Multi-wound electrode therapy system and method

Abstract

Apparatus, systems, and methods for controlled delivery of electrolytes and cell permeation therapy to tissue sites are disclosed. The systems, apparatus, and methods may include designs having features for efficiently deploying a flexible substrate with electrodes at the tissue site for treatment and for facilitating the retraction of the electrodes back into a housing for removal after treatment. The systems, apparatus, and methods may further include expansion members for radially expanding the flexible substrate to aid in positioning the electrodes adjacent to tissue to facilitate treatment.

Description

[0001] Cross-reference to related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 584,669, filed September 22, 2023, pursuant to 35 USC § 119(e) (which is incorporated herein by reference in its entirety). Technical Field

[0002] This disclosure generally relates to the field of tissue treatment. Specifically, this disclosure relates to apparatus and methods having deployable electrodes for ablating cells to treat targeted tissues. Background Technology

[0003] In vivo tissue can be treated by excision and removal during surgical or medical procedures. While such procedures may be necessary for treating larger lesions or addressing a variety of medical conditions, minimally invasive procedures can be used as an alternative in certain situations. Such procedures, when applicable, may be more beneficial than more invasive procedures in reducing overall patient risk, damage to surrounding tissues, recovery time, discomfort, and potential harmful side effects. In minimally invasive tissue ablation, targeted tissue can be treated in vivo (e.g., in situ) using procedures that do not involve excision or may require minimal excision. Some examples of minimally invasive tissue ablation techniques include electrolytic ablation, cryosurgery, chemical ablation (e.g., alcohol injection), thermal ablation (e.g., radiofrequency, microwave), and hydrothermal ablation. The primary purpose of these ablation procedures is to destroy abnormal tissue in the target area and promote the regeneration of healthy tissue.

[0004] Another known minimally invasive treatment technique involves electroporating the target tissue by applying a local electric field to increase cell membrane permeability, thus allowing drugs or other chemicals to be introduced into the cells for treatment. Electroporation can also be used in combination with electrolysis, a process also known as electrolytic electroporation, electroporation-electrolysis, or E2, as a method of tissue ablation.

[0005] Tissue ablation is a therapeutic procedure used to treat various tissue injuries, including those in the gastrointestinal tract. Damage to intestinal tissue can be caused by several factors, but is often associated with chronic metabolic disorders such as diabetes. In people with diabetes, damage to the gastrointestinal tract, particularly the duodenum, can lead to insulin resistance and / or impaired ability to process glucose. To help manage this disorder, duodenal mucosal resurfacing (DMR) can be used to reconstruct the intestinal lining, aiming to help regenerate a healthy lining and improve nutrient absorption in the duodenum. Improved intestinal lining health can help correct absorption problems and enable some patients to respond better to insulin therapy, which in turn can allow patients to manage their condition by using oral medications instead of more invasive insulin therapies (e.g., injections).

[0006] Generally, DMR (Disseminated Minimal Ablation) is a procedure involving the introduction of a catheter (or other suitable medical device system) with an inflatable balloon (or other expansion member) into the duodenum, typically under endoscopic guidance. In one exemplary configuration, the balloon supports a flexible substrate on which electrodes are disposed, wherein the electrodes are configured to deliver energy to ablate a target tissue area at a controlled depth. Once the catheter is advanced to the target area for treatment, the balloon is inflated to expand the flexible substrate and position the electrodes near (or in contact with) the tissue. The electrodes are then energized to ablate the target tissue. After treatment at the first tissue site is completed, the catheter can be repositioned to other tissue areas and the ablation process can be repeated multiple times as needed to treat larger tissue areas.

[0007] The inventors recognized the need for an improved electrode therapy system for electroporation and / or electrolysis to ablate cells for the treatment of targeted tissues. Some aspects of the improved electrode therapy system include a flexible substrate wound into two separate furled segments to reduce the overall profile of the electrode therapy system for compact delivery to the target tissue site. When deployed, the flexible substrate maintains a sufficiently large surface area to support a suitable electrode for treatment. Additionally, the electrode therapy system may include extension members operable to expand the flexible substrate to ensure proper electrode positioning relative to the tissue for effective treatment. Other aspects of the improved electrode therapy system include features that independently and / or simultaneously drive each furled segment of the flexible substrate to increase overall design flexibility for therapeutic purposes and facilitate the flexible substrate retracting to a compact furled position after treatment. Additional aspects and advantages of such a system will become apparent from the following detailed description of exemplary embodiments with reference to the accompanying drawings. Summary of the Invention

[0008] This document describes various examples of electrode therapy systems for treating tissue. An exemplary system may include a housing and a first and a second drive element, each drive element having a distal portion extending into the housing. The system further includes a flexible substrate on which electrodes are disposed, the flexible substrate having a first portion coupled to the distal portion of the first drive element and a second portion coupled to the distal portion of the second drive element, wherein when the flexible substrate is in a retracted position, a first retracted section of the flexible substrate surrounds the distal portion of the first drive element and a second retracted section of the flexible substrate surrounds the distal portion of the second drive element. In one exemplary configuration, the first and second retracted sections are laterally offset from each other within the housing. In some exemplary systems, counter-rotation of the first and second drive elements relative to each other unfolds the first retracted section from the first drive element and unfolds the second retracted section from the second drive element to deploy the flexible substrate from the retracted position to an extended position for treatment.

[0009] In some exemplary systems, when the flexible substrate is in the retracted position, a segment of the flexible substrate extends between the first retracted segment and the second retracted segment. In some exemplary systems, the first retracted segment and the second retracted segment are wound around respective first and second drive elements in opposite directions relative to each other to facilitate deployment and retraction.

[0010] In some exemplary systems, the housing includes a working channel with an opening on its distal side. The working channel includes a first seat for receiving a first retracted segment of the flexible substrate when the flexible substrate is in the retracted position, and a second seat for receiving a second retracted segment of the flexible substrate. In some exemplary systems, the first and second driving elements are axially movable relative to the housing to drive the first and second retracted segments, respectively, through the opening in the working channel and toward the distal side of the housing. In this configuration, the first and second driving elements are actuated to deploy the flexible substrate from the retracted position to the extended position.

[0011] In some exemplary systems, the system further includes a sheath disposed within the housing, the sheath including a first seat for receiving a first retracted segment of the flexible substrate when the flexible substrate is in the retracted position and a second seat for receiving a second retracted segment of the flexible substrate. The housing may further include a working channel, wherein the sheath is coupled to the working channel. In some exemplary systems, the first and second drive elements are axially movable relative to the housing to drive the first and second retracted segments, respectively, through the openings in the sheath and the working channel and toward the distal side of the housing. When the first and second retracted segments are positioned distally to the housing, the first and second drive elements may be actuated to deploy the flexible substrate from the retracted position to the extended position.

[0012] In some exemplary systems, the first driving element and the second driving element can be actuated independently of each other, such that, between the retracted position and the extended position, the first driving element drives the first retracted segment of the flexible substrate and the second driving element drives the second retracted segment of the flexible substrate independently of each other. The first driving element can be connected to a first driver and the second driving element can be connected to a second driver, wherein the first driver and the second driver can operate independently of each other.

[0013] In some exemplary systems, the system may further include a drive system coupled to one of the first drive element and the second drive element, the drive system being operable to rotate one of the first drive element and the second drive element in a first direction. The system may further include a gear system coupling the first drive element and the second drive element to each other, wherein the gear system causes the other of the first drive element and the second drive element to rotate in a second direction opposite to the first direction.

[0014] In some exemplary systems, the outer diameter of the flexible substrate in the extended position ranges from 3:1 to 6:1 compared to the corresponding outer diameter of each of the first and second folded sections when the flexible substrate is in the folded position.

[0015] Another exemplary system may include a housing, a first drive element rotatable about a rotation axis and having a distal portion extending into the housing, and a second drive element having a distal portion extending into the housing. The system may further include a flexible substrate on which electrodes are disposed, the flexible substrate having a first portion coupled to the distal portion of the first drive element and a second portion coupled to the distal portion of the second drive element, wherein when the flexible substrate is in a retracted position, a first retracted segment of the flexible substrate surrounds the distal portion of the first drive element and a second retracted segment of the flexible substrate surrounds the distal portion of the second drive element. In one exemplary configuration, the first and second retracted segments are laterally offset from each other within the housing. In some exemplary systems, rotation of the first drive element about the rotation axis both unfolds the first retracted segment from the first drive element and unfolds the second retracted segment from the second drive element to deploy the flexible substrate from the retracted position to the extended position. In some exemplary systems, the second drive element is non-rotatable relative to the first drive element.

[0016] In some exemplary systems, the first driving element is coupled to a driving system operable to rotate the first driving element about the rotation axis in a first rotational direction to deploy the flexible substrate from the retracted position to the extended position. The driving system may further be operable to rotate the first driving element about the rotation axis in a second rotational direction opposite to the first rotational direction to retract the flexible substrate from the extended position back to the retracted position.

[0017] In some exemplary systems, the system further includes an extension member extending outward from the housing, along its distal side, and through a first opening in the working channel. The extension member engages the flexible substrate in the extended position, wherein the extension member can extend radially to further extend the flexible substrate from the extended position to a second extended position. The housing may further include a second working channel having a second opening on the distal side of the housing, the second opening being offset from the first opening of the first working channel. The first drive element and the second drive element are axially movable relative to the housing to drive the first retractable segment and the second retractable segment, respectively, through the second opening of the second working channel and toward the distal side of the housing.

[0018] Another exemplary system may include a housing and a first drive element and a second drive element, each drive element having a distal portion extending into the housing. The system further includes a flexible substrate on which electrodes are disposed, the flexible substrate having a first portion coupled to the distal portion of the first drive element and a second portion coupled to the distal portion of the second drive element, wherein when the flexible substrate is in a retracted position, a first retracted segment of the flexible substrate surrounds the distal portion of the first drive element and a second retracted segment of the flexible substrate surrounds the distal portion of the second drive element. In this configuration, the first and second retracted segments are laterally offset from each other within the housing. In some exemplary systems, rotation of one or both of the first and second drive elements unfolds the first retracted segment from the first drive element and unfolds the second retracted segment from the second drive element to deploy the flexible substrate from the retracted position to a first extended position. The system further includes an extension member that engages the flexible substrate when in the first extended position, wherein the extension member is radially extendable to further extend the flexible substrate from the first extended position to a second extended position.

[0019] In some exemplary systems, the housing includes a first working channel having a first opening on a distal side of the housing, wherein the extension member is axially movable relative to the housing and extends distally thereto through the first opening of the first working channel. The housing may further include a second working channel having a second opening on the distal side of the housing, wherein a first drive element and a second drive element are axially movable relative to the housing to drive a first retractable segment and a second retractable segment distally thereto, respectively, through the second opening of the second working channel. The first opening of the first working channel may be offset from the second opening of the second working channel along the distal side of the housing.

[0020] In some exemplary systems, the counter-rotation of the first drive element relative to the second drive element simultaneously unfolds the first folded section from the first drive element and the second folded section from the second drive element. In some exemplary systems, after the flexible substrate is deployed to the second extended position, further rotation of one or both of the first and second drive elements retracts the flexible substrate from the second extended position back to the folded position.

[0021] In some exemplary systems, the outer diameter of the flexible substrate in the first extended position ranges from 3:1 to 6:1 compared to the corresponding outer diameter of each of the first and second retracted sections when the flexible substrate is in the retracted position. In some exemplary systems, the outer diameter of the flexible substrate in the second extended position is larger than that in the first extended position.

