Multi-wrapped electrode treatment systems and methods

Abstract

Apparatuses, systems, and methods are disclosed for providing controlled delivery of electrolysis products and cellular permeabilization treatment to a tissue site. The systems, apparatuses, and methods may include designs with features for efficiently deploying a flexible substrate with an electrode at a tissue site for treatment and for facilitating retraction of the electrode back into a housing after completion of treatment for removal. The systems, apparatuses, and methods may further include an expansion member for radially expanding the flexible substrate to aid in positioning the electrode adjacent the tissue to facilitate treatment.

Description

MULTI-WRAPPED ELECTRODE TREATMENT SYSTEMS AND METHODSCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 63 / 584,669, filed September 22, 2023, which is hereby incorporated by reference in its entirety.TECHNICAL FIELD

[0002] The present disclosure relates generally to the field of tissue treatment. In particular, the disclosure relates to devices and methods with deployable electrodes for ablating cells to treat targeted tissues.BACKGROUND

[0003] Tissues in the body may be treated in surgical or medical procedures using resection and removal. While such procedures may be necessary to treat more extensive damage or resolve various medical conditions, minimally invasive procedures may be used as an alternative in some situations. Such procedures, where applicable, may be preferable to reduce overall patient risk, damage to surrounding tissue, recovery time, discomfort, and potentially harmful side effects as compared to more invasive procedures. In minimally invasive tissue ablation, targeted tissues may be treated inside the body (e.g., in situ) using procedures that do not involve resection or may require minimal resection. 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 aim of these ablation procedures is to destroy abnormal tissue in a targeted region and encourage the regrowth of healthy tissue.

[0004] Another known minimally invasive treatment technique involves electroporation of targeted tissues by localized application of an electrical field to increase permeability of cell membranes, which may then allow drugs or other chemicals to be introduced into the cells for treatment. Electroporation may also be used in combination with electrolysis as a method of tissue ablation, by a process also known as electrolytic electroporation, electroporation-electrolysis, or E2.

[0005] Tissue ablation is a therapeutic procedure used to treat damage to various tissues, including those of the gastrointestinal tract. Damage to intestinal tissue may arise from several sources but is commonly associated with chronic metabolicdisorders such as diabetes. For patients with diabetes, damage to gastrointestinal tissues (particularly the duodenum) may create issues with insulin resistance and / or impair the ability for the body to process glucose. To help manage the disorder, duodenal mucosal resurfacing (DMR) may be used to resurface the patient’s intestinal lining in an effort to help regenerate healthy lining for improving nutrient absorption at the duodenum. Improved health of the intestinal lining may help correct absorption issues and yield a better therapeutic response to insulin for some patients, which in turn may allow patients to replace more aggressive insulin therapies (e.g., injections) with oral medications to help manage the condition.

[0006] Generally, DMR is a procedure that involves introducing a catheter (or other suitable medical instrument system) with an inflatable balloon (or other expansion member) into the duodenum, typically under endoscopic guidance. In one example configuration, the balloon supports a flexible substrate with an electrode disposed thereon, where the electrode is configured for delivering energy to ablate the target tissue region at a controlled depth. Once the catheter is advanced to the target region for treatment, the balloon is inflated to expand the flexible substrate and arrange the electrode adjacent (or in contact with) the tissue. Thereafter, the electrode is energized to ablate the target tissue. Upon completion of treatment at a first tissue site, the catheter may be repositioned to other tissue regions and the ablation process repeated as many times as necessary to treat a large tissue region.

