pluralities of segments at once, rather than provided to all segments at once.
  • the sequence 550 may be performed.
  • a longer, lower-magnitude pulse may then be delivered segment by segment to segments of electrodes using a monopolar configuration to cause electrolysis and/or electrophoresis.
  • the sequence 550 may include operations 556, 558, and 560.
  • operation 556 low voltage pulses to be used for treatment may be provided to segment 1. then in operation 558, low voltage pulses may be provided to segment 2.
  • Low voltage pulses may be provided to further segments until low voltage pulses may be provided to segment N (where N is a number representing a total number of segments) in operation 560. In this manner, delivery of energy using the monopolar application of energy may be performed. Because energy delivered during the monopolar application of energy may be sufficiently low, the detrimental effects of monopolar energy delivery (e.g., muscle stimulation) may be avoided.
  • monopolar energy delivery e.g., muscle stimulation
  • Muscle stimulation data are shown in FIGS. 6A-6B and FIG. 7 shows data of muscle stimulation.
  • the data may strongly support a relationship between muscle stimulation and an amount of current delivered through an ablation device at a given time.
  • FIG. 3 showing spatial electric field distribution, the data may indicate that lack of current in all directions at a single time may reduce muscle stimulation.
  • FIG. 6A illustrates schematic graphs 602, 604, 606 showing relationships between numbers of pulses and acceleration magnitudes in examples of ablation systems without segmented electrodes.
  • fully circumferential ablation was performed using non-segmented electrodes. Acceleration magnitude was recorded at the ventral surface of a porcine model during in vivo pulse delivery with fully circumferential electrodes under three conditions of voltages and capacitances.
  • 10 pulses were applied, corresponding to 10 peaks in each graph.
  • a horizontal axis represents time (ms) and a vertical axis represents acceleration magnitude (xG).
  • the voltages (and thus current) to provide energy may affect the acceleration magnitudes indicative of muscle stimulation.
  • FIG. 6B illustrates schematic graphs 608, 610, 612 showing relationships between a numbers of pulses and acceleration magnitudes in examples of ablation systems using segmented electrodes.
  • segmented circumferential ablation was performed using axially-oriented segmented electrodes. Acceleration magnitude was recorded at the ventral surface of a porcine model during in vivo pulse delivery' with segments of electrodes under three conditions of voltages and capacitances.
  • FIG. 6B three sets of 10 pulses were applied, corresponding to 10 peaks in each graph.
  • a horizontal axis represents time (ms) and a vertical axis represents acceleration magnitude (xG).
  • FIG. 7 is a table 702 showing relationships between treatment sites, experimental conditions, and results in examples of systems described herein.
  • Experimental conditions include configuration of fully circumferential ("Full") or segmented (“Segment”) electrodes, and electrical energy data including voltage (V), capacitance (pF), peak current (A), impedance (Ohm), and time constant (ms).
  • Observed peak data include acceleration magnitude (xG). Data shown are the mean and standard deviation from 10 or more individual pulses under the experimental conditions in the table 702.
  • the peak current of the fully circumferential electrodes was approximately 22.3 A whereas the peak current of the segmented electrodes was about 10A.
  • the impedance of the fully circumferential electrodes was approximately 19.40hms whereas the impedance of the segmented electrodes was about 46.50hms. Thus much higher impedance was observed for the segmented electrodes.
  • the resulting acceleration magnitude from the fully circumferential electrodes was nearly 4.4xG, whereas the resulting acceleration magnitude from the segmented electrodes was suppressed at approximately 1.3xG.
  • delivery' of energy' using segmented electrodes may likely reduce muscle stimulation.
  • FIG. 8A is a cross-sectional image 802 of an ablation site of a small intestine of a pig after ablation using a conventional ablation system.
  • the conventional ablation system may use fully circumferential electrodes. Several areas of deeper and uneven mucosal damage generated inside tissue can be observed in the image 802.
  • FIG. 8B is a cross-sectional image 804 of an ablation site of a small intestine of a pig after ablation using an example ablation system described herein.
  • the example ablation system may use segmented electrodes. Compared to the image 802, fewer areas of deep damage are observed inside the tissue, and more even ablation can be observed in the inner surface of the tissue. Thus, the ablation using segmented electrodes may be more controlled than the ablation using fully circumferential electrodes.
  • FIG. 9 is a schematic diagram of an example of generator circuitry 900 according to some examples.
  • the generator circuitry 900 may include a signal generator 902 and a switch circuit 904.
  • the switch circuit 904 may be an example of the switches 1013 of FIG. 1, to be coupled to segments of electrodes, segments 1-4 in this example.
  • the switch circuit 904 may include an H-bridge circuit 906 to control multiple signals.
  • the H-bridge circuit 906 may include switches 908, 910, 912, 914.
  • the switch circuit 904 may further include switches 916 and 918 coupled to respective electrodes of segment 1, switches 920 and 922 coupled to respective electrodes of segment 2, switches 924 and 926 coupled to respective electrodes of segment 3, and switches 928 and 930 coupled to respective electrodes of segment 4.
  • the switches 916, 918, 920, 922, 924, 926, 928, 930 may be double pole single throw (DPST) relays.
  • DPST double pole single throw
  • switch 908 When the switch 908 is turned on (e.g., closed), a positive voltage may be provided to switches 916, 920, 924 and 928.
  • switch 912 When the switch 912 is turned on (e.g., closed), a negative voltage may be provided to switches 916, 920, 924 and 928.
  • switch 910 When the switch 910 is turned on, a positive voltage may be provided to switches 918, 922, 926 and 930.
  • the switch 914 When the switch 914 is turned on, a negative voltage may be provided to switches 918, 922, 926 and 930. Consequently, by controlling the switches 908, 910, 912, 914, polarities of voltages for electrodes in each segment may be controlled and thus a bipolar configuration may be provided to the activated segments.