[0022] It should be understood that the foregoing overview provides various examples for further description herein and is not intended to identify any key or essential aspects of the disclosed or claimed subject matter. Furthermore, aspects of the exemplary systems outlined above can be combined in any suitable manner without departing from the principles of the disclosed or claimed subject matter. Attached Figure Description

[0023] The above and other features of this disclosure will become more apparent from the accompanying drawings, the following description, and the appended claims. It should be understood that these drawings depict only a few examples according to this disclosure and are therefore not intended to be limiting of the scope. The disclosure will be described with additional specificity and detail using the drawings, in which: Figure 1 This is a schematic illustration of an electroporation and / or electrolysis system based on the examples described herein.

[0024] Figure 2 This is a schematic illustration of a robot-assisted manipulator system based on the examples described herein.

[0025] Figure 3A This is a schematic diagram of a medical device system based on the example described in this article.

[0026] Figure 3B Examples based on the description in this article are shown. Figure 3A The distal portion of a medical device system having an extension of the device.

[0027] Figure 4 An electrode therapy system for delivering a flexible substrate with electrodes (shown in a collapsed position) to a target area for treatment, according to an example described herein, is shown.

[0028] Figure 5 yes Figure 4 An enlarged end view of the distal portion of the electrode therapy system.

[0029] Figure 6 yes Figure 4 Enlarged front view of the distal portion of the electrode therapy system.

[0030] Figure 7 The flexible substrate shown in the example described herein is in an extended position. Figure 4Electrode therapy system.

[0031] Figure 8 Examples based on the description in this article are shown. Figure 4 The support structure of the electrode therapy system.

[0032] Figure 9 Another example of an electrode therapy system is shown for delivering a flexible substrate with electrodes to a target area for treatment. The electrode therapy system includes a gear system for controlling a drive element coupled to the flexible substrate.

[0033] Figure 10 Another example of an electrode therapy system for delivering a segmented flexible substrate with electrodes to a target area for treatment, according to the example described herein, is shown.

[0034] Figure 11 Another example of an electrode therapy system for delivering a flexible substrate with electrodes to a target area is shown, the electrode therapy system including an extension member for assisting in extending the flexible substrate to an extended location. Detailed Implementation

[0035] Certain details are set forth below to provide a full understanding of embodiments of this disclosure. However, it will be apparent to those skilled in the art that embodiments of this disclosure may be practiced without these specific details. Furthermore, the specific examples of this disclosure described herein are provided by way of example and should not be intended to limit the scope of the claimed subject matter to these specific embodiments. In other instances, well-known materials, components, processes, controller components, software, and / or anatomy have not been described or shown in detail to avoid unnecessarily obscuring these embodiments.

[0036] This disclosure relates to devices and systems for the controlled delivery of one or more pairs of electrodes to a target tissue site for treatment via electroporation and / or electrolysis. Generally, a method for minimally invasive regenerative surgery is disclosed, comprising subjecting a target region in living tissue to a combination of one or more electric fields and electrolysis delivered via the one or more pairs of electrodes. In some examples, the ablation energy may be in the form of a combination of one or more electric fields and electrolysis. However, it should be understood that the exemplary systems and methods described herein can be used to deploy flexible substrates carrying electrodes using ablation modalities other than electroporation and / or electrolysis (e.g., radiofrequency ablation), or for purposes other than ablation, such as electrical stimulation or other diagnostic methods.

[0037] During the exemplary procedure, electrodes are brought close to and / or contacted with the target tissue, and an electric field is generated by applying voltage and / or current between the one or more pairs of electrodes. An electric field of a certain magnitude can be generated to permeate cell membranes in the area to be ablated. An electric field can be generated to produce electrolytic products of a magnitude that itself does not damage cells or the extracellular matrix. However, when sufficient electrolytic products are generated in the permeable cell region, cell death occurs in the field application region without damaging the extracellular matrix or scaffold structure, thereby helping to promote tissue regeneration in the treated tissue region.

[0038] In some examples, the electrodes can be moved to other tissue locations by advancing and / or retracting them as needed and repeating the process. In this way, electroporation and / or electrolysis can be performed at multiple locations within the patient to cover a larger area of ​​tissue. In some examples, multiple sets of electrodes can be positioned at multiple corresponding tissue sites, allowing electroporation and / or electrolysis to be performed in parallel at various sites, thereby reducing and / or eliminating the need to repeat the procedure when catheters, endoscopes, or other suitable medical devices move through the patient.

[0039] In some embodiments of this disclosure, the systems and methods disclosed herein can be used to treat gastrointestinal tissues. In other embodiments, the systems and methods described herein can be used to treat any tissue among a variety of tissues. Generally, tissues can be treated when tissue regeneration is desired or when it is desired to replace one type of cell with another. Examples include the intestine, duodenum, stomach, bladder, uterus, endometrium, ovary, colon, rectum, sinus, duct, ureter, prostate, skin, muscle, nerve, diaphragm, momentum, kidney, follicle, brain, lymphatic vessels, breast, esophagus, lung, liver, kidney, lymph nodes, lymph node pelvis, and / or heart. Replacing one type of tissue with another can occur in fibrotic areas (where it is desired to replace fibrotic cells with stem cells that can reprogram the area) or when islets of Langerhans are injected into a portion of the liver to generate a new source of insulin. In other examples, other tissues can be treated. Additional details related to exemplary processes of electroporation and / or electrolysis for tissue treatment according to some embodiments are provided below.

[0040] As described above, electroporation can be performed to permeate the cell membrane of targeted cells. Reversible electroporation can be employed, where permeation can be stopped after the electric field is removed. Cells can survive in reversible electroporation while the pores within the membrane reseal and homeostasis is restored. However, in some therapeutic procedures, electrolytes can be applied to permeated cells to kill the permeated cells within the applied electric field, while maintaining the integrity of the extracellular matrix of the permeated cells. The extracellular matrix generally refers to a three-dimensional network of proteins and / or other molecules (e.g., collagen fibers, proteoglycans, and / or proteins such as fibronectin and / or laminin) that provides structure for cells and tissues and can also provide signaling for cell growth and development. The extracellular matrix can be used as a scaffold for tissue regeneration and / or engineering. For example, cells can be regenerated, grown, transplanted, or otherwise cultured on the extracellular matrix. Cell regeneration and / or tissue engineering can occur in the ablated cell regions by retaining the extracellular matrix within additional ablated cell regions described herein. In some procedures, extracellular matrix can be transplanted from one ablated cellular region to another (which may be another region of ablated cells) to promote regeneration and / or tissue engineering of the transplanted region. In some cases, material can be injected into the extracellular matrix once it is present to enhance regrowth.

[0041] The exemplary systems and methods described herein can permeate cell membranes by utilizing electrolytic products and electroporation to induce cell death. The electrolytic products are sufficient to ablate (e.g., induce cell death) permeable cells within a relatively short timeframe. However, the concentration and exposure time of the electrolytic products are insufficient to induce cell death in unpermeable cells, thereby minimizing or avoiding the formation of scar tissue, fibrosis, or ulceration in the treatment area. Scar tissue and fibrosis indicate that the extracellular matrix has been affected, and the ability of cell regeneration and / or tissue engineering to occur in the ablation area may be inhibited. Therefore, the electrolytic products are used only to ablate permeable cells while maintaining the integrity of the extracellular matrix to promote tissue regeneration. Electrolytic products may include cytotoxic products. In addition to acting as an electron source or sink or as a catalyst, electrolysis preferentially employs one or more inert electrodes that do not participate in the electrolysis process. When non-inert electrodes are used in this process, they can generate metal ions that may cause systemic damage to the body, such as excess iron or even metal fragments.

[0042] Examples of systems disclosed herein include one or more electrodes, a power source, and a controller to apply energy for treating internal tissue. The applied energy may be used for electrolysis and / or electroporation in some examples, for radiofrequency ablation in others, and for other energy modes in still others. When energy is used for electroporation in the presence or absence of electrolysis, the controller controls the charge delivered to the electrodes(s) to induce one or more electric fields. In cases involving both electroporation and electrolysis, the electrodes(s) are used to generate a current to produce electrolytic products and to generate a voltage difference to produce an electric field that initiates electroporation. The duration and magnitude of the applied charge determine the dose of the electrolytic products and the degree of cell permeation in the treatment site. Therefore, the cell ablation zone can be determined by the area where cells are exposed to a combination of permeation and electrolytic products that induce ablation. However, ablation can maintain the integrity of the extracellular matrix in the ablated cell region where an electric field has been applied. The composition of the electrodes can be selected based on the desired products and electroporation effects produced.

[0043] Examples of the systems and methods described herein can leverage the combination of electroporation and electrolysis to facilitate more effective tissue ablation and promote tissue regeneration in the treatment area. Electroporation, which involves permeating the cell membrane by applying an electric field across the cell membrane, can achieve tissue ablation using two different sets of electrical parameters: one set for reversible electroporation and the other for irreversible electroporation. As previously mentioned, reversible electroporation is the permeation of the cell membrane, which typically stops upon removal of the electric field and in which the cells survive after the application of the electric field. In irreversible electroporation, the permeation of the cell membrane is permanent, leading to cell death. Therefore, some electrical parameters produce irreversible electroporation, in which the pores formed in the cell membrane do not reclose after the removal of the electric field, and the permeation becomes permanent, leading to electroporated cell death. Generally, for biological tissues, electric fields below approximately 1500 V / cm to approximately 200 V / cm are considered to produce reversible electroporation, while electric fields above approximately 1500 V / cm are considered to produce irreversible electroporation. The examples of the systems and methods described herein can utilize reversible electroporation to avoid the drawbacks of irreversible electroporation, which can include heating and thermal damage, the complexity of providing such a large electric field, and muscle contraction that may be induced by the large electric field. It should be understood that while the systems and methods described herein can be designed to utilize reversible electroporation, there may also be locations or regions where conditions make irreversible electroporation, or even thermal ablation, possible in a limited portion of the treated tissue.

[0044] In summary, the examples of systems and methods described herein utilize reversible electroporation to permeate cells within a target region for ablation. The electric field and / or other electric fields used to generate the reversible electroporation can be used to produce electrolytic products. These products are introduced into the target region to induce ablation only of permeated cells (e.g., by diffusion across the permeation membrane) without affecting unpermeable cells and the extracellular matrix. The quantity, concentration, and intensity of the provided electrolytic products ensure that the extracellular matrix in the permeated and ablated cellular region remains intact, and that unpermeable cells survive treatment that promotes tissue regeneration. One objective of combining cell membrane permeation with electrolytic therapy is to minimize or avoid severe inflammation, ulceration, and necrosis of the tissue at the treatment site, which in turn reduces or eliminates the formation of scar and fibrotic tissue and leaves a decellularized extracellular matrix suitable for promoting and supporting the regeneration of healthy tissue.

[0045] refer to Figure 1 The following provides a brief overview of an exemplary system for delivering an electrode-bearing medical device to a target tissue site for treatment via electroporation and / or electrolysis. Figure 1 This is a schematic illustration of a system 10 arranged according to the exemplary embodiments described herein. Generally, the exemplary system described herein may include a delivery system and a controller. Figure 1 In this example, system 10 includes controller 14 and medical device system 40. Examples of other medical device systems that can be used with system 10 (or other suitable systems described herein) are referenced below. Figures 4-11 Further detailed description is provided below. As further described below, controller 14 may include processor 16, computer-readable medium 18, 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. Computer-readable medium 18 includes executable instructions for inducing electroporation and / or electrolysis through medical device system 40, and may include stored parameters 22 that can be used during the induction of electroporation and / or electrolysis, such as electric field strength, voltage and / or current levels, waveform shape, exposure duration parameters, and any other suitable parameters. Figure 1 In the example, the circle drawn around one end of the medical device system 40 can indicate a cellular region that can be permeated by an applied electric field.