[0007] The inventors have identified a need for an improved electrode treatment system for electroporation and / or electrolysis to ablate cells for treating targeted tissues. Some aspects of the improved electrode treatment system include a flexible substrate wrapped into two separately furled sections to reduce an overall profile of the electrode treatment system for compact delivery to a target tissue site. When deployed, the flexible substrate maintains a sufficiently large surface area to support a suitable electrode for treatment. Additionally, the electrode treatment system may include an expansion member operable to expand the flexible substrate to ensure the electrode is properly positioned relative to the tissue for effective treatment. Other aspects of the improved electrode treatment system include features to independently and / or simultaneously drive each furled section of the flexible substrate to improve overall design flexibility for treatment purposes and to facilitate retraction of the flexible substrate back into a compact, stowed position upon completion of treatment. Additional aspects and advantages of such systems will be apparent from the followingdetailed description of example embodiments, which proceed with reference to the accompanying drawings.SUMMARY

[0008] Various examples of electrode treatment systems for treating tissue are described herein. An example system may include a housing with a first drive element and a second drive element each having a distal portion extending into the housing. The system further includes a flexible substrate with an electrode disposed thereon, 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 stowed position, a first furled section of the flexible substrate encircles the distal portion of the first drive element and a second furled section of the flexible substrate encircles the distal portion of the second drive element. In one example configuration, the first furled section and the second furled section are laterally offset from one another within the housing. In some example systems, counterrotation of the first drive element and the second drive element relative to one another unfurls the first furled section from the first drive element and the second furled section from the second drive element to deploy the flexible substrate from the stowed position to an expanded position for treatment.

[0009] In some example systems, a segment of the flexible substrate extends between the first furled section and the second furled section when the flexible substrate is in the stowed position. In some example systems, the first furled section and the second furled section are wrapped in opposite directions relative to one another around the respective first drive element and the second drive element to facilitate deployment and retraction.

[0010] In some example systems, the housing includes a working channel with an opening on a distal face of the housing, the working channel including a first seat receiving the first furled section of the flexible substrate and a second seat receiving the second furled section of the flexible when the flexible substrate is in the stowed position. In some example systems, the first drive element and the second drive element are axially movable relative to the housing to drive the first furled section and the second furled section, respectively, through the opening of the working channel and distally of the housing. In this configuration, the first drive element and the seconddrive element are actuatable to deploy the flexible substrate from the stowed position to the expanded position.

[0011] In some example systems, the system further includes a sheath disposed within the housing, the sheath including a first seat receiving the first furled section of the flexible substrate and a second seat receiving the second furled section of the flexible substrate when the flexible substrate is in the stowed position. The housing may further include a working channel, where the sheath is coupled to the working channel. In some example systems, the first drive element and the second drive element are axially movable relative to the housing to drive the first furled section and the second furled section, respectively, through the sheath and the opening of the working channel and distally of the housing. The first drive element and the second drive element may be actuatable to deploy the flexible substrate from the stowed position to the expanded position when the first furled section and the second furled section are positioned distally of the housing.

[0012] In some example systems, the first drive element and the second drive element are actuatable independently from one another such that the first drive element drives the first furled section of the flexible substrate and the second drive element drives the second furled section of the flexible substrate independently from one another between the stowed position and the expanded position. The first drive element may be connected to a first drive and the second drive element may be connected to a second drive, wherein the first drive and the second drive are operable independently from one another.

[0013] In some example 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 operable to rotate the 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 one another, wherein the gear system rotates the other of the first drive element and the second drive element in a second direction opposite the first direction.

[0014] In some example systems, the flexible substrate has an outer diameter in the expanded position that ranges between 3:1 and 6:1 as compared to a respective outer diameter of each of the first furled section and the second furled section when the flexible substrate is in the stowed position.

[0015] Another example system may include a housing, a first drive element rotatable about a rotational 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 with an electrode disposed thereon, 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 stowed position, a first furled section of the flexible substrate encircles the distal portion of the first drive element and a second furled section of the flexible substrate encircles the distal portion of the second drive element. In one example configuration, the first furled section and the second furled section are laterally offset from one another within the housing. In some example systems, rotation of the first drive element about the rotational axis unfurls both the first furled section from the first drive element and the second furled section from the second drive element to deploy the flexible substrate from the stowed position into an expanded position. In some example systems, the second drive element is non- rotatable relative to the first drive element.

[0016] In some example systems, the first drive element is coupled to a drive system operable to rotate the first drive element about the rotational axis in a first rotational direction to deploy the flexible substrate from the stowed position into the expanded position. The drive system may be further operable to rotate the first drive element about the rotational axis in a second rotational direction opposite the first rotational direction to retract the flexible substrate from the expanded position to the stowed position.

