Apparatus and method for tissue ablation

Abstract

Systems, devices, and methods described herein relate to catheter devices for therapy delivery. In some embodiments, the catheter device includes a shaft and a needle, the shaft defining a lumen configured to slidably receive the needle such that the needle can be advanced distally beyond the shaft and penetrate into a tissue site. The shaft further includes a first electrode, and the needle includes a second electrode, the first and second electrodes configured to deliver electroporation to the tissue site.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS)

[0001] This application claims priority to and benefit of U.S. Provisional Patent Application No. 63 / 412,201, entitled "APPARATUS, SYSTEMS AND METHODS FOR TISSUE ABLATION," filed September 30, 2022, the disclosure of which is incorporated herein by reference in its entirety. [Background technology]

[0002] A significant proportion of cancer cases occur in the lungs. Lung cancer screening is often performed using a bronchoscope, which provides image-guided access to potentially cancerous lung nodules. Biopsies can be performed through the bronchoscope to evaluate localized tissue for signs of tumors. If cancer is detected, treatment options include drugs or chemotherapy, interventional treatment methods such as radiofrequency (RF) ablation, or radiation therapy. Side effects associated with such treatments are common. In this context, emerging modalities such as pulsed-field ablation, or electroporation in both irreversible and reversible versions, have the potential to be a form of treatment that minimizes unwanted side effects. While thermal treatments such as RF ablation can result in significant collateral damage because the resulting cellular necrosis zone involves other tissues besides the lung and can generate significant inflammation, pulsed-field ablation is non-thermal and can be tissue-selective, potentially resulting in a smoother healing process with minimal inflammation.

[0003]

[0003] Pulsed-field ablation has emerged as a potentially useful ablation modality that has been investigated in several oncology applications and has recently been found to be beneficial in the context of cardiac ablation for the treatment of cardiac arrhythmias. This non-thermal ablation modality is tissue-selective and can minimize collateral damage, while also providing a natural healing process after ablation that preserves the extracellular matrix and overall tissue integrity. While devices and waveforms suitable in the context of cardiac ablation have been devised, new devices and tools are needed that may be more suitable for use in the context of ablation for the treatment of tumors in other types of soft tissue, such as lung or pancreatic tissue. Summary of the Invention

[0004]

[0004] The present disclosure addresses the need for a minimally invasive device for efficient and effective delivery of pulsed field ablation therapy, particularly for ablation of tumors in lungs and other tissues. Pulsed field ablation procedures can be rapid while minimizing collateral tissue damage often seen in heat-based therapies. At the same time, healing after treatment can be relatively rapid with minimal side effects.

[0005]

[0005] The present disclosure describes tools and devices for minimally invasive access and therapy delivery, for example, for ablation of soft tissue, such as lung or pancreatic tissue. The devices of the present disclosure are intraluminal catheter devices introduced via standard minimal access methods and can have a shaft with a lumen for passage of a wire or needle device, the distal portion of which has at least one electrode disposed therealong. In embodiments, the distal portion of the shaft can also have one or more electrodes disposed thereon. In embodiments, the distal shaft electrode can include an expandable or deformable member including, for example, a shape memory alloy such as nitinol.

[0006] The distal electrode on the wire or needle may include at least one bulbous portion near the distal tip of the wire. In embodiments, the bulbous portion may be substantially spherical in geometry. In embodiments, there may be a non-conductive tapered portion of the wire or needle disposed distal to the bulbous portion. In alternative embodiments, the distal electrode may also include a conductive tapered portion distal to the bulbous portion. In embodiments, the taper may narrow to a sharp point, for example, to penetrate into tissue. In embodiments, the tapered portion may include multiple distinct tapers or a sequence of distinct tapers. In embodiments, the length of the wire or needle other than the exposed distal electrode portion may be electrically insulated or include an insulator. In embodiments, the insulation is configured to withstand a voltage of at least about 300 volts across its thickness without breakdown. In embodiments, the insulation is configured to withstand a voltage of at least about 700 volts across its thickness without breakdown. In embodiments, the insulation is configured to withstand a voltage of at least about 300 volts to at least about 700 volts across its thickness without breakdown, including at least about 400 volts, at least about 500 volts, or at least about 600 volts. In embodiments, the wire can be hollow, and an insulated electrical lead can pass through the hollow portion and connect to a distal electrode on the wire. In embodiments, the insulation of the electrical lead is configured to withstand a voltage of at least about 300 volts across its thickness without breakdown.

[0007] In some embodiments, a lumen within the shaft of the catheter device also carries an insulated electrical lead that connects to the distal shaft electrode. In embodiments, the insulation of the electrical lead is configured to withstand a voltage of at least about 300 volts across its thickness without breakdown. In embodiments, the electrical lead can pass through a second lumen within the shaft of the catheter device. In embodiments, the distal shaft electrode in the form of a deformable member can include a structure in the form of a basket or cage-like structure, which has a diameter in its relaxed state that is larger than the diameter of the catheter shaft. Upon passing through a passage such as a body cavity or bronchial tree, the cage-like structure naturally assumes a compressed shape constrained by the walls of the body cavity such that the distal electrode conforms to the inner diameter of the body cavity or passage, and when the cage-like structure is not mechanically constrained, the distal electrode maintains the relaxed diameter (e.g., expanded diameter) of the cage-like structure.

[0008] In use, in embodiments, the catheter may pass through a lumen or working channel of an endoscopic device, such as a bronchoscope or endoscope, where it may be deflected or steered and navigated to a desired portion of the anatomical structure in a passageway (e.g., the bronchial tree or gastrointestinal tract) under image guidance, for example, via an endoscopic instrument. An imaging device or instrument, such as an optical or ultrasound imaging device implemented via a suitable probe passed through the imaging lumen of the endoscopic instrument, may be used to visualize and guide the placement of the distal end of the catheter as the distal portion of the catheter extends from the endoscopic instrument and is positioned or positioned at or near an area of ​​interest, such as a nodule or tumor site. In embodiments, the catheter device and imaging or endoscopic instrument of the present disclosure may be separately navigated devices that pass side-by through an anatomical passageway.