[0046] Controller 14 can be implemented using a computing device. Examples of computing devices include controllers, microcontrollers, computers, servers, medical devices, smartphones, tablets, wearable devices, etc. The computing device can be handheld and may also have other uses. Controller 14 may include one or more processors, such as processor 16. Any type or number of processors may be present, including one or more central processing units (CPUs) or graphics processing units (GPUs) having any number of cores, controllers, microcontrollers, and / or custom circuitry, such as one or more application-specific integrated circuits (ASICs) and / or field-programmable gate arrays (FPGAs).

[0047] The controller 14 described herein may include a computer-readable medium 18, such as memory. Any type or kind of memory may be present (e.g., read-only memory (ROM), random access memory (RAM), solid-state drive (SSD), secure digital card (SD card), etc.). Although in Figure 1 A single box is depicted as computer-readable medium 18, but any number of computer-readable medium 18 devices may exist. Computer-readable medium 18 may communicate with processor 16 (e.g., be electrically connected to processor 16).

[0048] As described above, the computer-readable medium 18 may store executable instructions (such as executable instructions for inducing electroporation and / or electrolysis 20 with the medical device system 40) that can be executed by the processor 16, and may utilize the stored parameters 22 of the medical device system 40. In this way, the technique of applying electroporation and / or electrolysis in tissue can be implemented wholly or partially in software.

[0049] Executable instructions 20 may include instructions to control the delivery of charge to an electrode (such as electrode 50 of medical device system 40). Therefore, controller 14 can sense a voltage difference across the target tissue to generate an electric field that causes permeation of cells in the targeted therapeutic tissue region. In the illustrated embodiment, electrode 50 may be positioned as specifically referenced. Figures 4-7 The medical device system 400 further describes in detail the flexible substrate of the medical device system 40 (e.g., Figure 4 The electrode 50 is shown located on a flexible substrate 422. The electrode 50 is shown located in a cavity or cavity 32 formed within the tissue 30. Although the medical device system 40 is shown to be disposed within a cavity 32 of the tissue 30, the medical device system 40 may be on the surface of the tissue 30, inside the tissue 30, and / or near the tissue 30.

[0050] Controllers, such as Figure 1The controller 14 can activate one or more selected electrodes 50 to provide an electric field. In some embodiments, the controller 14 can alternately or otherwise select a mode of activated electrodes 50 (e.g., sequentially activating electrode pairs) to shape or deliver a specific electric field. In some examples, a fluid or other substance may be injected into, contacted with, or otherwise placed in or around tissue 30 to help shape the electric field generated in tissue 30. For example, a conductive fluid can help shape the field (e.g., by spreading the field). In other examples, a non-conductive fluid can help shape the field (e.g., by attenuating the field). In some examples, a non-conductive fluid or other substance may be injected or otherwise placed into tissue to protect areas not intended for ablation. The electric field may not penetrate and / or pass through the non-conductive fluid, such that the field does not reach tissue not intended for ablation, or at least is insufficient in intensity to cause permeation or other cellular changes.

[0051] The controller 14 can also be used to sense current passing through tissue 30 (such as between electrodes 50) to generate an electrolytic product. The electrolytic product can cause ablation of permeable cells, but preferably not enough to destroy the extracellular matrix in the permeable cell region. As previously described, the remaining intact extracellular matrix can allow for tissue regeneration and tissue engineering.

[0052] In some embodiments, one or more of the electrodes 50 used to apply electroporation may also be used to generate electrolytic products (in other words, some or all of the electrodes may be used for electroporation and / or electrolysis of both). In other embodiments, the first subset of electrodes 50 used to apply electroporation may be different from the second subset of electrodes 50 used to generate electrolytic products.

[0053] In some embodiments, power supply 12 is integrated with controller 14. Power supply 12 can be implemented using any suitable power source, such as one or more AC power supplies, DC power supplies, batteries, and / or waveform generators. Power supply 12 can supply power to electrode 50 to generate voltage and / or current, and thus generate electric fields and / or electrolytic products in tissue 30. In some examples, power supply 12 can be implemented using a signal generator, such as an exponentially decaying wave generator (for example, Harvard Apparatus BTX 630), however, this disclosure is not limited thereto.

[0054] Controller 14 can control the timing, intensity, and duration of the electric field and / or electrolytic products provided via medical device system 40. Controller 14 can, for example, be programmed to provide electrical signals to medical device system 40 via power supply 12, wherein the electrical signals can indicate therapeutic doses, such as the dose of electrolytic products and / or the permeation level of cells. The electrical signals can control the timing and magnitude of the generated electric field, which can allow a user to customize treatment of tissue 30 as desired. In some embodiments, controller 14 may include such a program, or include one or more processing means (e.g., processors) coupled to a computer-readable medium 18 encoded with electrolysis and permeation executable instructions 20. Although in Figure 1 While shown as a separate component coupled to the medical device system 40, in some embodiments, the controller 14 may be integrated as part of the medical device system 40. In other embodiments, the controller 14 may include programmable circuitry coupled to the medical device system 40 via a wired or wireless connection.

[0055] As previously described, system 10 may include any suitable parameters 22 for controlling various aspects of the electroporation and / or electrolysis process, such as electric field strength, voltage level, current level, waveform shape, exposure duration parameters, and any other suitable parameters. Parameters 22 may be stored in computer-readable medium 18 or in another suitable database in communication with controller 14. In some embodiments, controller 14 may be used to calculate parameters 22, or controller 14 may communicate with other systems operable to calculate parameters 22.

[0056] In some exemplary embodiments, parameters 22 of a specific treatment regimen can be determined based on measurements obtained in the tissue of interest or from different samples of similar tissues. For example, measurements can be obtained at various voltage levels with specific electrode configurations, and target voltage levels, currents, pulse patterns, time constants, and other factors that lead to reversible electroporation and the delivery of electrolysis products, thereby inducing cell death in permeable cells as desired.

[0057] In some embodiments, examples of parameters 22 that can be used include the delivery of 1 to 50 voltage pulses between 50 V and 1000 V. Those pulses can have a voltage range of 50 V. F and 1000 The system is supplied with capacitance between F and resistance between 15-20 ohms. The amount of electrolytic product generated can be related to the transferred charge, measured in coulombs. There are several ways to calculate the transferred charge. For example, the charge Q (in coulombs, abbreviated C) stored in a capacitor is equal to the product of the capacitor's capacitance C (in farads, abbreviated F) and the voltage V (in volts, abbreviated V) across its terminals. That is, Q = C·V. Furthermore, current x time = charge. It = Q. By defining capacitance and the voltage across the capacitor, charge can be defined, and electrolytic performance can be determined accordingly. When a capacitor discharges, it generates a current, and the current multiplied by time must equal the charge in the capacitor. When a capacitor is positively discharging, the current is not constant—it decays exponentially. Therefore, the time measure is given as an exponentially decaying time constant. The capacitance controlling the time constant is usually determined by the capacitor connected in parallel to the power source (such as...). Figure 1 The capacitor in power supply 12) is obtained.

[0058] In some embodiments, the time constant (e.g., the exponential decay time constant of capacitor discharge) can range from 50 µs to 3 ms. Generally, the lower limit of the time constant relates to the time sufficient to ensure that the electrolyte (e.g., electrolyte products) permeates the target region of the permeable cell. The upper limit of the time constant generally relates to the generation of the electrolyte (e.g., electrolyte products) that itself would cause ablation. Therefore, electrolysis should generally be targeted to allow sufficient time for electrolyte products to diffuse through the permeable cell region. However, the amount of time provided for electrolysis should be limited to ensure that the process does not lead to the ablation of unpermeable cells or otherwise damage the extracellular matrix in the ablated cell region.

[0059] In some embodiments, the generated electric field ranges between 100 V / cm and 3500 V / cm. In other embodiments, the electric field can be between 100 V / cm and 1500 V / cm, or between 200 V / cm and 850 V / cm. In still other embodiments, the electric field can be less than 1400 V / cm in some examples, less than 1300 V / cm in some examples, less than 1000 V / cm in some examples, less than 800 V / cm in some examples, or less than 600 V / cm in some examples.

[0060] System 10 may also include one or more sensors (not shown) for measuring the pH, electric field strength, and / or other suitable properties of tissue 30 to optimize treatment. For example, in one embodiment, a pH sensor may be integrated with system 10. The pH sensor may be arranged in any of several configurations, such as being coupled to a medical device system 40 adjacent to electrode 50 to detect pH values ​​near electrode 50. In another embodiment, the pH sensor may be provided at the outer edge of the targeted tissue region. In any configuration, the pH sensor may communicate with controller 14, which may utilize one or more received pH values ​​as an indication of tissue ablation and / or monitor the occurrence of tissue damage based on pH levels detected at the treatment site and around the tissue region. In some embodiments, controller 14 may adjust the voltage, current, and / or electric field applied to the tissue in response to the detected pH level. For example, if the pH value of tissue located outside the treatment site is at or above a threshold for tissue damage, controller 14 may reduce the magnitude of the electric field, the duration between pulses, or stop applying the electric field. Similarly, if the pH of the tissue in the target area is at or above the threshold for tissue ablation, the controller 14 can immediately and / or stop the electrolysis process by stopping the application of current through the electrodes after the desired elapsed electrolysis time.

[0061] In some embodiments, a resistivity meter can be used to determine the resistance of a target tissue. For example, Figure 1 The controller 14 and / or power supply 12 can provide impedance measurements. Impedance measurements can determine the resistivity of the tissue 30 contacted by the electrodes 50 of the system 10. For example, the controller 14 and / or power supply 12 can provide a nominal amount of current (such as DC current) through the tissue 30 and receive resistivity measurement results and / or calculate the resistivity of the tissue 30. In some examples, the applied voltage, current, and / or electric field can be selected, determined, and / or allowed based on the measured resistance of the tissue 30. In some examples, the number of pulses of applied voltage can be selected, determined, and / or otherwise used based on the measured resistance of the tissue.

[0062] In some embodiments, sensors for detecting and / or determining the electric field strength, such as gaussmeters and / or teslameters, may also be used. In such embodiments, the sensors may be operatively communicated with controller 14 to ensure that the electric field strength is maintained at the target level for the desired treatment regimen.

[0063] In some embodiments, an ablation device for delivering electrolytic electroporation (e.g., Figure 1The medical device system 40) can be delivered via a computer-aided remote manipulator system, sometimes referred to as a robot-assisted system or a robotic system. The manipulator system includes one or more manipulators that can be operated with the assistance of an electronic controller (e.g., a computer) to move and control the functions of one or more devices when they are coupled to the manipulator. Figure 2 An exemplary embodiment of a robot-assisted manipulator system 100 for use with the systems and methods described herein is shown. The manipulator system can be used, for example, in surgical, diagnostic, therapeutic, biopsy, or non-medical procedures.

[0064] refer to Figure 2 The robot-assisted manipulator system 100 may include one or more manipulator components 102 for operating one or more medical device systems 104 while performing various procedures on a patient P positioned on a table T in a medical environment 101. For example, the manipulator component 102 may drive the movement of a medical device or end effector, apply treatment to target tissue, and / or manipulate control members. The manipulator component 102 may be a remotely operated, non-remotely operated, or hybrid remotely and non-remotely operated component, having selectable degrees of freedom of motion capable of being motorized and / or remotely operated, and selectable degrees of freedom of motion capable of being non-motorized and / or non-remotely operated. An operator input system 106, which may be located inside or outside the medical environment 101, generally includes one or more control devices for controlling the manipulator component 102. The manipulator component 102 supports the medical device system 104 and may optionally include a plurality of actuators or motors that drive inputs on the medical device system 104 in response to commands from the control system 112. The actuator may optionally include a drive system that, when coupled to the medical device system 104, advances the medical device system 104 into a naturally occurring or surgically created anatomical opening. Other drive systems may enable the distal end of the medical device system 104 to move in multiple degrees of freedom, which may include three linear degrees of motion (e.g., linear motion along the X, Y, Z Cartesian axes) and three rotational degrees of motion (e.g., rotation about the X, Y, Z Cartesian axes). The manipulator assembly 102 may support a variety of other systems for irrigation, treatment, or other purposes. Such systems may include fluid systems (including, for example, reservoirs, heating / cooling elements, pumps, and valves), generators, lasers, interrogators, and ablation components.