[0017] In some example systems, the system further includes an expansion member extendable outwardly of the housing along a distal face thereof and through a first opening of the working channel, the expansion member engaging the flexible substrate when in the expanded position, wherein the expansion member is radially expandable to further expand the flexible substrate from the expanded position to a second expanded position. The housing may further include a second working channel with a second opening on the distal face of the housing, the second opening offset from the first opening of the first working channel, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first furled section and the second furled section, respectively, through the second opening of the second working channel and distally of the housing.

[0018] Another example system may include a housing with a first drive element and a second drive element each having a distal portion extending into the housing. The system further includes a flexible substrate with an electrode disposed thereon, 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 stowed position, a first furled section of the flexible substrate encircles the distal portion of the first drive element and a second furled section of the flexible substrate encircles the distal portion of the second drive element. In this configuration, the first furled section and the second furled section laterally offset from one another within the housing. In some example systems rotation of one or both of the first drive element and the second drive element unfurls the first furled section from the first drive element and the second furled section from the second drive element to deploy the flexible substrate from the stowed position into a first expanded position. The system further includes an expansion member engaging the flexible substrate when in the first expanded position, wherein the expansion member is radially expandable to further expand the flexible substrate from the first expanded position to a second expanded position.

[0019] In some example systems, the housing includes a first working channel with a first opening on a distal face of the housing, wherein the expansion member is axially movable relative to the housing and extendable distally thereto through the first opening of the first working channel. The housing may further include a second working channel with a second opening on the distal face of the housing, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first furled section and the second furled section of the flexible substrate, respectively, through the second opening of the second working channel and distally of the housing. The first opening of the first working channel may be offset from the second opening of the second working channel along the distal face of the housing.

[0020] In some example systems, counterrotation of the first drive element relative to the second drive element simultaneously unfurls the first furled section from the first drive element and the second furled section from the second drive element. In some example systems, after deployment of the flexible substrate to the second expanded position, further rotation of the one or both of the first drive element and the seconddrive element retracts the flexible substrate from the second expanded position to the stowed position.

[0021] In some example systems, the flexible substrate has an outer diameter in the first expanded position that ranges between 3:1 and 6:1 as compared to a respective outer diameter of each of the first furled section and the second furled section when the flexible substrate is in the stowed position. Inn some example systems, the outer diameter of the flexible substrate is larger in the second expanded position as compared to the first expanded position.

[0022] It should be understood that the foregoing summary provides various examples further described herein and is not intended to identify any key or critical aspects of the disclosed or claimed subject matter. Further, aspects of the example systems summarized above may be combined in any suitable manner without departing from the principles of the disclosed or claimed subject matter.BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The foregoing and other features of the present disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several examples in accordance with the disclosure and are therefore not to be considered limiting in scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which:

[0024] FIG. 1 is a schematic illustration of a system for electroporation and / or electrolysis in accordance with examples described herein.

[0025] FIG. 2 is a schematic illustration of a robotically-assisted manipulator system in accordance with examples described herein.

[0026] FIG. 3A is a schematic diagram of a medical instrument system in accordance with examples described herein.

[0027] FIG. 3B illustrates a distal portion of the medical instrument system of FIG. 3Awith an extended example of an instrument in accordance with examples described herein.

[0028] FIG. 4 illustrates an electrode treatment system for delivering a flexible substrate (illustrated in a stowed position) with an electrode to a target region for treatment in accordance with examples described herein.

[0029] FIG. 5 is an enlarged end view of a distal portion of the electrode treatment system of FIG. 4.

[0030] FIG. 6 is an enlarged front view of the distal portion of the electrode treatment system of FIG. 4.

[0031] FIG. 7 illustrates the electrode treatment system of FIG. 4 with the flexible substrate in an expanded position in accordance with examples described herein.

[0032] FIG. 8 illustrates a supporting backbone of the electrode treatment system of FIG. 4 in accordance with examples described herein.