[0009] Once the catheter is properly positioned within the anatomical structure of interest, a wire or needle is extended from the catheter device and inserted, optionally with image guidance, into the tissue mass desired to be ablated, such as a nodule or tumor site. Following proper insertion of the wire, electroporation ablation is delivered in the form of a series of high-voltage pulses delivered in an appropriate waveform, as described, for example, in International Patent Application No. PCT / US2023 / 025064, entitled "Apparatus, Systems and Methods for Soft Tissue Ablation," filed June 12, 2022, the disclosure of which is incorporated herein by reference in its entirety. In embodiments, the distal electrode on the wire and the distal shaft electrode(s) of the catheter may have opposite electrical polarities for voltage delivery of the ablation waveform. In an alternative embodiment, an electrical reference patch on the surface of the patient, placed in skin contact with the patient, may serve as an oppositely polarized electrode for electrically pairing with the distal electrode on the wire for voltage delivery of the ablation waveform. The electric field generated within the tissue volume around the distal region of the wire upon delivery of the voltage waveform drives tissue ablation. In embodiments, the electric field within this tissue volume is large enough to irreversibly electroporate, i.e., kill, the tissue. In other embodiments, the electric field within the tissue volume around the distal portion of the wire can reversibly electroporate the tissue, causing cells within the tissue to become permeable to the agent over a period of time. In such embodiments, the wire or needle can be hollowed out to inject or deliver a tumor treatment drug or agent directly into the reversibly ablated zone or volume of tissue concomitantly with or immediately after delivery of the electroporation ablation. In this case, systemic or other side effects of the tumor treatment drug or agent can be avoided, since only tissue within the desired zone is permeable to the agent.

[0010]

[0010] Electroporation or pulsed field ablation applications can be repeated at a given site as needed to improve ablation efficacy before moving the catheter to a different location within the intended overall tissue volume and delivering ablation at the different location. Generally, multiple such sites can be targeted in a tumor or tissue mass, e.g., 1 to about 15 such locations can be targeted in each tumor mass, including all values ​​and subranges therebetween.

[0011] The voltage amplitude of the waveform can range from about 300 volts to about 10,000 volts, including all values ​​and subranges therebetween. In embodiments, the diameter of the catheter device can range from about 1 mm to about 6 mm, including all values ​​and subranges therebetween. In embodiments with a distal shaft electrode, the longest diameter of the distal shaft electrode in the relaxed state can range from about 1 mm to about 15 mm, including all values ​​and subranges therebetween. In embodiments, the wire can extend up to about 60 mm beyond the distal tip of the catheter shaft when fully deployed or extended.

[0012] In embodiments, the outer diameter of the main proximal portion of the wire or needle (i.e., the portion proximal to the bulbous portion in the distal region) may range from about 0.2 mm to about 3 mm, including all values ​​and subranges therebetween. In embodiments, the bulbous portion of the distal electrode of the wire may have a maximum diameter of about 0.4 mm to about 4 mm, including all values ​​and subranges therebetween. In embodiments, the length of the distal tapered portion of the wire distal to the bulbous portion of the electrode may range from about 1 mm to about 30 mm, including all values ​​and subranges therebetween. Any section of the length of the distal tapered portion of the wire may be electrically conductive as desired for the embodiment and / or as required for a particular application.

[0013]

[0013] The electrodes of the catheter device, including wires or needles, can be made of, for example, stainless steel, nitinol, gold, platinum-iridium alloy, or other such biocompatible materials known in the art that are suitable for delivering electrical current or voltage to tissue. The catheter shaft can comprise any of a wide variety of polymeric materials known to those skilled in the art, such as, for example, polyurethane, PEBAX, polyethylene, etc. In embodiments, the main proximal portion of the wire can be covered with an electrically insulating material, such as, for example, Teflon, Parylene, Kevlar, etc.

[0014] In embodiments, the distal shaft electrode can comprise a cage-like structure with struts made at least in part from a highly elastic yet flexible material, such as nitinol. The electrode is mounted on the catheter shaft and, in embodiments, can be firmly crimped to the shaft at one end, while the other end fits onto the catheter shaft but is free to move or slide along the shaft as the cage-like structure deforms. In embodiments, the fixed end of the electrode has a collar portion that facilitates crimping or other forms of secure attachment.

[0015]

[0015] In some embodiments, the device comprises an outer shaft defining a lumen, a first electrode disposed at a distal end of the outer shaft, the first electrode including a compressible basket, an inner shaft slidably positionable within the lumen, the inner shaft including a distal tip having a bulbous portion and a tapered portion tapering toward a distal sharp end, the distal tip extending distally relative to the outer shaft and configured for insertion into a tissue site, the distal tip including a second electrode, the first and second electrodes configured to deliver electroporation to a zone of tissue at the tissue site.

[0016]

[0016] In some embodiments, the device includes an outer shaft defining a lumen, a ring electrode disposed at a distal end of the outer shaft, an inner shaft slidably positionable within the lumen, the inner shaft having a distal tip having a spherical portion and a tapered portion tapering toward a distal sharp end, the distal tip extending distally relative to the outer shaft and configured for insertion into a tissue site, the inner shaft including an exposed conductive portion, the ring electrode and exposed conductive portion configured to deliver electroporation to a zone of tissue at the tissue site.

[0017]

[0017] In some embodiments, the system comprises a catheter device including a shaft and a needle, the shaft defining a lumen configured to slidably receive the needle such that the needle can be advanced distally beyond the shaft and penetrate into the tissue site, the shaft including a distally located first electrode having a compressible basket, and the needle including a distally located second electrode; and a pulse generator configured to be coupled to the catheter device, the pulse generator configured to generate and deliver voltage pulses to the catheter device such that the first and second electrodes are polarized with opposite polarities to deliver electroporation to a zone of tissue at the tissue site.

[0018]

[0018] In some embodiments, the method includes positioning a catheter device near a tissue site, the catheter device including a shaft and a needle slidably disposed therein, the shaft including a first electrode located distally with a compressible basket; extending the needle distally from the shaft to insert a distal tip of the needle into the tissue site, the distal tip of the needle including a second electrode; and delivering a voltage pulse to the first and second electrodes to electroporate a zone of tissue at the tissue site. [Brief explanation of the drawings]

[0019] [Figure 1]

[0019] A schematic diagram of an endoscopic device in a target anatomical structure showing the trachea, lungs and associated bronchial tree. [Figure 2]

[0020] 1 provides a diagram of target anatomical structures, including the bronchial tree network in the lung, with illustrated device access pathways. [Figure 3]

[0021] FIG. 1 is a schematic diagram of an endoscopic device engaging a portion of a bronchial tree, showing separate device channels for an imaging device and for other working devices, according to an embodiment. [Figure 4A]

[0022] 1 shows a catheter device of the present disclosure, according to an embodiment, including a wire having a distal shaft electrode in the form of a deformable member and passing through a lumen within the catheter, the wire having a spherical electrode and a tapered portion at its distal end. [Figure 4B]

[0023] 10 illustrates a distal shaft electrode in the form of a deformable member having a cage-like structure with a collar portion at the proximal end of the electrode, according to an embodiment. [Figure 5]

[0024] FIG. 1 is a schematic illustration of a catheter device of the present disclosure passing through a working channel of an endoscopic instrument, according to an embodiment, where the distal end of the catheter is inside the working channel and the distal shaft electrode of the catheter deforms or collapses as it is constrained by the lumen diameter of the working channel. [Figure 6]

[0025] FIG. 1 is a schematic diagram of a catheter device of the present disclosure, according to an embodiment, the distal portion of which emerges from the distal end of the working channel of an endoscopic instrument, showing the spherical electrode at the distal end of the wire and the distal taper such that the distal shaft electrode of the catheter assumes its relaxed or undeformed configuration and an expanded configuration, the wire emerging from the distal end of the catheter. [Figure 7]