  • the switches 916, 918, 920, 922, 924, 926, 928, 930 may be controlled, for example, by the controller 104, where the processor 106 may be performing the executable instructions for selecting segments 112.
  • the controller 104 may allow- a user to specify an order to deliver pulses to different segments by selecting a sequence of pulses being output by the generator circuitry 900 described herein.
  • FIG. 10A is a schematic diagram of electrodes 1004 including cathodes and anodes according to examples described herein.
  • An exponential decay pulse 1002 may be generated using a bipolar configuration.
  • the exponential decay pulse 1002 may combine a short high electric field pulse for electroporation and a long low electric field for electrolysis.
  • substantial gas may be generated at cathodes. Such gas may impede current flow and may result in risk of arcing when subsequent high amplitudes of pulses are delivered.
  • FIG. 10B is a schematic diagram of electrodes 1008 functioning as anodes and cathodes according to examples described herein.
  • Short high voltage bipolar square pulses 1006 may be applied to each electrode, and cells in target tissue may be electroporated (e.g., via reversible or irreversible electroporation in some examples) with negligible electrical charge.
  • These bipolar pulses alternating anode and cathode functions of each electrode may reduce changes in pH value and cause fewer bubbles around the target tissue, and thus less likely to cause muscle stimulation during electroporation.
  • FIG. 10C is a schematic diagram of electrodes 1012 functioning as anodes and cathodes according to examples described herein.
  • Long low voltage monopolar square pulses 1010 may be provided to each electrode, and electrochemical effects are provided with negligible number of bubbles.
  • a distant cathodic ground pad having a much larger surface area than electrodes in an ablation device may be included in a system to reduce charge density at the ground level. By including the ground pad, bubbles and pH level changes around the target tissue may be reduced, and thus less likely to cause muscle stimulation during electroporation.
  • waveforms may be used to deliver electrolytic electroporation.
  • the waveforms described herein may be used with segmented electrodes as described herein and/or may be used with other electrode designs.
  • An exponential decay waveform may be generated using a capacitive discharge.
  • systems described herein may utilize a capacitance that may be presented by a generator (e.g., C g en).
  • the generator may include one or more capacitors and/or variable capacitors such that a capacitance may be selected by a user.
  • System described herein may be applied to a resistive load (e.g.. Rioad).
  • the resistive load may include, for example, resistance of tissue to be treated, electrodes, one or more resistive elements (e.g.. resistors) and/or other system components.
  • a voltage or current pulse may be used to charge the capacitor, C gen , and the charged capacitor may discharge through the resistive load In this manner, C gen may be discharged through Rioad,
  • the discharge of the capacitance through the resistance may provide an exponentially decaying voltage and/or current waveform.
  • a single pulse may be provided or multiple pulses may be provided spaced by an inter-pulse interval time (e.g., time T).
  • Each pulse may include a voltage at an initial magnitude which then exponentially decays in accordance with the capacitive discharge.
  • the initial voltage magnitude may be given as Vo and the rate of decay i which may be given by Rioad*C g en.
  • the pulse shape (e.g., rate of decay) may be dependent on a resistive load
  • the overall charge delivered to tissue may be preserved across different loads.
  • an overall amount of charge delivered to tissue may be similar between different resistive loads in some examples, although the rate of decay may be different.
  • electroporation may be primarily caused by an initial voltage application, however the voltage application may continue to cause electroporation during some length of time as the waveform decays.
  • a high voltage application may tend to cause muscle contractions in the patient being treated. Accordingly, use of an exponentially-delaying waveform alone may be disadvantageous in some examples, because electroporation may occur for longer than useful, corona discharge risk may be present and/or muscle contractions may occur.
  • increasing a voltage of a pulse or a length of a pulse may typically provide a linear increase in charge delivered to tissue.
  • the overall charge delivered is related to the extent of electrolysis applied.
  • Increasing the peak voltage may yield an exponential increase in energy, which may increase the risks of unwanted hearing and/or of arcing.
  • an increase in pulse length may increase charge per pulse in a lower risk manner than increasing the charge per pulse by increasing the current and/or voltage amplitude. It may generally be advantageous to deliver electrolysis using lower voltage pulses to mitigate these types of risk.
  • increasing pulse length may provide a linear increase in charge delivery 7 and a linear increase in energy.
  • increasing current and/or voltage amplitude may provide a similar linear increase in charge with a generally riskier exponential increase in energy delivered.
  • FIG. 11 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 11 is an example of a chopped capacitive discharge pulse.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1A, including generator circuitry 101.
  • the waveform of FIG. 11 includes a capacitive discharge pulse which may be interrupted, or stopped, periodically to break up the energy delivered and/or reduce the duty cycle of the applied pulses.
  • the generator circuitry 101 may include one or more switches to open and/or close a circuit used to discharge one or more capacitors, providing the breaks in the waveform seen in FIG. 11.
  • the pulse shown in FIG. 11 includes multiple sub-pulses, each of which have a magnitude equal to a respective portion of an exponential decay waveform.
  • the voltage may be zero, or another low value, between the sub-pulses.
  • reduction of the time between sub-pulses may aid in mitigating corona discharge by promoting production of smaller gas bubbles, providing more time for bubbles to diffuse from the electrodes, and/or reducing a peak temperature around the electrodes which may mitigate bubble formation. Shortening the ‘on’ portions and providing delay between the sub-pulses may help mitigate muscle stimulation and promote reduction of corona discharge and/or arcing.
  • FIG. 12 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 12 is an example of a biphasic chopped exponential (e.g., capacitive) discharge pulse.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1A, including generator circuitry 101.
  • the pulse shown in FIG. 12 includes multiple sub-pulses, each of which have a magnitude equal to a respective portion of an exponential decay waveform.