[0033] FIG. 9 illustrates another example of an electrode treatment system for delivering a flexible substrate with an electrode to a target region for treatment, the electrode treatment system including a geared system for controlling drive elements coupled to the flexible substrate.

[0034] FIG. 10 illustrates another example of an electrode treatment system for delivering a multi-segmented flexible substrate with an electrode to a target region for treatment in accordance with examples described herein.

[0035] FIG. 11 illustrates another example of an electrode treatment system for delivering a flexible substrate with an electrode to a target region, the electrode treatment system including an expansion member for aiding in expanding the flexible substrate to an expanded position.DETAILED DESCRIPTION

[0036] Certain details are set forth below to provide a sufficient understanding of embodiments of the disclosure. However, it will be clear to one skilled in the art that embodiments of the disclosure may be practiced without these particular details. Moreover, the particular embodiments of the present disclosure described herein are provided by way of example and should not be used to limit the scope of the claimed subject matter to these particular embodiments. In other instances, well-known materials, components, processes, controller components, software, and / or anatomy have not been described or shown in detail in order to avoid unnecessarily obscuring the embodiments.

[0037] This disclosure is directed to apparatuses and systems for providing controlled delivery of one or more pairs of electrodes to a targeted tissue site for treatment via electroporation and / or electrolysis. Generally, a method for minimally invasive regenerative surgery is disclosed which includes subjecting a target area inliving 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 appreciated that the example systems and methods described herein may be utilized for the deployment of 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.

[0038] During an example procedure, the electrodes are brought into proximity and / or contact with the target tissue, and the electric fields are generated by applying voltages and / or currents between the one or more pairs of electrodes. The electric fields may be generated to have a magnitude to permeabilize cell membranes in a region where ablation is desired. The electric fields may be generated to produce products of electrolysis of a magnitude that, by themselves, do not cause damage to cells or the extracellular matrix. However, when sufficient products of electrolysis are generated in the region of permeabilized cells, cellular death occurs within the region of the applied field without damaging the extracellular matrix or scaffolding to aid in promoting tissue regrowth in the treated tissue region.

[0039] In some examples, the electrodes may be moved to other tissue locations by advancing and / or retracting the electrodes as needed and repeating the process. In this manner, electroporation and / or electrolysis may be performed at multiple locations in a patient to cover a larger area of tissue. In some examples, multiple sets of electrodes may be positioned at multiple respective tissue sites such that electroporation and / or electrolysis may be performed at each site in parallel, reducing and / or eliminating a need to repeat the procedure as a catheter, endoscope, or other suitable medical instrument is moved through the patient.

[0040] In some embodiments of the present disclosure, the systems and methods disclosed herein may be used to treat tissue of the gastrointestinal tract. In other embodiments, any of a variety of tissue may be treated using the systems and methods described herein. Generally, tissue may be treated where tissue regeneration is desirable or where it is desirable to replace one type of cells with another. Examples include intestine, duodenum, stomach, bladder, uterus, endometrial lining, ovaries, colon, rectum, sinuses, ducts, ureters, prostate, skin, muscle, nerve, diaphragm, momentum, kidney, follicles, brain, lymphatic vessels,breast, esophagus, lung, liver, kidney, lymph nodes, lymph node basins and / or heart. Replacement of one type of tissue with another may be in fibrotic areas where it is desired to replace fibrotic cells with stem cells that can remodulate the area or when pancreatic islets are injected in part of the liver to generate new sources of insulin. Other tissue may be treated in other examples. The following provides additional details relating to example processes of electroporation and / or electrolysis for tissue treatment in accordance with some embodiments.