[0026] 1 illustrates, according to an embodiment, a catheter device of the present disclosure having a distal shaft in the form of a deformable member and including a wire passing through a lumen within the catheter, the wire having a spherical electrode at its distal end and a tapered portion, the tapered portion of the wire including two sections or portions having separate or different tapers along each section. [Figure 8]

[0027] In accordance with an embodiment, an endoscopic instrument such as a bronchoscope is shown within an anatomical passageway (e.g., a bronchial airway) where a tissue mass or tumor is present at a site along the passageway, and a catheter device of the present disclosure has its distal end inside the working channel of the endoscopic instrument, the endoscopic instrument positioned to allow easy access to the tissue mass using a wire or needle of the catheter device. [Figure 9]

[0028] According to an embodiment, an endoscopic instrument such as a bronchoscope is shown within an anatomical passageway (e.g., a bronchial airway) with a tissue mass or tumor present at a site along the passageway, and a catheter device of the present disclosure has its distal end and distal shaft electrode outside the working channel of the endoscopic instrument, a wire of the catheter device emerging from the distal end of the catheter, and a distal portion of the wire including its spherical electrode that is inserted into the tissue mass or tumor for ablation of the tissue mass. [Figure 10]

[0029] In accordance with an embodiment, an endoscopic instrument such as a bronchoscope is shown within an anatomical passageway (e.g., the bronchial airway or gastrointestinal tract) with a tissue mass or tumor located outside and adjacent the passageway, wherein the catheter device of the present disclosure has its distal end and distal shaft electrode outside the working channel of the endoscopic instrument, the wire of the catheter device emerging from the distal end of the catheter, and the distal portion of the wire including its spherical electrode that is inserted into the tissue mass or tumor for ablation of the tissue mass. [Figure 11]

[0030] 10A-10C are schematic diagrams illustrating an endoscopic instrument, such as an endoscope, within an internal anatomical passageway of a target anatomical structure (e.g., the gastrointestinal tract), according to an embodiment, where a cell mass or tumor is present outside the passageway and in an anatomical organ abutting it, and a wire of the present disclosure emerges from the distal end of the endoscopic instrument, with a distal portion of the wire inserted through the wall of the anatomical passageway into the anatomical organ and tissue mass for ablation of the cell mass. A surface patch or reference patch on the outer surface of the target anatomical structure serves as an electrode that is electrically paired with the distal electrode of the wire having opposite electrical polarity for ablation delivery. [Figure 12]

[0031] 1 illustrates a catheter device including a distal shaft electrode in the form of a ring electrode and a wire passing through a lumen within the catheter or outer shaft, according to an embodiment. [Figure 13]

[0032] 1 illustrates a schematic diagram of a catheter device according to an embodiment. [Figure 14]

[0033] 1 is a flowchart illustrating a method for delivering a treatment using a catheter device as described herein, according to an embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0020]

[0034] Device embodiments of the present disclosure provide for the construction and configuration of a device for delivering electroporation or pulsed field ablation therapy for the ablation of soft tissue tumors. In embodiments, the device is intended for minimally invasive use and, in embodiments, may be used through the working channel of an endoscopic instrument. In alternative embodiments of the method of use, the device may be independently positioned and positioned, and in some such embodiments, the device may be deflectable to allow for easier navigation.

[0021]

[0035] In the context of a pulmonary application, Figure 1 illustrates endoscopic access to the lungs via a bronchoscope 103 introduced into the trachea 109 of a subject 101 and advanced into the airways 107 of the lungs 105. The branching network of the bronchial tree can be accessed at different sublevels of the network. Figure 2 shows in more detail the bronchoscope 203 passing through the bronchial network 201 such that the tip 207 of the bronchoscope 203 is positioned for access to smaller branches of the bronchial network 201. In some cases, pre-operative computed tomography (CT) images can be used as references to guide the bronchoscope 203 to a location of interest, such as the location of a lung nodule or tumor.

[0022]

[0036] 3 illustrates a distal portion of an endoscopic instrument 303 inserted into a body cavity or anatomical passageway 301, such as the bronchial tree or digestive tract, according to an embodiment, showing imaging channels 309 and 311 and a working channel 315 within endoscopic instrument 303. In this example, imaging channel 309 is used to insert a light source for optical imaging, while a camera device can be inserted through imaging channel 311 to visualize the illuminated interior of passageway 301. Working channel 315 can be used to insert other devices, such as, for example, a catheter device for diagnostic or therapeutic delivery. In some cases, an ultrasound imaging catheter can be passed through one of imaging channels 309 and 311 of endoscopic instrument 303 to provide ultrasound images of the anatomical passageway for visualization purposes.

[0023]

[0037] 13 schematically illustrates a catheter device 1301 for delivery of a procedure or therapy, according to an embodiment of the present disclosure. The catheter device 1301 may be structurally and / or functionally similar to other catheter devices described herein. The catheter device may have, for example, a shaft 1302 (e.g., an outer shaft or catheter shaft) defining a lumen 1304 for receiving a wire or needle 1303 (e.g., an inner shaft).

[0024]

[0038] In embodiments, the diameter of catheter device 1301 and other catheter devices of the present disclosure may range from about 1 mm to about 6 mm, including all values ​​and subranges therebetween. In embodiments, the catheter device may be passed through a working channel (e.g., working channel 315) of an endoscopic instrument, while in other embodiments, the catheter device may be positioned alongside and external to the endoscopic instrument. In some embodiments, the catheter device may be deflectable using deflection controlled from the catheter handle, as commonly used in interventional devices. For example, the catheter device may be deflectable using one or more pull wires. In embodiments, the catheter device may have a distal shaft electrode, for example, as described herein, while in alternative embodiments, the distal shaft electrode may not be present and the distal wire electrode may be paired with a reference patch positioned externally on the patient surface for ablation delivery electrical pairing.

[0025]

[0039] As shown in FIG. 13 , the catheter device optionally has one or more electrodes 1305 disposed near the distal end of the shaft 1302. The one or more electrodes 1305 may be implemented as expandable or compressible electrodes (e.g., compressible basket electrodes, cage electrodes, mesh electrodes, etc.) or ring electrodes. In embodiments with a distal shaft electrode (e.g., electrode 1305) having an expandable structure, the longest or largest diameter of the distal shaft electrode in its relaxed state may range from about 1 mm to about 15 mm, including all values ​​and subranges therebetween. The expandable structure may be formed at least in part from a highly elastic or superelastic yet flexible material, such as, for example, Nitinol. In some embodiments, there may be a single electrode 1305 that may be configured to pair with one or more electrodes disposed on another portion of the catheter device 1301 (e.g., wire 1303) to deliver pulsed field ablation or electroporation. In some embodiments, there may be multiple electrodes 1305 that may be configured to pair with another electrode and / or one or more electrodes located on another portion of the catheter device 1301 (e.g., wire 1303) to deliver pulsed field ablation or electroporation.