  • the voltage may be zero, or another low value, between the sub-pulses.
  • Each consecutive sub-pulse alternates its polarity.
  • a first sub-pulse has a positive magnitude
  • a next sub-pulse has a negative magnitude.
  • the polarity of each sub-pulse is alternated after each delay between sub-pulses.
  • the delay may range between microseconds to milliseconds in various examples. In some examples, a delay on an order of microseconds may be used between subpulses of opposite polarity, and a delay on an order of milliseconds may be used between subpulses of same polarity.
  • Biphasic pulsing may reduce muscle stimulation and/or contractions. Biphasic pulsing may facilitate a spread of electrolysis products more equally between the electrodes, which may reduce cathodic gas build up and therefore corona discharge tendency.
  • the biphasic chopped exponential discharge may be implemented, for example, by including an H-Bridge circuit in the generator circuitry 101. By controlling switches in the H-bridge, the voltage polarity' provided may be alternated.
  • Examples of systems described herein may utilize waveforms for electrolytic electroporation (e.g., electrolysis and electroporation) which may have an initial portion used primarily to control electroporation and a subsequent portion used primarily to control electrolysis.
  • the first portion may generally utilize voltage amplitudes on the order of hundreds of volts.
  • the second portion may generally utilize voltage amplitudes on the order of tens of volts.
  • the first portion may generally occur over a time frame on the order of microseconds.
  • the second portion may generally occur over a time frame on the order of milliseconds. While a first and second portion have been described, the temporal order may vary in various examples.
  • either portion may be implemented as an exponential decay waveform.
  • FIG. 13 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 13 is an example of a waveform utilizing a higher voltage biphasic chopped discharge portion, and a long, low-voltage pulse portion.
  • a long portion herein may be used to refer to a duration of a low-voltage pulse used to deliver electrolysis to a treatment region.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1A, including generator circuitry 101.
  • An initial portion of the waveform shown in FIG. 13 has a voltage magnitude of around 500V, which decays during a time period on the order of microseconds (e.g., between 10-200 microseconds in some examples).
  • This initial portion includes a biphasic chopped portion, with sub-pulses having alternating polarity and a delay between them.
  • a second portion of the waveform shown in FIG. 13 has a constant voltage on the order of tens of volts for a duration on the order of milliseconds.
  • the second portion of the pulse may last 5-200 ms, although other times may be used.
  • the biphasic chopped pulse has been described, for example, with reference to FIG. 12.
  • the addition of a low voltage DC pulse as a second portion of the waveform may introduce additional charge to a treatment area. Accordingly, for a same charge delivery, it may be possible to use a lower initial charge delivery when some charge is delivered using a trailing DC pulse as shown in FIG. 13. This may aid in avoiding muscle stimulation, reducing the risk of corona discharge, and/or mitigating thermal effects.
  • FIG. 14 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 14 is an example of a waveform utilizing a high voltage, low capacitance portion and low 7 voltage, high capacitance portion.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1A, including generator circuitry 7 101.
  • a first portion of the waveform is a pulse having an exponential decay.
  • the second portion of the waveform of FIG. 14 is also a pulse having an exponential decay.
  • the first pulse is shaped generally to cause electroporation.
  • an initial voltage magnitude of the first pulse may be sufficiently high to cause electroporation, e.g., 500V in some examples, although other voltages may be used.
  • a lower capacitance may be used to generate the first pulse than the second pulse, causing the higher voltage first pulse to decay more quickly than the second pulse.
  • the second pulse may be sized to create electrolysis products.
  • the initial magnitude of the second pulse may be 100V or lower in some examples, although other voltages may be used.
  • the decay of this second pulse may be longer (e.g., a higher capacitance may be used). Accordingly, the initial pulse may decay within 5 ms while the second pulse may take 100s of milliseconds to decay.
  • the waveform shown in FIG. 14 may be repeated multiple times to effect treatment.
  • electrolytic electroporation may be achieved using generator circuitry for creating an exponential decay pulse.
  • Switches may be used to connect a first capacitance and voltage source for the first portion of the waveform, and then to connect a second capacitance and voltage source for the second portion.
  • a first capacitor or set of capacitors are charged to the initial voltage for the first portion of the waveform and allowed to discharge, then additional capacitors may be charged to the lower voltage of the second waveform and allowed to discharge.
  • the high voltage in the first portion of the waveform may be delivered very quickly (e.g., using smaller capacitors) to limit charge buildup initially, which may prevent or reduce gas accumulation.
  • the lower voltage of the second portion may be used to deliver electrolysis.
  • the first portion and the second portion of the waveform may be separately tuned.
  • the peak voltage of the first and second portions may be selected separately and/or independently.
  • the capacitance used to discharge the first voltage and the second voltage may be selected separately and/or independently. Delivering a majority of the charge to the treatment area using a low voltage setting may reduce muscle stimulation and/or corona risk.
  • examples of waveforms described herein may have a first portion of a waveform (e.g., a first portion of a pulse) primarily to control electroporation and a second portion of the waveform (e.g., a second portion of a pulse) primarily to control electrolysis.
  • the first and second portions may be continuous.
  • FIG. 15 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 15 is an example of a waveform utilizing a high voltage, low capacitance portion and low voltage, high capacitance portion which are continuous.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1 A, including generator circuitry 101.
  • the waveform of FIG. 15 may have similar operation and benefits as the discontinuous example described with reference to FIG. 14.
  • the low-voltage, higher capacitance portion of the waveform may be delivered as a continuous extension of the high voltage decay.
  • a capacitor or set of capacitors may be charged to the initial voltage and allowed to discharge.
  • additional capacitors are charged to the starting voltage and allowed to discharge. In this manner, a continuous waveform may be used.