[0065] The robot-assisted manipulator system 100 also includes a display system 110 for displaying images or representations of the surgical site and medical device system 104 generated by imaging system 109, which may include an imaging system such as an endoscopic imaging system. The display system 110 and operator input system 106 can be configured such that an operator can use telepresent perception to control the medical device system 104 and the operator input system 106. A graphical user interface can be displayed on the display system 110 and / or the display system of a stand-alone planning workstation.

[0066] In some embodiments, the endoscopic imaging system components of imaging system 109 may be integrally or detachably coupled to medical device system 104. However, in some examples, a separate imaging device (such as an endoscope) attached to a separate manipulator assembly may be used in conjunction with medical device system 104 to image surgical sites. Endoscopic imaging system 109 may be implemented as hardware, firmware, software, or a combination thereof, which interact with or are otherwise executed by one or more computer processors—which may include the processor of control system 112.

[0067] The robot-assisted manipulator system 100 may also include a sensor system 108. The sensor system 108 may include an orientation / position sensor system (e.g., an actuator encoder or electromagnetic (EM) sensor system) and / or a shape sensor system (e.g., a fiber optic shape sensor) for determining the orientation, orientation, velocity, rate, attitude, and / or shape of the medical device system 104. The sensor system 108 may also include temperature, pressure, force, or contact sensors, etc.

[0068] The robot-assisted manipulator system 100 may also include a control system 112. The control system 112 includes at least one memory 116 and at least one computer processor 114 for controlling the medical device system 104, the operator input system 106, the sensor system 108, and the display system 110. The control system 112 also includes programming instructions (e.g., a non-transitory machine-readable medium storing the instructions) to implement programs using the robot-assisted manipulator system, including navigation, steering, imaging, deployment or retraction of engagement features, application of treatment to target tissue (e.g., via energy application), etc.

[0069] The control system 112 may optionally further include a virtual visualization system to provide navigational assistance to the operator O when controlling the medical device system 104 during image-guided surgical procedures. Virtual navigation using the virtual visualization system may be based on reference to a preoperative or intraoperative dataset of acquired anatomical access routes. The virtual visualization system processes images of surgical sites imaged using imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), fluorescein imaging, thermography, ultrasound, optical coherence tomography (OCT), thermal imaging, impedance imaging, laser imaging, nanotube X-ray imaging, and / or similar techniques. The control system 112 may use preoperative images to locate target tissue (using visual imaging techniques and / or by receiving user input) and create a preoperative plan, including an optimal first location for performing the treatment. The preoperative plan may include, for example, the planned dimensions for expanding the expandable device, treatment duration, treatment temperature, and / or multiple deployment locations.

[0070] Figure 3A A medical device system 200 according to some exemplary embodiments is illustrated. The medical device system 200 can be used for image-guided medical procedures. In some embodiments, the medical device system 200 can be used for non-remotely operated exploratory procedures or for procedures involving conventionally manually operated medical devices, such as endoscopy. In other embodiments, the medical device system 200 is associated with… Figure 2 The medical device system 104 is interchangeable or a variant thereof.

[0071] Medical device system 200 includes an elongated flexible device 202, such as a flexible catheter, endoscope (e.g., duodenoscope, gastroscope, bronchoscope), or other suitable component coupled to drive unit 204. The elongated flexible device 202 includes a flexible body 216 having a proximal portion 217 and a distal portion 218 including a tip portion. In some embodiments, the flexible body 216 has an outer diameter of approximately 14-20 mm. Other embodiments of the flexible body 216 may have a larger or smaller outer diameter. When the flexible body 216 is inserted into a patient's mouth or nasal cavity, the flexible body 216 may have an appropriate length to reach portions of anatomical structures, such as the lungs, sinuses, larynx, or upper or lower gastrointestinal regions.

[0072] The medical device system 200 optionally includes a tracking system 230 for determining the orientation, velocity, rate, attitude, and / or shape of the distal portion 218 and / or one or more segments 224 along the flexible body 216 using one or more sensors and / or imaging devices. The flexible body 216 can be effectively divided into segments 224 along its entire length between the distal portion 218 and the proximal portion 217. The tracking system 230 can optionally be implemented as hardware, firmware, software, or a combination thereof, with one or more computer processors—including… Figure 2 The processor of the control system 112 in the system—interacts with or otherwise executes by it.

[0073] Tracking system 230 may optionally track one or more of distal portions 218 and / or segments 224 using shape sensor 222. In some embodiments, tracking system 230 may optionally and / or additionally use orientation sensor system 220 (such as an electromagnetic (EM) sensor system) to track distal portion 218. In some examples, orientation sensor system 220 may be configured and positioned to measure six degrees of freedom (e.g., three azimuth coordinates X, Y, and Z and three orientation angles indicating pitch, yaw, and roll of a base point) or five degrees of freedom (e.g., three azimuth coordinates X, Y, and Z and two orientation angles indicating pitch and yaw of a base point).

[0074] The flexible body 216 includes one or more channels (e.g., pathways) that are sized and shaped to receive one or more medical devices 226. In some embodiments, the flexible body 216 includes two channels 221 for a single device 226; however, a different number of channels 221 may be provided. Figure 3BThis is a simplified diagram of an end portion of a flexible body 216 according to some embodiments, from which a medical device 226 extends outward. In some embodiments, the medical device 226 can be used for procedures and aspects thereof, such as surgery, biopsy, ablation, mapping, imaging, illumination, irrigation, or aspiration. The medical device 226 can be deployed through channels 221 of the flexible body 216 and used at a target location within an anatomical structure. The medical device 226 may include, for example, image capturing devices, biopsy instruments, ablation instruments, catheters, laser ablation fibers, and / or other surgical, diagnostic, or therapeutic tools. Medical tools may include end effectors having a single working component such as a scalpel, blunt blade, lens, fiber optic cable, electrode, and / or the like. Other end effectors may include, for example, forceps, clamps, balloons, needles, scissors, clamp applicators, and / or the like. Other end effectors may further include electrically activated end effectors, such as electrosurgical electrodes, transducers, sensors, imaging devices, and / or the like. The medical device 226 can be advanced from the opening of the channel 221 to perform a procedure (e.g., electroporation and / or electrolysis in this disclosure) and then retracted into the channel 221 upon completion of the procedure. The medical device 226 can be removed from the proximal portion 217 of the flexible body 216 or from another optional device port (not shown) along the flexible body 216. The medical device 226 can be used in conjunction with an image capturing device (e.g., an endoscopic camera) also located within the elongated flexible device 202. Alternatively, the medical device 226 itself can be an image capturing device.

[0075] Medical device 226 may additionally accommodate cables, linkages, or other actuation controls (not shown) extending between its proximal portion 217 and distal portion 218, thereby controllably bending the distal portion 218 of medical device 226. Flexible body 216 may also accommodate cables, linkages, or other steering controls (not shown) extending between drive unit 204 and distal portion 218, thereby controllably bending the distal portion 218, as illustrated by dashed line 219 of distal portion 218. In some examples, at least four cables are used to provide independent "up / down" steering to control the pitch motion of distal portion 218, and to provide independent "left / right" steering to control the yaw motion of distal portion 218. In embodiments where medical device system 200 is actuated by a robot-assisted component, drive unit 204 may include a drive input detachably coupled to and receiving power from a drive element (such as an actuator) of a remotely operated component. In some embodiments, the medical device system 200 may include a gripping feature, a manual actuator, or other components for manually controlling the movement of the medical device system 200. Information from the tracking system 230 may be sent to the navigation system 232, where it is combined with information from the visualization system 231 and / or a preoperatively acquired model to provide real-time location information to a physician or other operator.

[0076] In some embodiments, the medical device system 200 can be manually or guided via a robot-assisted manipulator system 100 to deliver the medical device 226 to a target tissue site for treatment. In some procedures, the choice between manual or robotic delivery and the appropriate route can be determined based on the medical application. For example, in some gastrointestinal applications, the medical device system 200 (or the stand-alone medical device 226) can be delivered intracavitarily via a manual or robotic delivery device via an oral or anal route. Transabdominal routes using integrated bipolar instruments, drop-in probes, or catheters can also be used. For urinary applications, the medical device system 200 (or the stand-alone medical device 226) can be delivered intracavitarily via a manual or robotic delivery device via an integrated bipolar instrument, drop-in probe, or catheter, via a transurethral, ​​perineal, preperitoneal, or transabdominal route. Similarly, for gynecological applications, the medical device system 200 (or stand-alone medical device 226) can be delivered intracavitarily via a manual or robotic delivery device using an integrated bipolar device, a drop-in probe, or a catheter, through the vagina, perineum, or abdomen. For hepatobiliary applications, the medical device system 200 (or stand-alone medical device 226) can be delivered intracavitarily via a manual or robotic delivery device using an integrated bipolar device, a drop-in probe, or a catheter, through the mouth to the ampulla of Vater, or through the gastrointestinal wall or abdomen to the liver. For neurovascular applications, the medical device system 200 (or stand-alone medical device 226) can be delivered intravascularly via a manual or robotic delivery device using an integrated bipolar device, a drop-in probe, or a catheter, through a keyhole craniotomy or via an intravascular approach. For cardiac applications, the medical device system 200 (or stand-alone medical device 226) can be delivered via an integrated bipolar device, a drop-in probe, or via a catheter, through an intravascular route or through the thoracic cavity, via a manual or robotic delivery device.

[0077] Common Reference Figures 4-11 The following provides additional details on various embodiments and features related to the design of the electrode therapy system and its various components, which can be compared with previous references. Figures 1-3B The described system 10, robot-assisted manipulator system 100, and / or medical device system 200 are used in combination. Generally, refer to... Figures 4-11 The described electrode therapy system is designed to maintain a compact, low profile overall to facilitate delivery to the target tissue site and retraction after treatment. Further features and advantages of the electrode therapy system design are described below with reference to the accompanying drawings.

[0078] Figures 4-7Together, an electrode therapy system 400 according to an exemplary embodiment is illustrated. The electrode therapy system 400 is operable for delivering a flexible substrate 422 with electrodes 424 to a target tissue region (e.g., Figure 1 (tissue 30). According to exemplary embodiments of the present disclosure, the electrode treatment system 400 can be used to provide electrolytic and / or electroporation treatment to a target tissue region, such as for duodenal mucosal surface reconstruction in the gastrointestinal tract.

[0079] General Reference Figure 4 The electrode treatment system 400 includes an elongated flexible member 402, such as a flexible catheter, endoscope (e.g., duodenoscope, gastroscope, bronchoscope), or other suitable member, having a housing 404 having a proximal portion 406 and a distal portion 408. In some embodiments, the flexible housing 404 has an outer diameter of approximately 8-18 mm. Other embodiments of the flexible housing 404 may include a larger or smaller outer diameter, which may depend on the target anatomical structure being treated (e.g., between 2 mm and 12 mm). When the elongated flexible member 402 is inserted into a patient's mouth or nasal cavity (or otherwise introduced, such as via a surgical incision), the flexible housing 404 may have an appropriate length to reach portions of anatomical structures, such as the lungs, sinuses, larynx, or upper or lower gastrointestinal regions. In some embodiments, the length of the elongated flexible member 402 may range between 85 cm and 300 cm (or have another suitable length) to reach desired anatomical tissue areas for treatment. It should be understood that in other embodiments, the elongated flexible member 402 and its components may have any suitable size, which may depend on the target tissue area, surrounding anatomical structures or other suitable factors.