[0026]

[0040] As described above, the wire 1303 can translate or slide within the lumen 1304 of the shaft 1302. The wire 1303 can extend a predetermined distance from the shaft 1302, for example, to penetrate into a tissue site. In embodiments, the wire can extend up to approximately 60 mm beyond the distal tip of the catheter shaft when fully deployed or extended. The wire 1303 can include a main proximal section 1306, a bulbous section 1307, and one or more tapered sections 1315, 1323. In some embodiments, the wire can include a single tapered section 1315 that tapers to a piercing point or a sharp distal end, while in other embodiments, the wire can include two or more tapered sections 1315, 1323, with the most distal tapered section tapering to a piercing point or a sharp distal end. The piercing point can be a sharp end that can be configured to penetrate into a tissue site. In embodiments, the outer diameter D1 of the main proximal portion of the wire or needle (i.e., the portion proximal to the bulbous portion in the distal region) may range from about 0.2 mm to about 3 mm, including all values ​​and subranges therebetween. In embodiments, the bulbous portion of the distal electrode of the wire may have a maximum diameter D2 of about 0.4 mm to about 4 mm, including all values ​​and subranges therebetween. In embodiments, the length (e.g., L1 + L2) of the distal tapered portion(s) of the wire distal to the bulbous portion of the electrode may range from about 1 mm to about 30 mm, including all values ​​and subranges therebetween. In embodiments, the length L1 of the first distal tapered portion 1314 may be less than the length L2 of the second distal tapered portion 1323. In other embodiments, the length L1 of the first distal tapered portion 1315 may be the same as or greater than the length L2 of the second distal tapered portion 1323. Any segment of the length of the distal tapered portion of the wire (e.g., 0 to 1 inclusive) can be conductive as desired for the embodiment and / or the needs of a particular application. In some embodiments, the first tapered portion 1315 can be non-conductive while the second tapered portion 1323 can be conductive. In other embodiments, the first tapered portion 1315 can be conductive while the second tapered portion 1323 can be non-conductive.In other embodiments, both the first tapered portion 1315 and the second tapered portion 1323 may be conductive.

[0027]

[0041] The generator 1350 can be coupled to an electrode or conductive portion of the wire 1303 and to the electrode(s) 1305. The generator 1350 can be configured to deliver a series of high-voltage pulses to the electrode or conductive portion. In some embodiments, the generator 1350 can be configured to deliver energy in a monopolar mode. In a monopolar mode, one or more of the electrodes or conductive portions on the catheter device can be configured to have one electrical polarity, while a reference patch placed on the subject has the opposite electrical polarity. In some embodiments, the generator 1350 can be configured to deliver energy in a bipolar mode. In a bipolar mode, two different electrodes or subsets of electrodes on the catheter device are energized with opposite electrical polarities. In embodiments, the voltage amplitude of the waveforms described herein can range from about 300 V to about 10,000 V, including all values ​​and subranges therebetween, depending on the application.

[0028]

[0042] 4A illustrates a catheter device of the present disclosure according to an embodiment. The catheter has a catheter shaft 400 with an inner lumen 402 through which a wire 422 passes. The catheter has a distal shaft electrode 404 in the form of a cage-like structure that is deformable and has a diameter in its relaxed state that is larger than the diameter of the catheter shaft 400. In embodiments, the distal shaft electrode 404 may include an expandable or deformable member, generally in the form of a cage-like structure comprising a plurality of struts, including, for example, a shape memory alloy or a superelastic material such as Nitinol. The struts of the structure are flexible and can deform under the application of mechanical stress, while the cage-like structure can return (e.g., rapidly return) to its unstressed configuration when the stress is released. At the same time, the electrode material is electrically conductive and biocompatible.

[0029]

[0043] While a single distal shaft electrode 404 is shown in FIG. 4A , in embodiments, the distal portion of the catheter shaft 400 can have one or more electrodes disposed thereon. An insulated lead wire (not shown) passes through the lumen 402 and connects to the distal shaft electrode 404. In embodiments, the insulated lead wire can pass through a separate, second lumen within the catheter shaft 400. In embodiments, the electrical lead wire insulation is configured to withstand a voltage of at least about 300 volts across its thickness without breakdown. When the catheter device is passed through a body cavity or passageway and mechanically constrained, the electrode 404 naturally deforms or collapses to fit the passageway, and when the electrode 404 is not mechanically constrained, the distal electrode 404 maintains the relaxed diameter of its cage-like structure.

[0030]

[0044] The wire or needle 422 has a spherical distal electrode 406 and a distal taper 408 that narrows to a sharp point for insertion into the cell mass. In embodiments, the spherical portion may be substantially spherical in geometry. In embodiments, the distal taper 408, or a portion thereof, may be conductive, thereby forming an extension electrode together with the spherical portion, while in alternative embodiments, the distal taper 408 may be non-conductive. The majority of the length of the wire proximal to the junction 412 with the spherical electrode 406 may be non-conductive or insulated. In embodiments, the wire insulation is configured to withstand a voltage of at least about 300 volts across its thickness without breakdown. In embodiments, the insulation is configured to withstand a voltage of at least about 700 volts across its thickness without breakdown. In embodiments, the insulation may be configured to withstand a voltage of at least about 300 volts to at least about 700 volts across its thickness without breakdown, including at least about 400 volts, at least about 500 volts, or at least about 600 volts. In embodiments, the wire 422 may be hollow, and an insulated electrical lead may pass through the hollow portion and connect to the distal wire electrode 406.

[0031]

[0045] In embodiments, the electrodes 406 of the catheter device, including those disposed on wires or needles, can be made of stainless steel, nitinol, gold, platinum-iridium alloy, or other such biocompatible materials known in the art that are suitable for delivering electrical current or voltage to tissue. The catheter shaft 400 can comprise any of a wide variety of polymeric materials known to those skilled in the art, such as, for example, polyurethane, PEBAX, polyethylene, etc. In embodiments, the main proximal portion of the wire can be covered with or include an electrically insulating material, such as, for example, Teflon, Parylene, Kevlar, etc. In embodiments, the distal shaft electrode 404 can comprise a cage-like structure with struts made at least in part from a highly elastic yet flexible material, such as nitinol. The electrode 404 is mounted on the catheter shaft 400, and in embodiments, can be firmly crimped to the shaft at one end, while the other end fits onto the catheter shaft 400 but is free to move or slide along the shaft 400 as the cage-like structure deforms. In embodiments, the fixed end of the electrode 404 can have a collar portion that facilitates crimping or other forms of secure attachment and can also be used for attachment of an electrical lead. An example of such an electrode is shown in Figure 4B, where a cage-like structure 451 is illustrated with a collar 453 at the proximal end of the electrode 451. The collar portion can be configured to be fixedly attached to the catheter shaft and attached to a lead, for example, to receive electrical current from a generator (e.g., generator 1350).