  • Examples of systems described herein may utilize waveforms for electrolytic electroporation (e.g., electrolysis and electroporation) which may have an initial portion used primarily to control electroporation and a subsequent portion used primarily to control electrolysis. In some examples, either portion may be implemented using a square wave.
  • electrolytic electroporation e.g., electrolysis and electroporation
  • either portion may be implemented using a square wave.
  • FIG. 16 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 16 is an example of a waveform utilizing a short high voltage portion, and a longer, low-voltage portion.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1A, including generator circuitry 101.
  • both portions are implemented using square waves.
  • One or more high-voltage, relatively short pulses may be used in the first portion to control electroporation.
  • a voltage of several hundred volts may be used (e.g., 500V).
  • the voltage may be 100-1000V in some examples, 200-800V in other examples.
  • Other voltages may be used.
  • the short pulses may be tens or hundreds of microseconds in length.
  • a pulse may be 10-200 microseconds in length.
  • a single short pulse is shown in FIG. 16, but multiple pulses may be used in other examples.
  • the pulse may be shaped as a square wave - with a voltage applied to electrode(s) at the start of the pulse, and disconnected from the electrode(s) at the end of the pulse.
  • Generator circuitry described herein may include one or more switches controlled to connect and disconnect the voltage.
  • the long pulse may have a smaller voltage magnitude as described herein and may be tens or hundreds of milliseconds in length. The smaller voltage magnitude may be less than 100 V in some examples, less than 80 V in some examples, less than 50 V in some examples, around 10V in some examples.
  • the longer pulse may be 5-200 milliseconds in length. A single long pulse is shown in FIG. 16, but multiple may be used in other examples.
  • the pulse may be shaped as a square wave - with a voltage applied to electrode(s) at the start of the pulse, and disconnected from the electrode(s) at the end of the pulse.
  • Generator circuitry described herein may include one or more switches controlled to connect and disconnect the voltage.
  • a single short pulse and a single long pulse are shown in the example of FIG. 1 . However, in some examples, multiple short pulses may be used prior to one or more long pulses. Moreover, the waveform shown in FIG. 16 may be repeated with a time interval T between the repetitions. Accordingly, one or more short pulses may be applied followed by one or more long pulses. The pattern may then be repeated for a duration of treatment.
  • the square waves shown in FIG. 16 may be advantageous because they may be readily controlled by simple generator circuitry.
  • the waveform is not load dependent in the way that a capacitive discharge waveform is load dependent. Tuning a length and magnitude of the short high voltage pulse(s) allows for a balance between electrolysis and electroporation while delivering charge significantly through the longer, shorter voltage pulses may reduce thermal risk and muscle stimulation.
  • Examples of systems described herein may utilize waveforms for electrolytic electroporation (e.g., electrolysis and electroporation) which may have an initial portion used primarily to control electroporation and a subsequent portion used primarily to control electrolysis.
  • the second portion may be implemented using a sine ware or other charge balanced waveform.
  • FIG. 17 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 17 is an example of a waveform utilizing a short, high-voltage portion, and a longer, sine ware low-voltage portion.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1A. including generator circuitry 101.
  • the first portion of the w aveform is implemented using a square wave, while the second portion is implemented using a sine w ave.
  • the first portion may utilize one or more high-voltage, relatively short square wave pulses as generally- described herein, such as with reference to FIG. 16.
  • the first portion may be implemented using a sine wave.
  • the second portion may be implemented using a longer duration sine ware.
  • the longer duration sine w ave may have a smaller voltage magnitude as described herein and may be tens or hundreds of milliseconds in length. For example, a pulse may be 5-200 milliseconds in length.
  • a single long sine wave is shown in FIG. 17, but multiple sine wave pulses may be used in other examples.
  • the pulse may be shaped as a sine wave - with a variable voltage applied to electrode(s).
  • the frequency of the sine wave may be generally in the kHz range. In some examples a frequency on the order of hundreds of Hz may be used.
  • Generator circuitry described herein may include and/or be coupled to one or more alternating current and/or voltage source to provide a sine wave portion of the waveform.
  • a single short pulse and a single sine wave pulse are shown in the example of FIG. 17. However, in some examples, multiple short pulses may be used prior to one or more long sine wave pulses. Moreover, the waveform shown in FIG. 17 may be repeated with a time interval T between the repetitions.
  • the time interval T may be a fixed time interval in some examples. In some examples, the time interval T may be set value to be used in examples where repetitions are synchronized to a cardiac cycle or other event. Accordingly, one or more short pulses may be applied followed by one or more long pulses. The pattern may then be repeated for a duration of treatment.
  • the use of a sine wave in some examples may allow for a simpler design of generator circuitry described herein.
  • the sine wave is generally a charge-balanced waveform when provided with little or no DC offset.
  • the voltage waveform may be positive in magnitude for an equal period of time that the voltage waveform is negative in magnitude.
  • the charge delivered by the sine wave portion of the waveform is balanced. This may facilitate the production of electrolysis products while advantageously avoiding or reducing pH accumulation at one or more electrolysis electrodes.
  • the balanced charge delivery may avoid and/or reduce tissue whitening at a particular electrode which may be due to anodic electrode behavior.
  • the use of a sine wave portion of the waveform may reduce muscle stimulation.
  • Examples of systems described herein may utilize waveforms for electrolytic electroporation (e.g., electrolysis and electroporation) which may have an initial portion used primarily to control electroporation and a subsequent portion used primarily to control electrolysis.
  • the first portion may be implemented using biphasic pulses.
  • FIG. 18 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 18 is an example of a waveform utilizing a short, biphasic high-voltage portion, and a longer low-voltage portion.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1A, including generator circuitry 101.
  • the first portion of the waveform is implemented using biphasic square waves, and the second portion is implemented using a lower-voltage wave.
  • the second portion may utilize one or more low-voltage, relatively long square wave pulses as generally described herein, such as with reference to FIG. 16.