[0080] Figure 5 This is an enlarged end view of the distal portion 408 of the electrode therapy system 400. See details. Figure 5 The housing 404 includes a first working channel 410, which has an opening on its distal side 412. In some example systems, the first working channel 410 may have a generally elliptical or kidney-shaped profile as shown. In other embodiments, the working channel 410 may have other suitable profiles. Figure 5As shown, the first working channel 410 includes a first seat 414 and a second seat 416 laterally offset from each other, with a ridge or protrusion 418 located between them. As described in further detail below, the first seat 414 and the second seat 416 each receive a wound or coiled portion of the flexible substrate 422. The distal side 412 of the housing 404 may also include a second working channel 420 having a second opening on the distal side 412 of the housing 404, wherein the second working channel 420 is offset from the first working channel 410 on the distal side 412. In some exemplary embodiments, in addition to the working channels for supporting other features of the electrode treatment system 400 (such as imaging devices, sensing devices, illumination devices, suction systems, flushing systems, etc.) specifically described herein, the distal side 412 of the housing 404 may also include any number of working channels (e.g., 421a, 421b, 421c, 421d) having corresponding openings on the distal side 412 of the housing 404.

[0081] The electrode therapy system 400 further includes a flexible substrate 422, which may be a thin layer or sheet made of an electrically insulating polymer material, such as polyimide, polyester, or other suitable thermoplastic or thermosetting polymer film. In other embodiments, the flexible substrate 422 may include a polymer-coated material. The flexible substrate 422 includes electrodes 424 deposited or otherwise supported thereon, wherein the electrodes 424 are adapted to provide one or both of electrolysis and / or electroporation to the target tissue in a manner similar to that described above. Thus, the electrodes 424 may take any suitable configuration operable for generating an electric field. For example, in one embodiment, the electrodes 424 may include multiple metallic traces deposited on the flexible substrate 422. The metallic traces may include any suitable conductive material, such as gold, copper, stainless steel, titanium, graphene, graphite, etc. Generally, electrode materials may be selected such that the electrode material does not actively participate in electrolysis products and / or leave material residues. In some embodiments, the electrode material may be selected to minimize ion transfer from the electrode material to the target tissue. While titanium and gold can participate in the electrolysis process to some extent, they may not generate toxic residues and are therefore preferred in some examples. In other embodiments, electrode 424 may include other suitable electrode shapes and configurations, including circular, square, rectangular, or other shapes. Interdigitated electrodes may also be used. The electrodes disclosed herein may be one, two, or other suitable numbers of electrodes. The electrodes may form an electrode array or be part of an electrode array.

[0082] Generally, the electrodes 424 used in the exemplary configuration described herein are arranged in a bipolar configuration. In a bipolar configuration, current can flow from one electrode in a pair of electrodes to the second electrode in that pair. Therefore, the electrodes in this pair of electrodes can have opposite polarities. In some configurations, multiple pairs of electrodes may be used, with current flowing through each respective electrode pair.

[0083] In other examples, the electrodes of electrode 424 may be arranged in a monopolar configuration or in a combination of a bipolar and monopolar configuration. A monopolar configuration may include an active electrode (e.g., an electrode on or within a surgical area) and a loop electrode. In some examples, the loop electrode may be placed outside the surgical area but in contact with the patient (e.g., using a pad with electrodes). In this way, one polarity (e.g., the polarity of the active electrode) is within the surgical area. Therefore, a monopolar configuration of the electrode may include a pair of electrodes—one energized and one acting as a loop. The loop electrode may not be provided on the same device as the energized electrode. For example, the loop electrode may be provided on a pad near tissue placement. In a monopolar configuration, in some examples, multiple active electrodes may be present and current may flow through a shared loop electrode, or in other examples, multiple separate loop electrodes.

[0084] The electrode therapy system 400 further includes suitable wiring, circuitry, and other electronic components (not shown) for providing electrical signals (such as voltage and / or current) to the electrode 424. In one embodiment, the wiring may travel along the length of the elongated flexible member 402 or otherwise extend to the controller 14 and / or the power supply 12 (see [link to documentation]). Figure 1 The controller 14 and / or power supply 12 may be external. In other embodiments, other suitable wiring configurations may be used to power the electrode 424.

[0085] Back Figure 4 The flexible substrate 422 is coupled to a drive system 428, which is operable to control the deployment and retraction of the flexible substrate 422 (and, by extension, control the deposition or otherwise supported electrodes 424 thereon), as further described below (e.g., common reference). Figures 4-7In one exemplary embodiment, the drive system 428 includes a first drive element 430, such as an elongated flexible drive shaft or other suitable elongated member capable of transmitting mechanical power, torque, and rotation. The first drive element 430 includes a proximal portion 432 and an opposite distal portion 436, the proximal portion 432 being coupled to a driver 434 (e.g., a motor and / or a motor driver), and the distal portion 436 extending into a housing 404 and coupled to a first portion of the flexible substrate 422. The drive system 428 further includes a second drive element 438 having similar or identical features and characteristics to the first drive element 430. The second drive element 438 includes a proximal portion 440 and an opposite distal portion 444, the proximal portion 440 being coupled to a driver 442 (e.g., a motor and / or a motor driver), and the distal portion 444 extending into the housing 404 and coupled to a second portion of the flexible substrate 422 in a similar or identical manner to the first drive element 430. In some embodiments, the drivers 434, 442 may be independently controllable (e.g., via the manipulator assembly 102, operator input system 106, control system 112, or other suitable processing system) to drive the drive elements 430, 438 independently of each other, as described in further detail below (e.g., see specific references). Figure 7 It should be understood that, in other embodiments, drive elements 430, 438 may instead be coupled to and controlled by a single driver (unlike the two separate drivers 434, 442), the single driver being operable to drive drive elements 430, 438 independently or concurrently. In some embodiments, the electrode therapy system 400 and other electrode therapy systems described herein can be manually actuated by a user. In other embodiments, the electrode therapy system may be coupled to an external device, such as a robot-assisted manipulator system (e.g., robot-assisted manipulator system 100), for actuation. In yet another embodiment, both manual and robot-assisted actuation may be provided.

[0086] The electrode therapy systems described herein can be coupled to external devices to provide actuation, control, and / or power to the electrode therapy systems. For example, the electrode therapy system 400 and other electrode therapy systems described herein can be actuated by a robot-assisted manipulator system (e.g., manipulator assembly 102). The electrode therapy system 400 (e.g., elongated flexible member 402, housing 404, and / or one or more drive elements 430, 438) may include or be coupled to a drive unit (e.g., drive unit 204) having one or more drive inputs (e.g., at one or more proximal portions 432, 440) detachably coupled to and receiving power from the drive elements (such as actuators, motors, etc.) of the manipulator assembly 102. When the electrode therapy system 400 is coupled to the manipulator assembly 102, the drive inputs of the electrode therapy system 400 may be coupled to the drive outputs of the manipulator assembly 102 driven by the drive elements of the manipulator assembly 102. Such a driving element of the manipulator assembly 102 may be, or otherwise include, a driver (e.g., driver 434, 442) of the electrode therapy system 400. In such embodiments, the drivers 434, 442 of the electrode therapy system 400 and other electrode therapy systems described herein may be located on, within, or otherwise operatively coupled to the manipulator assembly 102. Furthermore, the drive input of the electrode therapy system 400 may be coupled to the distal portion of the electrode therapy system 400 via one or more actuation drive members or elements (e.g., drive shaft, actuation cable, actuation rod, tension member, etc.) to perform actions such as advancing, retracting, or hinged extension, deployment, and / or retraction of the distal end of the electrode therapy system 400 and the flexible substrate 422 described herein, thereby adjusting the electrode 424 between a therapeutic extension position and a retracted position. In some embodiments, drive elements 430, 438 of the electrode therapy system 400 may be coupled to drive unit 204 for adjusting a flexible substrate (e.g., flexible substrate 422) between an extended position and a retracted position. Furthermore, drive unit 204 may be coupled to a controller (e.g., controller 14) and / or a power source (e.g., power source 12) to provide power to the electrodes of the electrode therapy system 400 described above. Drive unit 204 may be electrically coupled to the electrodes via one or more cables extending along or through the electrode therapy system 400. In alternative embodiments, the controller and power source may supply power to the cables without being coupled to the drive unit (e.g., the controller and power source may be independent of the drive unit).

[0087] As described above, the driving elements 430, 438 are coupled to the flexible substrate 422 and are actuable to deploy the flexible substrate 422 from the housing 404. (See Common Reference) Figure 5 and Figure 6The following provides details of an exemplary coupling arrangement between the flexible substrate 422 and the driving elements 430, 438. See below for further details. Figure 5 The flexible substrate 422 includes a first portion 446 (e.g., a first end of the flexible substrate 422) coupled to a distal portion 436 of a first driving element 430 and a second portion 448 (e.g., a second end of the flexible substrate 422 opposite to the first end) coupled to a distal portion 444 of a second driving element 438. The flexible substrate 422 can be coupled to the driving elements 430, 438 in any suitable manner. For example, in one embodiment, the first driving element 430 and the second driving element 438 may each include channels 450, 452 formed along their respective distal portions 436, 444, wherein the first portion 446 of the flexible substrate 422 extends into the channel 450 of the first driving element 430 and the second portion 448 of the flexible substrate 422 extends into the channel 452 of the second driving element 438. In this configuration, the first portion 446 and the second portion 448 of the flexible substrate 422 can be joined to the respective driving elements 430, 438 in place (e.g., via adhesive or other suitable material). In other embodiments, in addition to extending into the channels 450, 452 of the drive elements 430, 438, or instead of extending into the channels 450, 452 of the drive elements 430, 438, the first portion 446 and the second portion 448 of the flexible substrate 422 may alternatively be partially or completely wound around and coupled in place around the respective distal portions 436, 444 of the drive elements 430, 438. Other embodiments may use other suitable coupling arrangements.

[0088] refer to Figure 5When the flexible substrate 422 is in the retracted position within the housing 404, a first retracted segment 454 of the flexible substrate 422 surrounds the distal portion 436 of the first drive element 430, and a second retracted segment 456 of the flexible substrate 422 surrounds the distal portion 444 of the second drive element 438. Preferably, the first retracted segment 454 and the second retracted segment 456 are wound around the respective first drive element 430 and second drive element 438 in directions opposite to each other to facilitate deployment and retraction and / or removal, as described in further detail below. In this configuration, the unfolded segment 458 of the flexible substrate 422 extends between the first retracted segment 454 and the second retracted segment 456, as shown. In one exemplary embodiment, a first retractable segment 454 of the flexible substrate 422 is received within a first seat 414 of the working channel 410, and a second retractable segment 456 of the flexible substrate 422 is received within a second seat 416 of the working channel 410, wherein the first retractable segment 454 is laterally offset from the second retractable segment 456 within the working channel 410, as shown. As shown, the first retractable segment 454 surrounds the distal portion 436 of the first drive element 430 about a first axis of rotation A. The second retractable segment 456 surrounds the distal portion 444 of the second drive element 438 about a second axis of rotation B, which is spaced apart from or otherwise offset (e.g., parallel) from the first axis of rotation A.

[0089] In some embodiments, the flexible substrate 422 may have a length of approximately 20 mm in its flat and relaxed configuration. In other embodiments, the flexible substrate 422 may have an axial length ranging from 10 to 40 mm. When in the stowed position, the first stowed segment 454 and the second stowed segment 456 may each have a diameter substantially equal to each other. In other embodiments, the diameters of the stowed segments 454 and 456 may differ slightly. In some examples, the diameter of each stowed segment 454 and 456 may be approximately 6 mm wide, and when the two stowed segments 454 and 456 are arranged in the double-wound configuration shown, the flexible substrate 422 measures approximately 12 mm wide overall. In other embodiments, the first stowed segment 454 and the second stowed segment 456 may each have a diameter ranging from approximately 2 mm to 12 mm.