[0032]

[0046] 5 is a schematic diagram of an endoscopic instrument 500 having an imaging channel 502 and a working channel 505, according to an embodiment. A therapeutic catheter device 507 of the present disclosure is inserted into the working channel 505. An energy delivery wire 510 having a spherical electrode 513 passes through the catheter device 507. The catheter 507 has a distal shaft electrode 519 in the form of a deformable member or structure. Because the distal end of the catheter 507 is entirely inside the working channel of the endoscopic instrument 500, the distal shaft electrode 519 deforms into a collapsed configuration when positioned within and passing through the working channel 505.

[0033]

[0047] FIG. 6 is a schematic illustration of a catheter device 604 of the present disclosure, according to an embodiment, the distal portion of which is shown emerging from the distal end of a working channel 601 of an endoscopic instrument such that a distal shaft electrode 608 of the catheter 604 assumes its relaxed or undeformed configuration and an expanded configuration. The catheter device 604 may be structurally and / or functionally similar to other catheter devices described herein, including, for example, the catheter devices shown in FIGS. 4A and 5. FIG. 6 also shows a wire 606 passing through the catheter 604, the wire 606 having a spherical distal electrode 610 and a distal taper 612 at its distal end, the wire 606 emerging from the distal end of the catheter 604. The wire 606 may be structurally and / or functionally similar to other wires or needles described herein, including, for example, the wires shown in FIGS. 4A and 5. For clarity, the remainder of the endoscopic instrument is not shown in FIG. 6, but may be structurally and / or functionally similar to the endoscopic instrument shown in FIG.

[0034]

[0048] In embodiments, the distal taper of the wires described herein may have a discrete tapered portion. For example, FIG. 7 shows a catheter device 701 of the present disclosure including a wire 703 having a distal shaft electrode in the form of a deformable member 705 and passing through a lumen within the catheter 701, the wire having a spherical electrode 707 and a tapered portion at its distal end. The tapered portion of the wire 703 may include two sections 715 and 723 having discrete or distinct tapers (e.g., tapering at different rates or according to different curvatures) along each respective section. In embodiments, the distal taper or tapered portion may converge to a sharp point, for example, to facilitate insertion into a tissue mass. While two discrete tapered sections 715 and 723 are shown in this illustration for purposes of providing an example, it will be apparent that single or multiple tapered sections may be used at the distal end of the wire as convenient or necessary for the application at hand, without limitation.

[0035]

[0049] In some embodiments, the distal shaft electrode can be in the form of a ring electrode (or multiple ring electrodes). For example, FIG. 12 shows a catheter device 1201 having a distal shaft electrode in the form of a ring electrode 1205 (or multiple ring electrodes). The catheter device 1201 can have a shaft defining a lumen for receiving a wire 1203. The wire 1203 can be configured to translate or slide within the lumen of the shaft. In use, the wire 1203 can extend distally from the catheter device 1201, as shown in FIG. 12. The wire 1203 can be structurally and / or functionally similar to other wires described herein. For example, the wire 1203 can include a spherical electrode 1207 and a tapered portion at its distal end. The tapered portion of the wire 1203 can include two sections 1215 and 1223 having separate or distinct tapers along each respective section. The tapered portion can converge to a sharp point, for example, to facilitate insertion into a tissue mass. In this figure, two separate tapered sections 1215 and 1223 are shown for purposes of providing an example, but it will be apparent that single or multiple tapered sections may be used at the distal end of wire 1203, as convenient or necessary for the application at hand, without limitation.

[0036]

[0050] In use, the catheters and wires of the present disclosure can be used to access an anatomical location for the purpose of delivering ablation therapy. For example, Figure 8 shows an endoscopic instrument 807 (e.g., a bronchoscope) within an anatomical passageway (e.g., a bronchial airway) with a tissue mass or tumor 819 located at a location along the passageway. The figure shows the working channel of the endoscopic instrument carrying a catheter device 811, the distal portion of which is entirely within the working channel of the endoscopic instrument, positioned to allow easy access to the tissue mass with the wire or needle of the catheter device 811.

[0037]

[0051] Once the endoscopic instrument is properly positioned, for example, using image guidance from an imaging instrument or catheter passed through the imaging channel of the endoscopic instrument, the catheter device can be extended to access the treatment site. For example, FIG. 9 shows an endoscopic instrument 902 (e.g., a bronchoscope) within an anatomical passageway 900 (e.g., a bronchial airway) with a tissue mass, nodule, or tumor 924 located at a site along the passageway. The endoscopic instrument 902 may be structurally and / or functionally similar to other endoscopic instruments described herein, including the endoscopic instrument 807. FIG. 9 shows a catheter device 906 of the present disclosure, with its distal end and distal shaft electrode 916 outside the working channel of the endoscopic instrument 902, and a wire 912 of the catheter device 906 emerging from the distal end of the catheter 906, the distal portion of which includes its spherical electrode 920 inserted into the tissue mass or tumor 924 for ablation of the tissue mass. Positioning of the catheter 906 and wire 912 can be performed using image guidance, if needed.

[0038]

[0052] After proper insertion of the wire, electroporation ablation is delivered in the form of a series of high-voltage pulses delivered in an appropriate waveform, for example, as described in International Patent Application No. PCT / US2023 / 025064, incorporated herein by reference above. In embodiments, the distal electrode on the wire and the distal shaft electrode(s) of the catheter may have opposite electrical polarities for voltage delivery of the ablation waveform. In alternative embodiments, an electrical reference patch on the patient's surface, placed in skin contact with the patient, may serve as an oppositely polarized electrode for electrical pairing with the distal electrode on the wire for voltage delivery of the ablation waveform. The electric field generated within the tissue volume around the distal region of the wire upon delivery of the voltage waveform drives tissue ablation within that volume. The voltage amplitude of the ablation waveform driving electroporation may range from about 300 volts to about 10,000 volts, including all values ​​and subranges therebetween.

[0039]

[0053] In embodiments, the electric field within this tissue volume is large enough to irreversibly electroporate the tissue, i.e., kill the tissue. In other embodiments, the electric field within the tissue volume around the distal portion of the wire can reversibly electroporate the tissue, causing cells within the tissue to become permeable to the agent for a duration or time. In some embodiments, the wire or needle can be hollow to inject or deliver a tumor treatment drug or agent directly into the reversibly ablated zone or volume of tissue concomitantly with or immediately after the electroporation ablation is delivered. In this case, systemic or other side effects of the tumor treatment drug or agent can be avoided, since only tissue within the desired zone is permeable to the agent. Additionally or alternatively, the drug or agent can be injected into the reversibly ablated zone by a separate device or needle.