  • the second portion may utilize one or more low-voltage, relatively long sine wave pulses as generally described herein, such as with reference to FIG. 17.
  • the first portion of the example waveform of FIG. 18 may be implemented using a biphasic square wave.
  • the shorter duration biphasic square wave may have a larger voltage magnitude as described herein and may be tens or hundreds of microseconds in length including multiple sub-pulses.
  • Each sub-pulse of the biphasic square wave may generally be between 1 to 10 microseconds in length.
  • a voltage magnitude of several hundred volts may be used (e.g., 500V).
  • the voltage magnitude may be 100-1000V in some examples, 200-800V in other examples. Other voltages may be used.
  • FIG. 18 Five short biphasic pulse pairs and a single lower voltage square wave pulse are shown in the example of FIG. 18. However, in some examples, other numbers of biphasic short pulses may be used prior to one or more longer square or sine wave pulses. Moreover, the waveform shown in FIG. 18 may be repeated with a time interval T between the repetitions. The time interval T may be fixed and/or variable.
  • a biphasic square wave with shorter sub-pulses may even further reduce a risk of muscle stimulation relative to a somewhat longer monophasic high voltage pulse.
  • such small sub-pulses, or ‘‘bursts'’ may reduce a risk of cardiac arrhythmia during treatment.
  • Examples of systems described herein may utilize waveforms for electrolytic electroporation (e.g., electrolysis and electroporation) which may have an initial portion used primarily to control electroporation and a subsequent portion used primarily to control electrolysis.
  • the biphasic pulses used in the first portion may have a DC offset.
  • the use of biphasic pulses with a DC offset may reduce or eliminate a need for two temporal portions of the waveform.
  • a biphasic square wave pulse with a DC offset may be used to both control electrolysis and electroporation.
  • FIG. 19 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 19 is an example of a waveform utilizing a short biphasic high voltage wave with a DC offset.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1A, including generator circuitry 101.
  • the shorter duration biphasic square wave may have a larger voltage magnitude as described herein and may be tens or hundreds of microseconds in length including multiple sub-pulses.
  • Each sub-pulse of the biphasic square wave may generally be between 1 to 10 microseconds in length.
  • Sub-pulses may be used and repeated with a delay between each sub-pulses.
  • the overall application of sub-pulses may be milliseconds in length in some examples.
  • a voltage magnitude from a DC offset of several hundred voltage may be used (e.g., 500V).
  • the voltage magnitude may be 100- 1000V in some examples, 200-800V in other examples. Other voltages may be used.
  • the voltage magnitude alternates between above and below a DC offset in adjacent subpulses.
  • the DC offset may have a value as described herein with reference to a second portion of waveforms used to control electrolysis.
  • a DC offset of 100V or less may be used. 80V or less in some examples. 50V or less in some examples.
  • treatment may include application of a short biphasic high voltage waveform with DC offset.
  • the waveform of FIG. 19 may be followed by an additional low voltage square and/or sine wave for additional delivery of electrolysis.
  • a total length of a low-voltage portion of the pulse (e.g., the DC offset) may be maximized since it is applied even during application of a higher voltage portion.
  • This may allow an even lower voltage to be used as the DC offset (e.g., less than 50V and/or less than 25V in some examples).
  • the lower DC offset may further reduce incidents of muscle stimulation.
  • pre-pulses may be provided prior to a high voltage portion of a pulse.
  • pre-pulses may be used before application of a voltage greater than 100V, greater than 250V in some examples.
  • the pre-pulses may be of increasing magnitude.
  • FIG. 20 is a schematic illustration of a waveform which may be utilized in examples described herein.
  • the waveform shown in FIG. 20 is an example of a pre-pulses which may be used prior to application of a high voltage pulse described herein.
  • the waveform may be delivered to electrodes described herein using systems and/or generators described herein, such as using the system of FIG. 1 A, including generator circuitry 101.
  • pre-pulses are shown applied prior to use of an exponential decay pulse.
  • pre-pulses may be used before any of the pulse shapes described herein. Any number of pre-pulses may be used, such as between 1 to 10 pre-pulses.
  • the prepulses may increase in magnitude, beginning at a voltage lower than 50V, or lower than 100V in some examples.
  • a first pre-pulse may not stimulate muscle and/or nerve tissue.
  • Each subsequent pre-pulse may recruit additional muscle and/or nerve cells, gradually causing a gentle contraction.
  • stimulatory muscle may already be contracted, avoiding a sharper, more violent muscle contraction event. This slower, more controlled muscle contraction may result in a safer treatment, or reduce the extent or effect of muscle stimulation.
  • any combinations of the waveforms shown and described with reference to FIGS. 11 -19 may be used.
  • the waveforms shown in FIGS. 11 -19 may be repeated any number of times, such as 1-20 times.
  • Each waveform may be delivered in a bipolar or monopolar manner.
  • biphasic waveforms may be preferable for delivery of high-voltage pulses to avoid significant muscle stimulation.
  • low-voltage pulses may be used at around 10V or lower to allow for pulse delivery' without muscle contraction.
  • generator circuitry examples are described herein, such as the generator circuitry 101 of FIG. 1.
  • the patient may be isolated from generator circuitry using a transformer. Examples of waveforms which utilize an AC portion may accordingly be provided to the patient through the transformer without a need for an AC-DC converter. Capacitors and/or capacitor networks may be provided in the waveform generator to provide the discharge of high voltage pulses described herein.
  • waveform generators are used which may provide cardiac synchronization.
  • the first portion of the waveform may be delivered synchronized with a cardiac cycle.
  • the waveform generator e.g.. generator circuitry 101
  • the waveform generator may receive a signal indicative of a portion of the cardiac cycle, and the waveform generator may deliver the first portion of the waveform responsive to an indication of the refractory period in the cardiac cycle.