[0090] In some embodiments, the electrode therapy system 400 may further include a sheath 460 disposed within a housing 404, wherein the sheath 460 supports the flexible substrate 422. In an exemplary embodiment, the sheath 460 may be coupled to a working channel 410 or may be formed as an integral part of the working channel 410, such that the sheath 460 is operatively in communication with the working channel 410. In such embodiments, the sheath 460 may include a first seat and a second seat (e.g., seats 414, 416), on which the flexible substrate 422 is received, wherein these seats of the sheath 460, in addition to having similar features and functions as described above. In some embodiments, when the flexible substrate 422 is in a retracted position within the housing 404, the sheath 460 further assists in holding the flexible substrate 422 in its retracted configuration relative to the drive elements 430, 438. Figure 6 As shown, the sheath 460 may have a generally elliptical profile that matches the profile of the flexible substrate 422 when it is in the retracted position, wherein the flexible substrate 422 is securely received within the sheath 460 and held therein in place until deployment.

[0091] General Reference Figures 4-7 The following describes an exemplary delivery procedure of the electrode therapy system 400 to a target tissue site according to an exemplary embodiment, as well as an exemplary deployment of the flexible substrate 422 and the electrode 424. In one example, the electrode therapy system 400 (e.g., an endoscope) may be delivered orally to the duodenum for ablation of the mucosal lining (or other tissue sites). For this procedure, delivery may include entry through the patient's esophagus, navigation through the stomach, and ultimately into the duodenum for treatment. As the electrode therapy system 400 is positioned appropriately in the duodenum, actuators 434, 442 cause corresponding drive elements 430, 438 to move axially (e.g., translate) relative to the housing 404, and drive the first retractable section 454 and the second retractable section 456 of the flexible substrate 422 outwardly from the distal side 412 of the housing 404, respectively, through the opening of the working channel 410. In embodiments of the electrode therapy system 400 that include a sheath 460 coupled to (or integrally formed with) the working channel 410, drive elements 430, 438 are axially moved through the sheath 460 and toward the distal side of the housing 404 in a manner similar to that described.

[0092] For details, please refer to the following: Figure 7The drive elements 430, 438 are axially moved through the working channel 410 until the flexible substrate 422 exits the distal side 412 of the housing 404 (e.g., distally spaced from the distal side 412) to accommodate deployment. In some embodiments, the flexible substrate 422 is spaced approximately 2 mm to 100 mm from the distal side 412 of the housing 404. In some embodiments, the flexible substrate 422 may be spaced sufficiently from the distal side 412 of the housing 404 to allow visualization of the flexible substrate 422 by an imaging system, camera, or other suitable imaging device of the electrode treatment system 400 that may have a field of view extending through another working channel (e.g., working channel 420). Visualization of the flexible substrate 422 can help ensure that the electrode 424 is correctly positioned relative to the treated tissue and can also help facilitate the retraction of the flexible substrate 422, such as ensuring that the tissue is not clamped or stuck by any component of the electrode treatment system 400 during retraction.

[0093] like Figure 7 As shown, once the flexible substrate 422 is positioned distal to the housing 404 and in the appropriate location at the target tissue site, the first retractable section 454 and the second retractable section 456 can be deployed to deploy the flexible substrate 422 and position the electrode 424 against the tissue 462 for treatment. In one embodiment, the first drive element 430 and the second drive element 438 can be rotated in opposite directions relative to each other via the drive system 428 (e.g., about respective axes A and B) to deploy the first retractable section 454 from the first drive element 430 and the second retractable section 456 from the second drive element 438, respectively. In some embodiments, the drive elements 430 and 438 can be actuated simultaneously to ensure substantially symmetrical deployment of the flexible substrate 422. As described above, the first retractable section 454 and the second retractable section 456 are wound relative to each other in opposite directions, such that the opposite rotation of the drive elements 430 and 438 moves the flexible substrate 422 from the retracted position (shown in…) Figure 5 Deploy to extended locations (see) Figure 7 ).

[0094] In some embodiments, the top and bottom surfaces of the flexible substrate 422 may be coated with a suitable polymeric material (or may be made of such a material) to reduce friction from the overlapping portions of the flexible substrate 422 when in the retracted position, thereby facilitating deployment via the drive elements 430, 438. A protective coating may also cover some or all of the electrodes 424 disposed on the flexible substrate 422. In these embodiments, the protective coating may comprise silicone, parylene, or other suitable coatings. Silicone and parylene can both act as suitable insulators to minimize potential complexity in the event of improper electrode deployment. In some embodiments, the internal lubricity created by the protective coating can facilitate smooth deployment and deployment of the flexible substrate 422 because it can reduce friction between the overlapping portions of the flexible substrate 422, especially where the materials constituting the flexible substrate 422 may be somewhat sticky or tacky. Furthermore, the protective coating can help prevent the electrodes 424 from sticking to tissue and / or themselves when retracting from the deployed configuration to the retracted configuration for removal.

[0095] Preferably, the drive elements 430, 438 are rotated in opposite directions until the flexible substrate 422 is deployed and the electrode 424 is correctly positioned relative to the tissue 462. In some embodiments, the electrode 424 may contact the tissue 462, while in other embodiments, the electrode 424 may be adjacent to the tissue 462 but not in contact. In the fully extended position, in some embodiments, the flexible substrate 422 may have an outer diameter of approximately 32 mm. In other embodiments, the flexible substrate 422 in the fully extended position may have an outer diameter ranging from approximately 8 mm to 45 mm. In some embodiments, an imaging system, sensor system, or other suitable visualization system (not shown) of the electrode treatment system 400 may be used to verify that the flexible substrate 422 has extended as desired and that the electrode 424 is correctly positioned.

[0096] Once the flexible substrate 422 is in the extended position, the electrode 424 can be energized to ablate target cells within the tissue 462, as described above. Once the ablation treatment at the tissue site is complete, the drive elements 430, 438 can be rotated in the opposite direction to cause the coiling sections 454, 456 to be wound in an overlapping manner onto the corresponding drive elements 430, 438, for retracting the flexible substrate 422 from the extended position back to the retracted position. Once the flexible substrate 422 is wound into two coiling sections 454, 456 and enters the retracted position, the drive elements 430, 438 are driven or axially translated proximally back into the housing 404 and through the working channel 410 to arrange the flexible substrate 422 back into the retracted position, wherein the first coiling section 454 is received within the first housing 414 and the second coiling section 456 is received within the second housing 416.

[0097] In some embodiments, the counter-rotation of drive elements 430, 438 allows electrode 424 to be deployed and retracted without applying torque to target tissue. Therefore, the electrode therapy system 400 described herein is designed to allow tissue to remain in a neutral position during delivery, treatment, and retraction of the electrode therapy system 400.

[0098] In some embodiments, when the flexible substrate 422 has been moved distally relative to the housing 404, the drive elements 430, 438 can be further actuated via actuators 434, 442, respectively, to adjust the lateral position of the flexible substrate 422. For example, in some embodiments, the flexible substrate 422 may be off-center relative to the cavity of the tissue 462, such that when the flexible substrate 422 is deployed, the electrode 424 may not properly reach all the target tissue. Therefore, the drive elements 430, 438 can be used to adjust the lateral position of the flexible substrate 422 before and / or after deployment to substantially recenter or otherwise position the flexible substrate 422, thereby ensuring that the electrode 424 is correctly positioned after deployment to deliver effective treatment. For example, one drive element can be driven to rotate and / or counter-rotate more than the other drive element, thereby adjusting the lateral position of the flexible substrate 422 and therefore the electrode 424 accordingly.

[0099] As mentioned above Figures 4-7 As described in the illustrated embodiment, the drive system 428 may include individual drivers 434, 442 for independently actuating the drive elements 430, 438. Therefore, in some embodiments, the drive elements 430, 438 may move independently and / or in a coordinated manner to simultaneously deploy the flexible substrate 422, as described above. In other embodiments, the drive elements 430, 438 may be driven completely independently, but not in a coordinated manner, such that the deployment rate and / or deployment amount of the first folding segment 454 may differ from that of the second folding segment 456 based on independent control of the drive elements 430, 438. The ability to independently control the deployment of the folding segments 454, 456 can be beneficial in ensuring that the flexible substrate 422 is deployed as needed according to the given characteristics and features of the target tissue site.

[0100] In yet another embodiment, the electrode therapy system 400 may be configured in a manner generally similar to that described above, but the flexible substrate 422 may be deployed and retracted solely by rotation of one of the drive elements 430, 438. For example, the electrode therapy system 400 may include a first drive element 430 and a second drive element 438, which are configured in accordance with the above reference. Figures 4-7The flexible substrate 422 is coupled in a similar manner as described. In one exemplary embodiment, the actuator 434 is operable to rotate the first drive element 430 about a rotation axis, while the second drive element 438 is non-rotatable relative to the first drive element 430 (and vice versa). In this embodiment, the actuators 434, 442 are operable to move the drive elements 430, 438 axially toward the distal side of the housing 404, wherein rotation of the first drive element 430 about the rotation axis both unfolds the first retractable section 454 from the first drive element 430 and unfolds the second retractable section 456 from the second drive element 438 to deploy the flexible substrate 422 from a retracted position to an extended position. Since the second drive element 438 is non-rotatable in this configuration and supports the second retractable section 456, in some embodiments, rotation of the first drive element 430 may cause the first retractable section 454 to unfold (partially or fully) before the second retractable section 456 unfolds. In some embodiments, the actuator 434 is operable to rotate the first drive element 430 about a rotation axis in a first rotational direction to deploy the flexible substrate 422 from a retracted position to an extended position, as described above. Once treatment is complete, the actuator 434 is further operable to rotate the first drive element 430 in a second rotational direction opposite to the first rotational direction to retract the flexible substrate 422 from the extended position back to the retracted position. Thereafter, the actuators 434, 442 axially retract the drive elements 430, 438 to return the flexible substrate 422 to the housing 404.

[0101] Although not explicitly described herein, it should be understood that many of the same features and characteristics of the electrode therapy system 400 using independently actuable drive elements 430, 438 described above are equally applicable to the configuration of the electrode therapy system 400 described in the preceding paragraphs, wherein only one of the drive elements 430, 438 is rotatable, while the other is non-rotatable or otherwise rotatably fixed. Therefore, to avoid repetition, those features will not be further described herein, where it is understood that the embodiments can be combined in suitable ways.

[0102] For reference Figures 4-7As described, arranging the flexible substrate 422 in a double-wound configuration including retractable sections 454, 456 reduces the overall profile of the rolled-up flexible substrate 422 when in the retracted position, compared to a configuration using a single wound flexible substrate around a single axis. Furthermore, this compact design of the flexible substrate 422 is achieved while maintaining an overall size of the flexible substrate 422 in the extended position large enough to support a suitable electrode 424 for the therapeutic purposes described above. In some embodiments, the outer diameter of the flexible substrate 422 in the extended position can range between 3:1 and 6:1 compared to the corresponding outer diameter of each of the first retractable section 454 and the second retractable section 466 when the flexible substrate 422 is in the retracted position. This design allows the flexible substrate 422 to be packaged within a typical duodenoscope or other suitable instrument without sacrificing other typical features and functions of a duodenoscope, such as camera, illumination, suction, irrigation, etc.