[0040]

[0054] The electroporation or pulsed field ablation application can be repeated at a given site as needed to improve the ablation effect before moving the catheter to a different location within the intended overall tissue volume and delivering the ablation at the new location. Generally, multiple such sites can be targeted in a tumor or tissue mass, for example, 1 to about 15 such locations can be targeted in each tumor mass, including all values ​​and subranges therebetween. A workflow for using the devices described herein may include the following sequence of steps: (i) inserting a catheter device and an imaging device into the working channel and imaging channel, respectively, of an endoscopic instrument; (ii) inserting the endoscopic instrument to a location near or adjacent to the region of interest using image guidance using the imaging device; (iii) extending a distal portion of the catheter so that its distal shaft electrode is outside the endoscopic instrument; (iv) extending a wire or needle from the distal end of the catheter and inserting the distal portion of the wire and the distal electrode of the wire at least partially within the ablation site; and (v) delivering a high-voltage ablation waveform through the distal electrode of the wire to generate tissue electroporation within the tissue volume around the distal region of the wire.

[0041]

[0055] In embodiments, the region of interest for ablation delivery may be outside or adjacent to an anatomical passageway or cavity. For example, FIG. 10 shows an anatomical passageway 1001 (e.g., the gastrointestinal tract), with a tissue mass 1029 adjacent to the passageway 1001 representing the region of interest for ablation delivery. The tissue mass 1029 may be within an organ (e.g., the pancreas). In FIG. 10 , a catheter device 1005 passes through a working channel of an endoscopic instrument 1003, with its distal end and distal shaft electrode 1017 extending from the working channel of the endoscopic instrument 1003. A wire or needle of the catheter device 1005 extends from the distal end of the catheter 1005, with the distal portion of the wire including its spherical electrode 1033 inserted into the tissue mass or tumor 1029 for ablation of the tissue mass.

[0042]

[0056] After proper insertion of the wire, similar to that described with respect to FIG. 9 , electroporation ablation is delivered in the form of a series of high-voltage pulses delivered in an appropriate waveform, for example, as described in International Patent Application No. PCT / US2023 / 025064, previously incorporated by reference. In embodiments, the distal electrode on the wire and the distal shaft electrode(s) of the catheter may have opposite electrical polarities for voltage delivery. In alternative embodiments, an electrical reference patch on the patient's surface, placed in skin contact with the patient, may serve as an oppositely polarized electrode for electrically pairing with the distal electrode on the wire for voltage delivery of the ablation waveform. The electric field generated within the tissue volume around the distal region of the wire within the tissue mass 1029 upon delivery of the voltage waveform drives tissue ablation within that volume. The voltage amplitude of the ablation waveform driving electroporation may range from about 300 volts to about 10,000 volts, including all values ​​and subranges therebetween.

[0043]

[0057] In embodiments, a wire or needle of the present disclosure can be used to deliver a voltage waveform by electrically pairing it with a reference patch electrode positioned externally on the surface of a patient. For example, FIG. 11 schematically illustrates an endoscopic instrument, such as an endoscope 1109, within an anatomical passageway 1107 (e.g., the gastrointestinal tract) within a body 1105 of a target anatomical structure, with a tissue mass or tumor 1121 located outside the passageway 1107 and within an anatomical organ 1145 abutting the passageway 1107. As shown in FIG. 11 , a wire device 1113 of the present disclosure can extend from the endoscopic instrument 1109, with a distal portion 1127 of the wire 1113 including its distal electrode inserted through the wall of the anatomical passageway into the anatomical organ and into the tissue mass for ablation of the tissue mass 1121. A surface patch or reference patch 1139 on the external surface of the target anatomical structure can be configured as an electrode electrically paired with a distal electrode of a wire having opposite electrical polarity for ablation delivery.

[0044]

[0058] FIG. 14 illustrates a method 1400 of using the endoscopic devices and catheter devices described herein (e.g., any of the endoscopic devices described in FIGS. 1-3 and 8-11 and / or the catheter devices shown in FIGS. 4A-13), according to embodiments. At 1402, the catheter device can optionally be positioned within the working channel of the endoscopic device. Alternatively, the catheter device can be positioned outside the endoscope, e.g., alongside or adjacent to the endoscopic device. In some embodiments, the catheter device can be used without the endoscopic device. At 1404, the endoscopic device and / or catheter device can be positioned near a tissue site, e.g., by navigating the endoscopic device and / or catheter device through a body lumen or cavity. The tissue site can include a tissue mass, nodule, or tumor, or other element requiring treatment. In some embodiments, the endoscopic device can carry the catheter device within the working channel of the endoscopic device. In such embodiments, if the catheter device includes expandable electrodes, the expandable electrodes can be held undeployed or constrained within the working channel of the endoscopic device while the endoscopic device is navigated to the tissue site. In some embodiments, the endoscopic device and the catheter device may be separately positioned at the tissue site, hi some embodiments, the endoscopic device may be configured to provide image guidance for positioning the catheter device at the target site.

[0045]

[0059] At 1406, when the catheter device is positioned within the working channel of the endoscopic device, the catheter device can be extended from the working channel. As described above, the catheter device can include a wire. At 1408, the wire of the catheter device can be extended from the distal end of the catheter shaft of the catheter device so that the distal penetrating tip of the wire can be inserted into the tissue site. At 1410, the catheter device can apply electroporation to a tissue zone at the tissue site. For example, a generator (e.g., generator 1350) can be configured to deliver a voltage waveform to the catheter device to activate one or more electrodes of the catheter device to deliver electroporation. In some embodiments, the generator can be configured to generate an electric field in one or more electrodes having sufficient strength to cause irreversible electroporation. In some embodiments, the generator can be configured to cause the electrodes to reversibly electroporate tissue. Optionally, at 1412, a therapeutic agent can be delivered to the tissue zone at the tissue site. In some embodiments, the wire defines a lumen configured to deliver a fluid or other agent to the tissue zone at the tissue site. In some embodiments, one or more separate devices (e.g., another catheter or drug delivery device) may be configured to deliver fluids or other agents to a zone of tissue at the tissue site. In some embodiments, the catheter device may repeat the application of electroporation one or more times at 1414. For example, electroporation may be repeated at a given site as needed to improve the ablation effect.

[0046]

[0060] In some embodiments, the catheter device can be moved to one or more additional sites (1414: YES) and electroporation can be delivered to those sites. For each new site, the catheter device can be retracted into the working channel of the endoscopic device at 1420 and / or the wire can be retracted into the catheter shaft, and the endoscopic device and / or catheter device can be moved to the new tissue site at 1404. The process of inserting the wire into the tissue site and delivering electroporation can then be repeated at 1406-1414. In some embodiments, the catheter device can be moved to between 1 and about 15 different sites. When the procedure is complete, i.e., if no more tissue sites need to be ablated (1414: NO), and the catheter device was delivered through the working channel of the endoscopic device, the catheter device can optionally be retracted into the working channel at 1416, and the entire assembly including the endoscopic device and catheter device 1418 can be removed from the patient. In embodiments where the catheter device was used independently of the endoscopic device, the wire can be retracted into the catheter shaft, and the catheter device can be removed from the patient at 1418.