  • the manipulator system can include one or more manipulators that can be operated with the assistance of an electronic controller (e.g., computer) to move and control functions of one or more instruments when coupled to the manipulators.
  • an electronic controller e.g., computer
  • FIG. 21 illustrates an embodiment of a robotically-assisted manipulator system for use with the systems described herein (also referred to as a robotically-assisted servomechanism system).
  • the manipulator system can be used, for example, in surgical, diagnostic, therapeutic, biopsy, or non-medical procedures, and is generally indicated by the reference numeral 2100.
  • a robotically-assisted servomechanism system 2100 can include one or more manipulator assemblies 2102 for operating one or more medical instrument systems 2104 in performing various procedures on a patient P positioned on a table T in a medical environment 2101.
  • the manipulator assembly 2102 can drive catheter or end effector motion, can apply treatment to target tissue, and/or can manipulate control members.
  • the manipulator assembly 2102 may drive one or more catheters as described herein and/or assist with positioning of portions of the ablation system 100 of FIG. 1A.
  • the manipulator assembly 2102 can be teleoperated, non-teleoperated, or a hybrid teleoperated and non-teleoperated assembly with select degrees of freedom of motion that can be motorized and/or teleoperated and select degrees of freedom of motion that can be non-motorized and/or non-teleoperated.
  • An operator input system 2106 which can be inside or outside of the medical environment 2101, generally includes one or more control devices for controlling manipulator assembly 2102.
  • Manipulator assembly 2102 supports medical instrument system 2104 and can optionally include a plurality' of actuators or motors that drive inputs on medical instrument system 2104 in response to commands from a control system 2112.
  • the actuators can optionally include drive systems that when coupled to medical instrument system 2104 can advance medical instrument system 2104 into a naturally or surgically created anatomic orifice.
  • Other drive systems can move the distal end of medical instrument system 2104 in multiple degrees of freedom, which can include three degrees of linear motion (e.g., linear motion along the X, Y. Z Cartesian axes) and three degrees of rotational motion (e.g., rotation about the X, Y, Z Cartesian axes).
  • the manipulator assembly 2102 can support various other systems for irrigation, treatment, or other purposes. Such systems can include fluid systems (including, for example, reservoirs, heating/cooling elements, pumps, and valves), generators, lasers, interrogators, and ablation components.
  • Elongate flexible devices described herein such as the elongate flexible device 130 of FIG. IB may be coupled to a drive unit (e.g., drive unit 2204) which receives actuation forces from a manipulator assembly (e.g., manipulator assembly 2102) in some examples.
  • a drive unit e.g., drive unit 2204
  • manipulator assembly e.g., manipulator assembly 2102
  • Robotically-assisted servomechanism system 2100 also includes a display system 2110 for displaying an image or representation of the surgical site and medical instrument system 2104 generated by an imaging system 2109 which can include an imaging system, such as an endoscopic imaging system.
  • Display system 2110 and operator input system 2106 can be oriented so an operator O can control medical instrument system 2104 and operator input system 2106 with the perception of telepresence.
  • a graphical user interface can be displayable on the display system 2110 and/or a display system of an independent planning workstation.
  • the endoscopic imaging system components of the imaging system 2109 can be integrally or removably coupled to medical instrument system 2104.
  • a separate imaging device such as an endoscope, atached to a separate manipulator assembly can be used with medical instrument system 2104 to image the surgical site.
  • the endoscopic imaging system 2109 can be implemented as hardware, firmware, software, or a combination thereof which interact with or are otherwise executed by one or more computer processors, which can include the processors of the control system 2112.
  • Robotically-assisted servomechanism system 2100 can also include a sensor system 2108.
  • the sensor system 2108 can include a position/location sensor system (e.g., an actuator encoder or an electromagnetic (EM) sensor system) and/or a shape sensor system (e.g., an optical fiber shape sensor) for determining the position, orientation, speed, velocity, pose, and/or shape of the medical instrument system 2104.
  • the sensor system 2108 can also include temperature, pressure, force, or contact sensors or the like.
  • Robotically-assisted servomechanism system 2100 can also include a control system 2112.
  • Control system 2112 includes at least one memory' 2116 and at least one computer processor 2114 for effecting control between medical instrument system 2104, operator input system 2106, sensor system 2108, and display system 2110.
  • Control system 2112 also includes programmed instructions (e.g., a non-transitory machine-readable medium storing the instructions) to implement a procedure using the robotically-assisted servomechanism system 2100 including for navigation, steering, imaging, engagement feature deployment or retraction, applying treatment to target tissue (e.g., via the application of energy), or the like.
  • Control system 2112 can optionally further include a virtual visualization system to provide navigation assistance to operator O when controlling medical instrument system 2104 during an image-guided surgical procedure.
  • Virtual navigation using the virtual visualization system can be based upon reference to an acquired pre-operative or intraoperative dataset of anatomic passageways.
  • the virtual visualization system processes images of the surgical site imaged using imaging technology such as computerized tomography (CT), magnetic resonance imaging (MRI), fluoroscopy, thermography, ultrasound, OCT, thermal imaging, impedance imaging, laser imaging, nanotube X-ray imaging, and/or the like.
  • CT computerized tomography
  • MRI magnetic resonance imaging
  • fluoroscopy thermography
  • ultrasound optical coheral CT
  • OCT thermal imaging
  • impedance imaging laser imaging
  • nanotube X-ray imaging and/or the like.
  • the control system 2112 can use a pre-operative image to locate the target tissue (using vision imaging techniques and/or by receiving user input) and create a pre-operative plan, including an optimal first location for performing treatment.
  • FIG. 22A shows a medical instrument system 2200 according to some embodiments.
  • medical instrument system 2200 can be used in an image-guided medical procedure.