[0103] In some embodiments, the electrode therapy system 400 may further include a support structure 464 for the housing 404 and the working channel 410, such as Figure 8 As shown. In some embodiments, the support structure 464 can support as follows: Figures 4-7 The flexible substrate 422, sheath 460, and distal portions 436 and 444 of the drive elements 430 and 438 are arranged in a similar manner as shown. The support structure 464 can also provide additional rigidity along the distal portion 408 of the elongated flexible member 402.

[0104] Figure 9 Another example of an electrode therapy system 900 for delivering a flexible substrate 908 having electrodes (not shown) to a target area is shown. The electrode therapy system 900 includes a gear system 912 for controlling the operation of drive elements 902, 904 coupled to the flexible substrate 908. Generally, the electrode therapy system 900 can have the same characteristics as described in the preceding references. Figures 4-7 The electrode therapy system 400 described has the same or substantially similar features. Therefore, certain details of the electrode therapy system 900 may not be described in further detail below to avoid repeating and / or obscuring more relevant details of this embodiment. In short, refer to... Figure 9 The electrode therapy system 900 includes a first drive element 902 and a second drive element 904 extending into a housing 906, wherein the drive elements 902, 904 are coupled to a flexible substrate 908 and are actuable via a drive system 910 to deploy the flexible substrate 908 in a manner substantially similar to that described above with respect to the electrode therapy system 400. Additional details of features integrated with the electrode therapy system 900, particularly the gear system 912, are provided below.

[0105] refer to Figure 9In some embodiments, the electrode therapy system 900 includes a gear system 912 coupling a first drive element 902 and a second drive element 904 to each other. The gear system 912 essentially allows one of the drive elements 902, 904 to be rotated by a driven system 910, wherein the gear system 912 functions to rotate or otherwise actuate the other drive element 902, 904. For example, in one embodiment, the drive system 910 can rotate the first drive element 902 about a first axis of rotation, and the gear system 912 can further rotate the second drive element 904 about a second axis of rotation spaced apart from the first axis of rotation. (Refer to the foregoing) Figure 4 In a similar manner, via gear system 912, the first drive element 902 can rotate in a first direction and the second drive element 904 can rotate in the opposite second direction, such that drive elements 902 and 904 rotate in opposite directions relative to each other. (See previous reference...) Figure 4 As described, the reverse rotation of drive elements 902 and 904 adjusts the flexible substrate 908 from the retracted position to the treatment extended position. Subsequently, upon completion of treatment retraction and removal, drive elements 902 and 904 can be reversed to adjust the flexible substrate 908 from the extended position to the retracted position.

[0106] Figure 10 Another example of an electrode therapy system 1000 for delivering a flexible substrate 1008 having electrodes 1012 to a target region is shown. Generally, the electrode therapy system 1000 can have the same characteristics as described in the preceding references. Figures 4-7 The electrode therapy system 400 described has the same or substantially similar features. Therefore, certain details of the electrode therapy system 1000 may not be described in further detail below to avoid repeating and / or obscuring more relevant details of this embodiment. In short, refer to... Figure 10 The electrode therapy system 1000 includes a first drive element 1002 and a second drive element 1004 extending into a housing 1006, wherein the drive elements 1002, 1004 are coupled to a flexible substrate 1008 and can be actuated via a drive system 1010 to deploy the flexible substrate 1008 in a manner similar to that described above with respect to the electrode therapy system 400.

[0107] refer to Figure 10 The flexible substrate 1008 can be referenced in the previous text. Figure 4 The similar dual-wound configurations described are coupled to drive elements 1002 and 1004. For example... Figure 10As shown, in some embodiments, the flexible substrate 1008 may include a plurality of longitudinally spaced segments 1008a, 1008b, 1008c, wherein the plurality of segments 1008a, 1008b, 1008c may work together as components of a single larger flexible substrate 1008, or may be independent flexible substrates designed to be energized and controlled independently of each other. Therefore, in some embodiments, segments 1008a, 1008b, 1008c may each include wiring, circuitry, and other electronics (not shown), arranged to power electrodes 1012 supported thereon independently of each other. In other embodiments, segments 1008a, 1008b, 1008c may include shared wiring, circuitry, and other electronics (not shown) and may be electrically coupled to each other and essentially operate in series as a multi-segment flexible substrate 1008. In any configuration, the electrode treatment system 1000 is designed to simplify treatment by increasing the overall area of ​​tissue that can be treated with a single deployment of the flexible substrate 1008, thereby reducing overall treatment time and minimizing potential tissue damage that may occur when the electrode treatment system 1000 is repositioned for subsequent treatment. For example, as Figure 10 As shown, segments 1008a, 1008b, and 1008c are deployed against tissue cavity 1014 to jointly treat tissue regions, which can be approximately three times larger than using a single flexible substrate 1008 (see, for example, see...). Figure 7 ).

[0108] In one embodiment, each segment 1008a, 1008b, 1008c of the flexible substrate 1008 can be referenced above. Figures 4-7 The flexible substrate 1008 is rolled up into three pairs of retractable sections (not shown) in a similar manner as described above. In this configuration, one set of retractable sections from each of the three pairs can be coupled to a first drive element 1002, and a second set of retractable sections from each of the three pairs can be coupled to a second drive element 1004, wherein drive elements 1002, 1004 are operable to deploy and retract the flexible substrate 1008 in a manner similar to that described above. The three pairs of retractable sections can be housed within a sheath 1016 disposed within the housing 1006 to maintain their rolled-up configuration when in the retracted position.

[0109] Figure 11 Another example of an electrode therapy system 1100 for delivering a flexible substrate 1108 having electrodes 1110 to a target area for treatment is shown. Generally, the electrode therapy system 1100 can have the same characteristics as described in the preceding references. Figures 4-7 The electrode therapy system 400 described has the same or substantially similar features. Therefore, certain details of the electrode therapy system 1100 may not be described in further detail below to avoid repeating and / or obscuring more relevant details of this embodiment. In short, refer to... Figure 11The electrode therapy system 1100 includes a first drive element 1102 and a second drive element 1104 extending into a housing 1106, wherein the drive elements 1102, 1104 are coupled to a flexible substrate 1108 having electrodes 1100 and can be actuated via a drive system 1112 to deploy the flexible substrate 1108 in a manner similar to that described above with respect to the electrode therapy system 400.

[0110] refer to Figure 11 In some embodiments, the electrode treatment system 1100 further includes an extension member 1114 coupled to an elongated flexible member 1116, wherein the extension member 1114 is radially expandable relative to the elongated flexible member 1116. The extension member 1114 can be expanded in various different ways. For example, in some embodiments, the extension member 1114 can be expanded with a fluid (such as air, saline, radiopaque solution, etc.). In some embodiments, fluid can be introduced into the extension member 1114 through a cavity (not shown) in the elongated flexible member 1116. The extension member 1114 may have a length of approximately 4 cm in its unexpanded configuration and can expand to a diameter of 1 cm to 4 cm. In other embodiments, the length and expandable diameter of the extension member 1114 can vary depending on the characteristics and size of the target site for tissue treatment. In other embodiments, the extension member 1114 can be expanded in other suitable ways (e.g., rolling, unfolding, pushing). In the illustrated embodiment, the extension member 1114 is shown as an expandable balloon. In some embodiments, the balloon may be a compliant balloon made of polyurethane, silicone, or other suitable materials designed to expand several times its nominal size. In other embodiments, the balloon may be a semi-compliant balloon made of polyurethane or other suitable materials designed to expand less than a compliant balloon. In other embodiments, other expansion components, such as woven mesh, expandable frames, etc., may be used.

[0111] In some embodiments, the extension member 1114 may be housed within the housing 1106 and configured to extend through a first working channel 1118, which extends through an elongated flexible member 1116 and has an opening on the distal side 1120 of the housing 1106. In this embodiment, the flexible substrate 1108 may be arranged in a double-wound configuration as described above, wherein the flexible substrate 1108 is disposed within a second working channel 1122, which has an opening on the distal side 1120 of the housing 1106, wherein the first working channel 1118 and the second working channel 1122 are offset from each other on the distal side 1120. For example, in one embodiment, the first working channel 1118 may be vertically offset from (e.g., positioned above) the second working channel 1122. In some embodiments, the working channels 1118, 1122 may be aligned along a vertical axis extending through the distal side 1120 of the housing 1106.

[0112] In this configuration, the extension member 1114 is axially movable relative to the housing 1106 and extends distally thereto via the first working channel 1118 to engage the flexible substrate 1108 after it has been extended to the first extended position via rotation of one or both of the drive elements 1102 and 1104, in a manner similar to that described above. Figures 4-10 The manner described in any embodiment is similar. Once the flexible substrate 1108 is in the first extended position, the extension member 1114 extends distally through the first working channel 1118 and subsequently extends radially to further extend the flexible substrate 1108 from the first extended position to a second extended position. The extension of the extension member 1114 applies a radial force to the flexible substrate 1108, which causes the flexible substrate 1108 to further unfold and / or extend to a second extended position toward the tissue 1124 at the treatment site. As the flexible substrate 1108 is deployed to the second extended position, the electrode 1110 is moved to a position adjacent to (or in contact with) the tissue 1124. In some embodiments, the rate and / or extent of extension of the extension member 1114 can be controlled to ensure that the electrode 1110 properly contacts (or otherwise positions sufficiently close to) the tissue 1124 for treatment, while avoiding over-extension of the flexible substrate 1108, which could lead to tissue damage. With electrode 1110 in the appropriate position, current can flow through electrode 1110 to generate an electric field for electroporation and / or electrolysis, as described above regarding tissue ablation. After treatment is completed, the extension member 1114 can be collapsed and retracted into the first working channel 1118. Subsequently, the flexible substrate 1108 can be retracted to a stowed position via rotation of one or both of the drive elements 1102 and 1104 to remove electrode 1110 from tissue 1124 and facilitate removal of the electrode treatment system 1100.

[0113] As described, the extension member 1114 can support the flexible substrate 1108 to ensure that it is fully deployed and / or extended as needed, so that the electrode 1110 is in a feasible position for therapeutic purposes. Therefore, the flexible substrate 1108 can be deployed to a first extended position via rotation of the drive elements 1102, 1104 as described, and the extension member 1114 can cause the flexible substrate 1108 to extend to a subsequent second extended position, such that the outer diameter of the flexible substrate 1108 in the second extended position is larger than that in the first extended position, thereby ensuring that the electrode 1110 is in the correct position against (or adjacent to) the tissue 1124 for therapeutic purposes.

[0114] As previously described, in some embodiments, the electrode treatment system 1100 can be repositioned (e.g., advanced or retracted relative to a first tissue treatment site) to different areas and the process can be repeated as needed to sequentially treat larger tissue areas. In some embodiments, the flexible substrate 1108 and the extension member 1114 can be readjusted to a fully deployed configuration (e.g., Figure 11 The second tissue treatment site (shown) is used to expedite treatment. In other embodiments, the extension member 1114 may instead be partially or completely deflated, and the flexible substrate 1108 may also be partially or completely retracted to move the electrode treatment system 1100 to the second tissue treatment site. Retracting one or both of these components before moving the electrode treatment system 1100 can facilitate repositioning of the electrode treatment system 1100 by reducing the overall profile of the electrode treatment system 1100, and can also reduce the risk of accidental damage to any surrounding tissue caused by the electrode treatment system 1100 during movement.

[0115] It should be understood that the exemplary embodiments of the catheter delivery system design and its associated potential clinical applications described herein are not intended to be limiting. Many other configurations of the delivery system and applications that would benefit from the use of the disclosed subject matter exist. Furthermore, it should be understood that any of the above embodiments or processes, or specific features associated therewith, according to the system, apparatus, and method, can be combined with one or more other embodiments and / or processes, or can be performed separately and / or between individual devices or device parts.