[0041] As noted above, electroporation may be performed to permeabilize the cell membranes of targeted cells. Reversible electroporation may be used in which the permeabilization may cease after the electric fields are removed. Cells may survive reversible electroporation with the pores within the membrane resealing and returning to homeostasis. In some treatment procedures, however, products of electrolysis may be applied to permeabilized cells to cause cell death of the permeabilized cells within the applied electrical field while leaving the extracellular matrix of the permeabilized cells intact. 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) which provide structure for cells and tissues and may additionally provide signaling for cell growth and development. Extracellular matrices may be used as scaffolds for tissue regeneration and / or engineering. For example, cells may be regenerated, grown, transplanted, or otherwise nurtured, on the extracellular matrix. By retaining the extracellular matrix in regions of otherwise ablated cells described herein, cell regeneration and / or tissue engineering may occur in the region of ablated cells. In some procedures, the extracellular matrix may be transplanted from a region of ablated cells to another region (which may be another region of ablated cells), to promote regeneration and / or tissue engineering in the transplanted region. In some cases, once the extracellular matrix is present, material may be injected into the extracellular matrix to enhance regrowth.

[0042] Example systems and methods described herein may utilize electrolysis products to cause cell death together with electroporation to permeabilize the cell membrane. The electrolysis products are sufficient to ablate (e.g., cause cell death) permeabilized cells in a relatively short time frame. However, the concentration of electrolysis products and exposure time are insufficient to cause cell death of non- permeabilized cells, thereby minimizing or avoiding the formation of scar tissue, fibrotictissue, or ulceration in the treated region. Scar tissue and fibrosis is an indication that the extracellular matrix has been affected, and the ability for cells to regenerate and / or tissue engineering to occur in the ablated region may be inhibited. Accordingly, the electrolysis products are used to ablate permeabilized cells only, while leaving the extracellular matrix intact to promote tissue regrowth. Electrolysis products may include products toxic to cells (cytotoxic). Electrolysis preferentially utilizes one or more inert electrodes that do not participate in the process of electrolysis except as a source or sink of electrons or as catalysts. When participating non-inert electrodes are used in the process, they can generate metal ions that may cause systemic damage to the body, such as excess of iron or even metallic fragments.

[0043] Examples of systems disclosed herein include one or more electrodes, a power supply, and a controller to apply energy for treating internal tissue. The energy applied may be electrolysis and / or electroporation in some examples, radiofrequency ablation in other examples, and other energy modalities in yet other examples. When the energy is electroporation with or without electrolysis, the controller controls a charge delivered to the electrode(s) to induce one or more electric fields. When electroporation and electrolysis are included, the electrode(s) are used to generate a current to produce electrolysis products and a voltage difference to produce an electric field that induces electroporation. The duration and magnitude of the charge applied determines the dose of the electrolytic products and the degree of the permeabilization of cells in the treatment site. Accordingly, a region of cell ablation may be determined by a region in which cells are exposed to the combination of permeabilization and to electrolysis products that cause ablation. The ablation, however, may leave the extracellular matrix intact in the region of ablated cells where the electrical field has been applied. The composition of the electrodes may be chosen in accordance with the desired products produced and electroporation effects.

[0044] Examples of systems and methods described herein may utilize a combination of electroporation with electrolysis to facilitate more effective tissue ablation and promote tissue generation in a treatment region. Electroporation, the permeabilization of the cell membrane through the application of electric fields across cell membranes, may be used for tissue ablation with two different sets of electric parameters, those used for reversible electroporation and those used for irreversible electroporation. As mentioned previously, reversible electroporation is the permeabilization of the cell membrane which generally ceases after the electric fieldsare removed and in which the cells survive the application of the electric field. In irreversible electroporation, the permeabilization of the cell membrane is permanent leading to cell death. Accordingly, some electric parameters yield irreversible electroporation in which pores formed in the cell membrane do not reseal after the field is removed, and the permeabilization becomes permanent resulting in electroporated cell death. Typically for biological tissues, electric fields lower than about 1500 V / cm to about 200 V / cm are considered to produce reversible electroporation, while electric fields higher than about 1500 V / cm are considered to produce irreversible electroporation. Examples of systems and methods described herein may utilize reversible electroporation to avoid disadvantages of irreversible electroporation, which may include heating and thermal damage, complexity of providing such large electric fields, and muscle contractions which may result from the large electric fields. It is to be understood that, although systems and methods described herein may be designed to utilize reversible electroporation, there may occur localities or incidental areas where conditions are such that irreversible electroporation, or even thermal ablation, may occur in limited parts of the treated tissue.