[0047]

[0061] As will be appreciated, each of 1402-1018 can be performed using image guidance. For example, the endoscopic device can be configured to capture images of the tissue site and / or catheter device to ensure proper positioning of the catheter device prior to delivering the electroporation. In some embodiments, the endoscopic device can include an imaging channel through which an imaging device extends to capture images of the tissue site and / or catheter device. In some embodiments, a separate imaging device or mechanism can be used to view and confirm the position of the catheter device relative to the tissue and the delivery of the electroporation. In some embodiments, the imaging device (extending through the endoscopic device or separately positioned near the tissue site) can be deflected to capture different views around the tissue site, for example. The imaging modality can include direct optical imaging, ultrasound imaging, or other imaging modalities typically used in the art.

[0048]

[0062] The systems, devices and methods described herein may be implemented in one or more embodiments as described below.

[0049]

[0063] Embodiment 1: A device for ablation delivery, comprising a catheter having at least one distally located distal shaft electrode in the form of a compressible basket, the catheter having a lumen for delivery of a needle device, the needle device having a bulbous tip with a distal sharp point.

[0050]

[0064] Embodiment 2: The basket in one embodiment having a shaft and at least one collar portion for attachment to an electrical lead.

[0051]

[0065] Embodiment 3: A basket made from a superelastic material such as a Nitinol alloy.

[0052]

[0066] Embodiment 4: A needle device that is electrically insulated along a major portion of its length, wherein a section of the length of the distal tapered portion of the needle is conductive and exposed, and the electrical insulation is capable of withstanding at least 300 volts through its thickness without breakdown.

[0053]

[0067] Embodiment 5: A basket attached to an electrically insulated lead wire, wherein the electrical insulation of the lead wire is capable of withstanding at least 300 volts through its thickness without breakdown.

[0054]

[0068] Embodiment 6: A needle device in an embodiment having a bulbous tip including a bulbous portion and at least two tapered portions distal to the bulbous portion, wherein the distal tapered portions converge to a sharp point.

[0055]

[0069] Embodiment 7: A catheter device that can be used for ablation delivery of high voltage pulses, wherein the needle device and the distal shaft electrode are electrically polarized with opposite electrical polarities.

[0056]

[0070] Embodiment 8: A catheter having an outer diameter in the range of about 1 mm to about 6 mm.

[0057]

[0071] Embodiment 9: The maximum diameter of the distal shaft electrode in its relaxed or expanded state is in the range of about 1 mm to about 15 mm.

[0058]

[0072] Embodiment 10: A needle device that, when fully deployed or extended, extends approximately 60 mm beyond the distal tip of the catheter shaft.

[0059]

[0073] Embodiment 11: A spherical portion of the needle distal electrode having a maximum diameter of about 0.4 mm to about 4 mm.

[0060]

[0074] Embodiment 12: The length of the distal tapered portion of the needle device distal to the bulbous portion of the electrode ranges from about 1 mm to about 30 mm.

[0061]

[0075] Embodiment 13: A system comprising a generator and a catheter device for ablation delivery, the catheter device comprising a catheter having at least one distally located distal shaft electrode in the form of a compressible basket, the catheter having a lumen for delivery of a needle device, and the generator capable of delivering high voltage pulses to the distal shaft electrode and the needle device for ablation delivery.

[0062]

[0076] Embodiment 14: A method of use of a catheter device for ablation delivery, comprising a catheter having at least one distally positioned distal shaft electrode in the form of a compressible basket, the catheter having a lumen for delivery of a needle device, the catheter device being introduced into one channel of an endoscopic instrument navigated inside a target anatomical structure, a second channel of the endoscopic instrument being used for imaging of the target anatomical structure, the method comprising extending the catheter device from a distal end of the endoscopic instrument, positioning the catheter device near a target location, extending the needle device from the catheter into the tissue, and delivering high-voltage ablation pulses with the distal shaft electrode and the needle device electrically polarized with opposite electrical polarity.

[0063]

[0077] While specific examples have been provided in the figures for purposes of illustration and depiction, it will be apparent that variations such as, without limitation, different numbers of lumens, different numbers of electrodes, different electrode, catheter and wire diameters, different electrode and shaft materials, etc., may be constructed based on the teachings herein.

[0064]

[0078] Also, various inventive concepts may be embodied as one or more methods, examples of which are provided. The actions performed as part of a method may be ordered in any suitable manner. Thus, embodiments may be constructed in which actions are performed in an order different from that shown, and such embodiments may include performing some actions simultaneously, even though the exemplary embodiments show actions as sequential.

[0065]

[0079] As used herein, the terms "about" and / or "approximately," when used in conjunction with a numerical value and / or range, generally refer to a numerical value and / or range that is close to the recited numerical value and / or range. In some cases, the terms "about" and "approximately" can mean within ±10% of the stated value. For example, in some cases, "about 100 units" can mean within ±10% of 100 (e.g., 90 to 110). The terms "about" and "approximately" can be used interchangeably.

Claims

1. an outer shaft defining a lumen; a first electrode disposed at a distal end of the outer shaft, the first electrode including a compressible basket; an inner shaft slidably positionable within the lumen, the inner shaft includes a distal tip having a bulbous portion and a tapered portion tapering to a distal sharp end; the distal sharp end extends distally relative to the outer shaft and is configured to be inserted into a tissue site; the distal tip includes a second electrode; The first and second electrodes are configured to deliver electroporation to a zone of tissue at the tissue site.

2. Further comprising a lead wire, The device of claim 1 , wherein the compressible basket includes at least one collar portion fixedly attached to the outer shaft and attached to the lead wire.

3. 3. The device of claim 2, wherein the lead is an electrically insulated lead having an insulation layer configured to withstand at least about 300 volts across the thickness of the insulation layer without dielectric breakdown.

4. The device of any one of claims 1 to 3, wherein the compressible basket is formed from a superelastic material.

5. the inner shaft includes an insulating layer covering a substantial majority of an outer surface of the inner shaft; The device of any one of claims 1 to 4, wherein the second electrode is an exposed conductive portion of the distal tip.

6. The device of claim 5 , wherein the exposed conductive portion is disposed at the tapered portion of the distal tip.

7. 6. The apparatus of claim 5, wherein the insulating layer is configured to withstand at least about 300 volts across its thickness without breakdown.

8. the tapered portion is a first tapered portion; the distal tip includes a second tapered portion adjacent to the first tapered portion; The device of any one of claims 1 to 7, wherein the second tapered portion tapers from the bulbous portion toward the proximal end of the first tapered portion.

9. The device of claim 8 , wherein the first tapered portion and the second tapered portion have different tapers.

10. 10. The apparatus of claim 1, wherein the first and second electrodes are configured to be electrically polarized with opposite polarity to deliver electroporation to the zone of tissue.