[0116] Finally, this disclosure is intended to be illustrative of the apparatus, device, system, and method only, and should not be construed as limiting the appended claims to any particular embodiment or group of embodiments. Therefore, while this disclosure has been described in particular detail with reference to exemplary embodiments, it should be understood that various modifications and alternative embodiments may be implemented without departing from the broader spirit and scope of the disclosure as set forth in the appended claims. Accordingly, the specification and drawings are to be viewed in an illustrative manner and are not intended to limit the scope of the appended claims.

Claims

1. An electrode therapy system, the system comprising: shell; A first drive element and a second drive element, each having a proximal portion and an opposite distal portion, wherein the distal portion of each drive element extends into the housing; and A flexible substrate includes electrodes disposed thereon, the flexible substrate having a first portion coupled to the distal portion of a first driving element and a second portion coupled to the distal portion of a second driving element, wherein when the flexible substrate is in a retracted position, a first retracted segment of the flexible substrate surrounds the distal portion of the first driving element and a second retracted segment of the flexible substrate surrounds the distal portion of the second driving element, the first retracted segment and the second retracted segment being laterally offset from each other within the housing.

2. The system of claim 1, wherein the counter-rotation of the first drive element and the second drive element relative to each other unfolds the first folding section from the first drive element and the second folding section from the second drive element to deploy the flexible substrate from the folded position to the extended position.

3. The system of claim 1, wherein the first gathering segment and the second gathering segment are wound around the respective first drive element and the second drive element in opposite directions relative to each other.

4. The system of claim 1, wherein the housing further includes a working channel having an opening on a distal side of the housing, the working channel including a first seat for receiving a first retracted section of the flexible substrate when the flexible substrate is in the retracted position and a second seat for receiving a second retracted section of the flexible substrate.

5. The system of claim 1, wherein the housing further includes a working channel having an opening on the distal side of the housing, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first retractable section and the second retractable section respectively through the opening of the working channel and toward the distal side of the housing.

6. The system of claim 5, wherein when the first collapsing section and the second collapsing section are positioned at the distal side of the housing, the first driving element and the second driving element are actuated to deploy the flexible substrate from the collapsed position to the extended position.

7. The system of claim 1, further comprising a sheath disposed within the housing, the sheath including a first seat for receiving a first retracted section of the flexible substrate when the flexible substrate is in the retracted position and a second seat for receiving a second retracted section of the flexible substrate.

8. The system of claim 7, wherein the housing further includes a working channel having an opening on a distal side of the housing, and wherein the sheath is coupled to the working channel.

9. The system of claim 8, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first retractable section and the second retractable section respectively through the openings of the sheath and the working channel and toward the distal side of the housing.

10. The system of claim 9, wherein when the first collapsing section and the second collapsing section are positioned at the distal side of the housing, the first driving element and the second driving element are actuated to deploy the flexible substrate from the collapsed position to the extended position.

11. The system of claim 1, wherein the first driving element and the second driving element are independently actuable such that, between the retracted position and the extended position, the first driving element drives the first retracted section of the flexible substrate and the second driving element drives the second retracted section of the flexible substrate independently.

12. The system of claim 11, wherein the first drive element is coupled to a first drive system and the second drive element is coupled to a second drive system, and wherein the first drive system and the second drive system are operable independently of each other.

13. The system according to claim 1, further comprising: A drive system coupled to one of the first drive element and the second drive element, the drive system being operable to rotate the one of the first drive element and the second drive element in a first direction; and A gear system that couples the first drive element and the second drive element to each other, wherein the gear system causes the other of the first drive element and the second drive element to rotate in a second direction opposite to the first direction.

14. The system of claim 1, wherein the outer diameter of the flexible substrate in the extended position is between 3:1 and 6:1 compared to the corresponding outer diameter of each of the first and second retracted sections when the flexible substrate is in the retracted position.

15. The system of claim 1, wherein the first driving element and the second driving element are further rotatable to retract the flexible substrate from the extended position back to the retracted position.

16. The system of claim 1, wherein when the flexible substrate is in the retracted position, a segment of the flexible substrate extends between the first retracted segment and the second retracted segment.

17. An electrode therapy system, the system comprising: shell; A first drive element, rotatable about a rotation axis, includes a proximal portion and an opposite distal portion, wherein the distal portion extends into the housing; The second drive element includes a proximal portion and a distal portion, wherein the distal portion extends into the housing; and A flexible substrate includes electrodes disposed thereon, the flexible substrate having a first portion coupled to the distal portion of a first driving element and a second portion coupled to the distal portion of a second driving element, wherein when the flexible substrate is in a retracted position, a first retracted segment of the flexible substrate surrounds the distal portion of the first driving element and a second retracted segment of the flexible substrate surrounds the distal portion of the second driving element, the first retracted segment and the second retracted segment being laterally offset from each other within the housing, and wherein rotation of the first driving element about the rotation axis both unfolds the first retracted segment from the first driving element and unfolds the second retracted segment from the second driving element to deploy the flexible substrate from the retracted position to the extended position.

18. The system of claim 17, wherein the second drive element is not rotatable relative to the first drive element.

19. The system of claim 17, wherein the first driving element is coupled to a driving system operable to rotate the first driving element about the rotation axis in a first rotational direction to deploy the flexible substrate from the retracted position to the extended position.

20. The system of claim 19, wherein the drive system is further operable to rotate the first drive element about the rotation axis in a second rotation direction opposite to the first rotation direction to retract the flexible substrate from the extended position back to the retracted position.

21. The system of claim 17, wherein when the flexible substrate is in the retracted position, a segment of the flexible substrate extends between the first retracted segment and the second retracted segment.

22. The system of claim 17, wherein the first gathering segment and the second gathering segment are wound around the respective first drive element and the second drive element in opposite directions relative to each other.

23. The system of claim 17, wherein the housing further includes a working channel having an opening on a distal side of the housing, the working channel including a first seat for receiving a first retracted segment of the flexible substrate when the flexible substrate is in the retracted position and a second seat for receiving a second retracted segment of the flexible substrate.

24. The system of claim 17, wherein the housing further includes a working channel having an opening on a distal side of the housing, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first retractable section and the second retractable section, respectively, through the opening of the working channel and toward the distal side of the housing.

25. The system of claim 24, wherein when the first collapsing section and the second collapsing section are positioned distal to the housing, the first drive element is actuated to deploy both the first collapsing section and the second collapsing section of the flexible substrate from the collapsed position to the extended position.

26. The system of claim 17, further comprising a sheath disposed within the housing, the sheath including a first seat for receiving a first retracted section of the flexible substrate when the flexible substrate is in the retracted position and a second seat for receiving a second retracted section of the flexible substrate.

27. The system of claim 26, wherein the housing further includes a working channel having an opening on a distal side of the housing, and wherein the sheath is coupled to the working channel.

28. The system of claim 27, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first retractable section and the second retractable section respectively through the openings of the sheath and the working channel and toward the distal side of the housing.

29. The system of claim 28, wherein when the first collapsing section and the second collapsing section are positioned at the distal side of the housing, the first drive element is actuated to deploy both the first collapsing section and the second collapsing section of the flexible substrate from the retracted position to the extended position.

30. The system of claim 17, wherein the outer diameter of the flexible substrate in the extended position is between 3:1 and 6:1 compared to the respective outer diameter of each of the first and second retracted sections when the flexible substrate is in the retracted position.

31. The system of claim 17, wherein the housing further includes a first working channel having a first opening on a distal side of the housing, and the system further includes an extension member capable of extending distally to the housing, along its distal side, and through the first opening of the first working channel, wherein the extension member engages the flexible substrate in the extended position, wherein the extension member is capable of radially extending to further extend the flexible substrate from the extended position to a second extended position.

32. The system of claim 31, wherein the housing further includes a second working channel having a second opening on the distal side of the housing, the second opening being offset from the first opening of the first working channel, wherein the first driving element and the second driving element are axially movable relative to the housing to drive the first retractable section and the second retractable section respectively through the second opening of the second working channel and toward the distal side of the housing.

33. An electrode therapy system, the system comprising: shell; A first drive element and a second drive element, each having a proximal portion and an opposite distal portion, wherein the distal portion of each drive element extends into the housing; and A flexible substrate includes electrodes disposed thereon, the flexible substrate having a first portion coupled to the distal portion of a first driving element and a second portion coupled to the distal portion of a second driving element, wherein when the flexible substrate is in a retracted position, a first retracted segment of the flexible substrate surrounds the distal portion of the first driving element and a second retracted segment of the flexible substrate surrounds the distal portion of the second driving element, the first retracted segment and the second retracted segment are laterally offset from each other within the housing, and wherein rotation of one or both of the first driving element and the second driving element unfolds the first retracted segment from the first driving element and unfolds the second retracted segment from the second driving element to deploy the flexible substrate from the retracted position to a first extended position; and An extension member, which engages the flexible substrate when in the first extended position, wherein the extension member is capable of radially extending to further extend the flexible substrate from the first extended position to a second extended position.

34. The system of claim 33, wherein the housing includes a first working channel having a first opening on a distal side of the housing, wherein the extension member is axially movable relative to the housing and is capable of extending distally thereto through the first opening of the first working channel.

35. The system of claim 34, wherein the housing further includes a second working channel having a second opening on the distal side of the housing, wherein the first driving element and the second driving element are axially movable relative to the housing to drive the first retractable section and the second retractable section respectively through the second opening of the second working channel and toward the distal side of the housing.

36. The system of claim 35, wherein the first opening of the first working channel is offset from the second opening of the second working channel along the distal side of the housing.

37. The system of claim 33, wherein the housing further includes a working channel having an opening on a distal side of the housing, the working channel including a first seat for receiving a first retracted section of the flexible substrate when the flexible substrate is in the retracted position and a second seat for receiving a second retracted section of the flexible substrate.

38. The system of claim 33, further comprising a sheath disposed within the housing, the sheath including a first seat for receiving a first retracted section of the flexible substrate when the flexible substrate is in the retracted position and a second seat for receiving a second retracted section of the flexible substrate.

39. The system of claim 38, wherein the housing further includes a working channel having an opening on a distal side of the housing, and wherein the sheath is coupled to the working channel.

40. The system of claim 39, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first retractable section and the second retractable section respectively through the openings of the sheath and the working channel toward the distal side of the housing.

41. The system of claim 33, wherein the reverse rotation of the first drive element relative to the second drive element simultaneously unfolds the first folding section from the first drive element and the second folding section from the second drive element.

42. The system of claim 41, wherein the first gathering segment and the second gathering segment are wound around the respective first drive element and the second drive element in opposite directions.

43. The system of claim 33, wherein the first driving element and the second driving element are independently actuable such that, between the retracted position and the first extended position, the first driving element drives the first retracted section of the flexible substrate and the second driving element drives the second retracted section of the flexible substrate independently.

44. The system of claim 33, wherein after the flexible substrate is deployed to the second extended position, further rotation of one or both of the first driving element and the second driving element retracts the flexible substrate from the second extended position back to the retracted position.

45. The system of claim 33, further comprising: A drive system coupled to one of the first drive element and the second drive element, the drive system being operable to rotate the one of the first drive element and the second drive element in a first direction; and A gear system that couples the first drive element and the second drive element to each other, wherein the gear system causes the other of the first drive element and the second drive element to rotate in a second direction opposite to the first direction.

46. ​​The system of claim 33, wherein one of the first driving element and the second driving element is not rotatable relative to the other of the first driving element and the second driving element.

47. The system of claim 33, wherein the outer diameter of the flexible substrate in the first extended position is between 3:1 and 6:1 compared to the corresponding outer diameter of each of the first and second retracted sections when the flexible substrate is in the retracted position.

48. The system of claim 47, wherein the outer diameter of the flexible substrate at the second extended position is larger than that at the first extended position.

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