[0045] In summary, examples of systems and methods described herein utilize reversible electroporation to permeabilize cells within a targeted area for ablation. The fields used to generate reversible electroporation and / or other electric fields may be used to produce products of electrolysis. The products of electrolysis are introduced into the targeted area to cause ablation of the permeabilized cells, only (e.g., through diffusion across the permeabilized membrane), without affecting non-permeabilized cells and the extracellular matrix. The quantity, concentration, and strength of the electrolysis products provided are such that the extracellular matrix in the region of the permeabilized and ablated cells remains intact and that non-permeabilized cells survive the treatment to promote tissue regrowth. One aim of the combination of cell membrane permeabilization and electrolysis treatment is to minimize or avoid major inflammation, ulceration, and necrosis of tissue at the treatment site, which in turn reduces or eliminates formation of scar and fibrotic tissue and leaves behind a decellularized extracellular matrix suitable for promoting and supporting regeneration of healthy tissue.

[0046] With reference to FIG. 1 , the following provides a brief overview of an example system for delivering a medical instrument with electrodes to a targeted tissue site for treatment via electroporation and / or electrolysis. FIG. 1 is a schematicillustration of a system 10 arranged in accordance with example embodiments described herein. Generally, example systems described herein may include a delivery system and a controller. In the example of FIG. 1 , the system 10 includes a controller 14 and a medical instrument system 40. Examples of other medical instrument systems which may be used with the system 10 (or other suitable systems described herein) are described in further detail below with respect to FIGS. 4-11 . As further described below, the controller 14 may include a processor 16, computer readable media 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. The computer readable media 18 includes executable instructions for causing electroporation and / or electrolysis 20 with the medical instrument system 40 and may include stored parameters 22 which may be used in the process for causing electroporation and / or electrolysis, such as electric field strengths, voltage and / or current levels, waveform shapes, exposure duration parameters, and any other suitable parameters. In the example of FIG. 1 , the circle depicted around an end of the medical instrument system 40 may indicate a region of cells that may be permeabilized via an applied electric field.

[0047] The controller 14 may be implemented using a computing device. Examples of computing devices include controllers, microcontrollers, computers, servers, medical devices, smart phones, tablets, wearable devices, and the like. The computing device may be handheld and may have other uses as well. The controller 14 may include one or more processors, such as the processor 16. Any kind or number of processors may be present, including one or more central processing unit(s) (CPUs) or graphics processing unit(s) (GPUs) having any number of cores, controllers, microcontrollers, and / or custom circuity such as one or more application specific integrated circuits (ASICs) and / or field programmable gate arrays (FPGAs).

[0048] The controller 14 described herein may include computer readable media 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), and the like). While a single box is depicted as the computer readable media 18 in FIG. 1 , any number of computer readable media 18 devices may be present. The computer readable media 18 may be in communication with (e.g., electrically connected to) the processor 16.

[0049] As noted above, the computer readable media 18 may store executable instructions for execution by the processor 16, such as executable instructions for causing electroporation and / or electrolysis 20 with the medical instrument system 40 and may utilize stored parameters 22 for the medical instrument system 40. In this manner, techniques for applying electroporation and / or electrolysis in tissue may be implemented herein wholly or partially in software.

[0050] The executable instructions 20 may include instructions to control a charge delivered to electrodes, such as electrodes 50 of the medical instrument system 40. Accordingly, the controller 14 may induce a voltage difference across the targeted tissue to generate an electric field that causes permeabilization of cells in an area of tissue targeted for treatment. In the illustrated embodiment, the electrodes 50 may be disposed on a flexible substrate (e.g., flexible substrate 422 of FIG. 4) of the medical instrument system 40 as described in further detail with particular reference to the medical instrument system 400 of FIGS. 4-7. The electrodes 50 are illustrated in a cavity or lumen 32 formed within tissue 30. Although the medical instrument system 40 is shown disposed within a cavity 32 of tissue 30, the medical instrument system 40 may be on the surface of the tissue 30, inside the tissue 30, and / or proximate to the tissue 30.