  • medical instrument system 2200 can be used for nontel eoperational exploratory procedures or in procedures involving traditional, manually operated medical instruments, such as endoscopy.
  • medical instrument system 2200 is interchangeable with, or a variation of, medical instrument system 2104 of FIG. 21.
  • the medical instrument system 2200 may include one or more catheters and/or endoscopes as described herein and/or assist with positioning of portions of the ablation system 100 of FIG. 1A.
  • Medical instrument system 2200 includes elongate flexible device 2202, such as a flexible catheter or endoscope (e.g., gastroscope, bronchoscope), coupled to a drive unit 2204.
  • Elongate flexible device 2202 includes a flexible body 2216 having proximal end 2217 and distal end, or tip portion, 2218.
  • flexible body 2216 has an approximately 14-20 mm outer diameter. Other flexible body outer diameters can be larger or smaller.
  • Flexible body 2216 can have an appropriate length to reach certain portions of the anatomy, such as the lungs, sinuses, throat, or the upper or lower gastrointestinal region, when flexible body 2216 is inserted into a patient's oral or nasal cavity 7 .
  • Medical instrument system 2200 optionally includes a tracking system 2230 for determining the position, orientation, speed, velocity, pose, and/or shape of distal end 2218 and/or of one or more segments 2224 along flexible body 2216 using one or more sensors and/or imaging devices.
  • Tracking system 2230 can optionally be implemented as hardware, firmware, software or a combination thereof which interact with or are otherwise executed by one or more computer processors, which can include the processors of control system 2112 in FIG. 21.
  • Tracking system 2230 can optionally track distal end 2218 and/or one or more of the segments 2224 using a shape sensor 2222. In some embodiments, tracking system 2230 can optionally and/or additionally track distal end 2218 using a position sensor system 2220, such as an electromagnetic (EM) sensor system. In some examples, position sensor system 2220 can be configured and positioned to measure six degrees of freedom, e.g., three position coordinates X, Y, Z and three orientation angles indicating pitch, yaw, and roll of a base point, or five degrees of freedom, e.g., three position coordinates X, Y, Z and two orientation angles indicating pitch and yaw of a base point.
  • six degrees of freedom e.g., three position coordinates X, Y, Z and three orientation angles indicating pitch, yaw, and roll of a base point
  • five degrees of freedom e.g., three position coordinates X, Y, Z and two orientation angles indicating pitch and yaw of
  • Flexible body 2216 includes one or more channels 2221 sized and shaped to receive one or more medical instruments 2226 (e.g., an ablation device 120 or an ablation device 200).
  • medical instruments 2226 e.g., an ablation device 120 or an ablation device 200
  • flexible body 2216 includes two channels 2221 for separate medical instruments 2226; however, a different number of channels 2221 can be provided.
  • FIG. 22B is a simplified diagram of flexible body 2216 with medical instrument 2226 extended according to some embodiments.
  • medical instrument 2226 can be used for procedures and aspects of procedures, such as surgery, biopsy, ablation, mapping, imaging, illumination, irrigation, or suction. Medical instrument 2226 can be deployed through channel 2221 of flexible body 2216 and used at a target location within the anatomy.
  • Medical instrument 2226 can include, for example, image capture devices, biopsy instruments, ablation instruments, catheters, laser ablation fibers, and/or other surgical, diagnostic, or therapeutic tools.
  • Medical tools can include end effectors having a single working member such as a scalpel, a blunt blade, a lens, an optical fiber, an electrode, and/or the like.
  • Other end effectors can include, for example, forceps, graspers, balloons, needles, scissors, clip appliers, and/or the like.
  • Other end effectors can further include electrically activated end effectors such as electrosurgical electrodes, transducers, sensors, imaging devices and/or the like.
  • Medical instrument 2226 can be advanced from the opening of channel 2221 to perform the procedure and then retracted back into the channel when the procedure is complete. Medical instrument 2226 can be removed from proximal end 2217 of flexible body 2216 or from another optional instrument port (not shown) along flexible body 2216.
  • the medical instrument 2226 can be used with an image capture device (e g., an endoscopic camera) also within the elongate flexible device 2202. Alternatively, the medical instrument 2226 can itself be the image capture device.
  • Medical instrument 2226 can additionally house cables, linkages, or other actuation controls (not shown) that extend between its proximal and distal ends to controllably bend the distal end of medical instrument 2226.
  • Flexible body 221 can also house cables, linkages, or other steering controls (not shown) that extend between drive unit 2204 and distal end 2218 to controllably bend distal end 2218 as shown, for example, by broken dashed line depictions 2219 of distal end 2218.
  • at least four cables are used to provide independent '‘up-down” steering to control a pitch motion of distal end 2218 and “left-right” steering to control a yaw motion of distal end 2218.
  • drive unit 2204 can include drive inputs that removably couple to and receive power from drive elements, such as actuators, of the teleoperational assembly.
  • medical instrument system 2200 can include gripping features, manual actuators, or other components for manually controlling the motion of medical instrument system 2200.
  • the information from tracking system 2230 can be sent to a navigation system 2232 where it is combined with information from visualization system 2231 and/or the preoperatively obtained models to provide the physician or other operator with real-time position information.
  • da Vinci® Surgical System such as the da Vinci X®, Xi®, or SP® Surgical Systems, all commercialized by Intuitive Surgical, Inc., of Sunnyvale, California.
  • FIG. 23 illustrates an example embodiment of a drive unit 2204 that can be used as part of the manipulator system 2100.
  • the manipulator system 2300 includes a base 2320, a main column 2340, and a main boom 2360 connected to main column 2340.
  • Manipulator system 2300 also includes a plurality of manipulator arms 2310, 2321. 2312, 2313, which are each connected to main boom 2360.
  • the manipulator arms 2310, 2321, 2312, 2313 can be used as the manipulator assemblies 2102.