11. The device of any one of claims 1 to 10, wherein the first and second electrodes are configured to deliver electroporation to ablate the zone of tissue.

12. the first and second electrodes are configured to deliver electroporation to reversibly electroporate the zone of tissue; 12. The device of any one of claims 1 to 11, wherein the inner shaft further comprises a fluid delivery lumen configured to deliver a therapeutic agent to the tissue zone while or after the tissue zone is reversibly electroporated.

13. The device of any one of claims 1 to 12, wherein the outer shaft has an outer diameter of about 1 mm to about 6 mm.

14. The device of any one of claims 1 to 13, wherein the compressible basket has a maximum outer diameter in a relaxed state of about 1 mm to about 15 mm.

15. The device of any one of claims 1 to 14, wherein the inner shaft is configured to extend up to about 60 mm beyond the distal tip of the outer shaft when fully deployed.

16. The device of any one of claims 1 to 15, wherein the bulbous portion of the distal tip has a maximum diameter of about 0.4 mm to about 4 mm.

17. The device of any one of claims 1 to 16, wherein the portion of the distal tip distal to the bulbous portion is between about 1 mm and about 30 mm.

18. an outer shaft defining a lumen; a ring electrode disposed at a distal end of the outer shaft; an inner shaft slidably positionable within the lumen, the inner shaft includes a distal tip having a bulbous portion and a tapered portion tapering to a distal sharp end; the distal sharp end extends distally relative to the outer shaft and is configured to be inserted into a tissue site; the distal tip includes an exposed conductive portion; The device, wherein the ring electrode and the exposed conductive portion are configured to deliver electroporation to a zone of tissue at the tissue site.

19. 20. The device of claim 18, further comprising one or more additional ring electrodes disposed adjacent the ring electrode at the distal end of the outer shaft.

20. 20. The device of any one of claims 18 to 19, wherein the inner shaft includes an insulating layer covering the outer surface of the inner shaft everywhere except the exposed conductive portion.

21. 21. The apparatus of claim 20, wherein the insulating layer is configured to withstand at least about 300 volts across its thickness without dielectric breakdown.

22. The device of any one of claims 18 to 21, wherein the exposed conductive portion is located at the tapered portion of the distal tip.

23. the tapered portion is a first tapered portion; the distal tip includes a second tapered portion adjacent to the first tapered portion; The device of any one of claims 18 to 22, wherein the second tapered portion tapers from the bulbous portion toward the proximal end of the first tapered portion.

24. 24. The device of claim 23, wherein the first tapered portion and the second tapered portion have different tapers.

25. 25. The device of any one of claims 18 to 24, wherein the ring electrode and the exposed conductive portion are configured to be electrically polarized with opposite polarities to deliver electroporation to the zone of tissue.

26. 26. The device of any one of claims 18 to 25, wherein the ring electrode and the exposed conductive portion are configured to deliver electroporation to ablate the zone of tissue.

27. the ring electrode and the exposed conductive portion are configured to deliver electroporation to reversibly electroporate the zone of tissue; 27. The device of any one of claims 18 to 26, wherein the inner shaft further comprises a fluid delivery lumen configured to deliver a therapeutic agent to the tissue zone while or after the tissue zone is reversibly electroporated.

28. a catheter device including a shaft and a needle; a pulse generator configured to be coupled to the catheter device; the shaft defines a lumen configured to slidably receive the needle such that the needle can be advanced distally therethrough and penetrate into a tissue site; the shaft includes a distally located first electrode having a compressible basket; the needle includes a distally located second electrode; The system, wherein the pulse generator is configured to generate and deliver voltage pulses to the catheter device such that the first and second electrodes are polarized with opposite polarities to deliver electroporation to a tissue zone at the tissue site.

29. 30. The system of claim 28, wherein the voltage pulse has an amplitude of at least about 700 volts.

30. The system of any one of claims 28 to 29, wherein the needle includes a bulbous portion and a tapered portion tapering to a distal sharp tip.

31. the tapered portion is a first tapered portion; 31. The system of claim 30, wherein the needle includes a second tapered portion adjacent the first tapered portion and tapering from the bulbous portion toward the proximal end of the first tapered portion.

32. 32. The system of claim 31, wherein the first and second tapered portions have different tapers.

33. 31. The system of claim 30, wherein the second electrode is an exposed conductive portion of the tapered portion of the distal tip.

34. 31. The system of claim 30, wherein the needle includes an insulating layer covering a substantial majority of an outer surface of the needle.

35. 35. The system of claim 34, wherein the insulating layer is configured to withstand at least about 300 volts across its thickness without dielectric breakdown.

36. 36. The system of any one of claims 28 to 35, wherein the compressible basket includes at least one collar portion fixedly attached to the shaft and attached to a lead wire disposed therein.

37. The system of any one of claims 28 to 36, wherein the compressible basket is formed from a superelastic material.

38. further comprising an endoscopic device; The system of any one of claims 28 to 37, wherein the endoscopic device includes a working channel configured to slidably receive the catheter device such that the endoscopic device can deliver the catheter device within the working channel to the tissue site.

39. the endoscopic device further defines a lumen for receiving an imaging device; 40. The system of claim 38, wherein the imaging device is configured to capture views near the tissue site to confirm positioning of the catheter device.

40. positioning a catheter device near a tissue site, the catheter device including a shaft and a needle slidably disposed therein, the shaft including a distally positioned first electrode having a compressible basket; extending the needle distally from the shaft to insert the distal tip of the needle into a tissue site, the distal tip of the needle including a second electrode; delivering voltage pulses to the first and second electrodes to electroporate a zone of tissue at the tissue site; A method comprising:

41. inserting the catheter device through a lumen of an endoscopic device; 41. The method of claim 40, further comprising navigating the endoscopic device to the tissue site to position the catheter proximate the tissue site.

42. the lumen is a first lumen, and the endoscopic device further includes a second lumen configured to receive an imaging device; The method comprises: inserting the imaging device into the second lumen such that the imaging device is positioned proximate the tissue site; 42. The method of claim 41, further comprising capturing one or more views of an area surrounding the tissue site to confirm the positioning of the catheter device.

43. 43. The method of any one of claims 40 to 42, wherein delivering the voltage pulse comprises delivering the voltage pulse with the first and second electrodes having opposite polarities.

44. 44. The method of any one of claims 40 to 43, wherein the voltage pulse has an amplitude of at least about 700 volts.

45. the tissue site is a first tissue site; The method comprises: retracting the needle from the tissue site after delivering the voltage pulse; moving the catheter device to a second tissue site; extending the needle into the second tissue site; 45. The method of any one of claims 40-44, further comprising delivering a voltage pulse to the first and second electrodes to electroporate a zone of tissue at the second tissue site.

46. 46. ​​The method of any one of claims 40 to 45, further comprising delivering a therapeutic agent to the tissue zone through the needle lumen.

Images