[0051] A controller, such as controller 14 of FIG. 1 , may activate one or more selected electrodes 50 to provide an electric field. In some embodiments, the controller 14 may alternate or otherwise select a pattern of activated electrodes 50 (e.g., activating pairs of electrodes in sequence) to shape or deliver a particular electric field. In some examples, fluids or other substances may be injected into, brought into contact with, or otherwise placed in or around the tissue 30 to aid in shaping the electric field generated in the tissue 30. For example, conductive fluids may aid in shaping the field (e.g., by extending the field). In other examples, non-conductive fluids may aid in shaping the field (e.g., by attenuating the field). In some examples, non-conductive fluids or other substances may be injected or otherwise placed in tissue to protect areas where ablation is not desired. The electric field may not penetrate and / or not be carried through the non-conductive fluid, such that the field would not reach tissue where ablation is not desired, or at least be present in insufficient strength to cause permeabilization or other cellular change.

[0052] The controller 14 may also be used to induce a current through the tissue 30, such as between electrodes 50, to generate products of electrolysis. The productsof electrolysis may cause ablation of the permeabilized cells but are preferably insufficient to destroy the extracellular matrix in the region of the permeabilized cells. The remaining intact extracellular matrix may allow for regeneration of the tissue and tissue engineering as described previously.

[0053] In some embodiments, one or more of the electrodes 50 used to apply electroporation may also be used to generate products of electrolysis (in other words, some or all of the electrodes may be used for both electroporation and / or electrolysis). In other embodiments, a first subset of electrodes 50 used to apply electroporation may be different from a second subset of electrodes 50 used to generate products of electrolysis.

[0054] In some embodiments, the power supply 12 is integrated with the controller 14. The power supply 12 may be implemented using any suitable power source, such as one or more AC power sources, DC power sources, batteries, and / or waveform generators. The power supply 12 may supply power to the electrodes 50 to generate a voltage and / or current and, therefore, an electric field and / or electrolysis products in the tissue 30. In some examples, the power supply 12 may be implemented using a signal generator, such as an exponential decay wave generator (by way of example, a Harvard Apparatus BTX 630), however, this disclosure is not limited thereto or thereby.

[0055] The controller 14 may control the timing, strength, and duration of electric fields and / or electrolysis products provided via the medical instrument system 40. The controller 14 may, for example, be programmed to provide an electronic signal to the medical instrument system 40, via the power supply 12, where the electronic signal may be indicative of a dose of treatment, for example, a dose of electrolysis products and / or permeability level of cell. The electronic signal may control the timing and magnitude of the generated electric field, which may allow a user to customize treatment of the tissue 30 as desired. In some embodiments, the controller 14 may include such a program, or include one or more processing devices (e.g., processors), coupled to the computer readable media 18 encoded with executable instructions for electrolysis and permeabilization 20. Although shown as a separate component coupled to the medical instrument system 40 in FIG. 1 , in some embodiments, the controller 14 may be integrated as part of the medical instrument system 40. In other embodiments, the controller 14 may include programmable circuitry coupled to the medical instrument system 40 via a wired or wireless connection.

[0056] As noted previously, the system 10 may include any suitable parameters 22 for controlling various aspects of the electroporation and / or electrolysis processes, such as electric field strengths, voltage levels, current levels, waveform shapes, exposure duration parameters, and any other suitable parameters. The parameters 22 may be stored in computer readable media 18 or in other suitable databases in communication with the controller 14. In some embodiments, the controller 14 may be used to calculate the parameters 22, or the controller 14 may be in communication with another system operable to calculate the parameters 22.

[0057] In some example embodiments, the parameters 22 for a specific treatment protocol may be determined based on measurements taken in the tissue of interest or from a different sample of similar tissue. For example, measurements may be taken at various voltage levels with particular electrode configurations, and a target voltage level, current, pulse pattern, time constant, and other factors may be identified which cause reversible electroporation and the delivery of electrolysis products to result in cell death of the permeabilized cells as desired.