  • Manipulator arms 2310, 2321, 2312, 2313 each include an instrument mount portion 2322 to which an instrument 2330 can be mounted, which is illustrated as being attached to manipulator arm 2310. While the manipulator system 2300 depicts four manipulator arms, various embodiments can include more or fewer manipulator arms.
  • Instrument mount portion 2322 can include a drive assembly 2323 and a cannula mount 2324, with a transmission mechanism 2334 of the instrument 2330 connecting with the drive assembly 2323, according to an embodiment.
  • Cannula mount 2324 is configured to hold a cannula 2336 through which a shaft 2332 of instrument 2330 can extend to a surgery' site during a surgical procedure.
  • Drive assembly 2323 contains a variety' of drive and other mechanisms that are controlled to respond to input commands at the operator input system 2106 and transmit forces to the transmission mechanism 2334 to actuate the instrument 2330.
  • FIG. 23 shows an instrument 2330 attached to only manipulator arm 2310 for ease of viewing, an instrument can be attached to any and each of manipulator arms 2310. 2321, 2312, 2313.
  • FIG. 24 illustrates an example embodiment of a manipulator system 2400 that can be used as part of the manipulator system 2100.
  • a portion of a manipulator arm 2440 of the manipulator system 2400 is shown with two instruments 2408, 2410 in an installed position.
  • the schematic illustration of FIG. 24 depicts only two instruments for simplicity, but more than two instruments can be mounted in an installed position at the manipulator system 2400 as those having ordinary' skill in the art are familiar.
  • Each instrument 2408, 2410 includes a shaft 2420. 2430 having at a distal end a moveable end effector or an endoscope, camera, or other sensing device, and can or cannot include a wrist mechanism (not shown) to control the movement of the distal end.
  • the distal end portions of the instruments 2408, 2410 are received through a single-port structure 2480 to be introduced into the patient.
  • the port structure includes a cannula and an instrument entry guide inserted into the cannula. Individual instruments are inserted into the entry guide to reach a surgical site.
  • Transmission mechanisms 2485, 2490 are disposed at a proximal end portion of each shaft 2420, 2430 and connect through sterile adaptors 2450, 2460 with drive assemblies 2470, 2475, which contain a variety of internal mechanisms (not shown) that are controlled by a controller (e.g., at a control cart of a surgical system) to respond to input commands at a surgeon side console of a surgical system to transmit forces to the force transmission mechanisms 2485, 2490 to actuate instruments 2408, 2410.
  • a controller e.g., at a control cart of a surgical system
  • the manipulator systems described herein are not limited to the embodiments of FIGS. 21. 22A-B, 23. and 24, and various other teleoperated, computer-assisted servomechanism configurations can be used with the embodiments described herein.
  • the diameter or diameters of an instrument shaft and end effector are generally selected according to the size of the cannula with which the instrument will be used and depending on the surgical procedures being performed.
  • An ablation system including a flexible circuit with segments of electrodes with polarity control described herein may be used for treatment of stem cells, molecules, genetic material, organoids or other desired cells by ablation, including electroporation and electrolysis on tissue for regeneration.

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Abstract

La présente invention concerne, à titre d'exemple, des techniques d'excitation pour une ablation. Dans certains exemples, un dispositif d'ablation auto-dimensionnable peut comprendre un circuit flexible comprenant de multiples segments d'électrodes. Des circuits générateurs peuvent exciter individuellement des électrodes des multiples segments. Le circuit générateur peut utiliser des champs électriques pulsés pour commander l'activation de segments sélectionnés d'électrodes des multiples segments d'électrodes pour commander une quantité d'énergie appliquée à la région de traitement au-dessous d'un seuil d'énergie pour une stimulation musculaire. Dans certains exemples, le circuit générateur peut fournir des impulsions à des segments d'électrodes d'une manière bipolaire ou monopolaire. En sélectionnant des zones d'ablation par activation sélective de segments d'électrodes dans une séquence, et une quantité et des polarités de tensions ou de courants destinés à exciter des électrodes, une stimulation musculaire peut être réduite. Des exemples de formes d'onde destinées à être utilisées dans la distribution d'énergie sont décrits.
PCT/US2025/012956 2024-01-24 2025-01-24 Appareils, systèmes et procédés de commande de distribution d'énergie à un tissu comprenant des exemples de forme d'onde Pending WO2025160398A2 (fr)

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JP5726084B2 (ja) * 2008-11-11 2015-05-27 シファメド・ホールディングス・エルエルシー 薄型電極アセンブリ
WO2013052590A1 (fr) * 2011-10-04 2013-04-11 Vessix Vascular, Inc. Appareil et procédé de traitement d'une resténose sur endoprothèse
US10188449B2 (en) * 2016-05-23 2019-01-29 Covidien Lp System and method for temperature enhanced irreversible electroporation
US20180303543A1 (en) * 2017-04-24 2018-10-25 Medtronic Cryocath Lp Enhanced electroporation of cardiac tissue
EP3846724A4 (fr) * 2018-09-04 2022-05-11 Inter Science GmbH Procédés, systèmes et appareils pour ablation tissulaire utilisant une impulsion de décroissance exponentielle modulée
IL292334A (en) * 2019-10-21 2022-06-01 Endogenex Inc Devices, systems, and methods for pulsed electric field treatment of the duodenum
JP7459252B2 (ja) * 2019-12-03 2024-04-01 セント・ジュード・メディカル，カーディオロジー・ディヴィジョン，インコーポレイテッド 電気穿孔システムおよび方法
WO2023049954A1 (fr) * 2021-10-01 2023-04-06 Microfield Global Pty Ltd Procédé, systèmes, appareils et dispositifs de caractérisation et d'ablation de tissus cardiaques par électroporation réversible et électrolyse
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