[0058] In some embodiments, examples of parameters 22 which may be used include a delivery of between 1 and 50 voltage pulses between 50 V and 1000 V. Those pulses may be delivered in a system having a capacitance between 50 pF and 1000 pF, and a resistance of between 15-20 ohms. A quantity of electrolysis products generated may be related to the delivered charge in Coulombs. There are several ways to calculate the delivered charge. For example, the stored electric charge in a capacitor, Q (in coulombs, abbreviated C) is equal to the product of the capacitance C (in Farads, abbreviated F) of the capacitor, and the voltage V (in volts, abbreviated V) across its terminals. That is, Q = C *V. also, Current x time = charge. I.t = Q. By defining the capacitance and the voltage across the capacitance, the charge may be defined, and accordingly the electrolysis performance determined. When a capacitor is discharged, it generates current and the current multiplied by time must be equal to the charge in the capacitor. When a capacitor is being discharged the current is not constant - it decays exponentially. Therefore, the time measure is given as the exponential decay time constant. The capacitance which controls the time constant is generally obtained from capacitors incorporated in the power supply, such as power supply 12 of FIG. 1.

[0059] In some embodiments, the time constant (e.g., exponential decay time constant of the capacitive discharge) may range from 50 ps to 3ms. Generally, the lower limit of the time constant is related to a time sufficient to ensure electrolytic species (e.g., products of electrolysis) permeate the targeted area of permeabilized cells. The upper limit of the time constant is generally related to the production of electrolytic species (e.g., products of electrolysis) that can cause ablation on their own. Accordingly, electrolysis is generally targeted for an amount of time sufficient to allow diffusion of electrolysis products through a region of permeabilized cells. However, the amount of time electrolysis is provided should be limited to ensure the process does not result in ablation of non-permeabilized cells or otherwise damages the extracellular matrix in the region of the ablated cells.

[0060] In some embodiments, the generated electric field ranges between 100 V / cm and 3500 V / cm. In other embodiments, the electric field may be between 100 V / cm and 1500 V / m or between 200 V / cm and 850 V / cm. In still other embodiments, the electric field may 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.

[0061] The system 10 may further include one or more sensors (not shown) for measurement of pH, electric field strength, and / or other suitable properties of the tissue 30 for optimizing treatment. For example, in one embodiment, a pH sensor may be incorporated with the system 10. The pH sensor may be arranged in any one of several configurations, such as coupled to the medical instrument system 40 adjacent the electrodes 50 to detect a pH value near the electrodes 50. In another embodiment, a pH sensor may be provided at an outer edge of a targeted region of tissue. In either configuration, the pH sensor may be in communication with the controller 14, where the controller 14 may utilize one or more received pH values as an indication of tissue ablation and / or to monitor the occurrence of tissue damage based on detected pH levels at the treatment site and surrounding regions of tissue. In some embodiments, the controller 14 may adjust the voltage, current, and / or electric field applied to the tissue responsive to the detected pH levels. For example, if pH values for tissue located outside the treatment site are at or exceed a threshold for tissue damage, the controller 14 may reduce a magnitude of electric field, a duration between pulses, or cease application of the electric field. Similarly, if pH values for tissue within a targeted region are at or exceed a threshold for tissue ablation, the controller 14 may ceaseapplication of current through electrodes immediately and / or after a desired elapsed electrolysis time to cease the electrolysis process.

[0062] In some embodiments, a resistivity meter may be used to determine a resistance of the target tissue. For example, the controller 14 and / or power supply 12 of FIG. 1 may provide an impedance measurement. The impedance measurement may determine a resistivity of the tissue 30 contacted by electrodes 50 of the system 10. For example, the controller 14 and / or power supply 12 may provide a nominal amount of current, such as DC current, through the tissue 30 and receive a resistivity measurement and / or calculate resistivity of the tissue 30. In some examples, an applied voltage, current, and / or electric field may be selected, determined, and / or allowed based on a measured resistance of the tissue 30. In some examples, a number of pulses of applied voltage may be selected, determined, and / or otherwise used based on a measured resistance of the tissue.

[0063] In some embodiments, a sensor, such as a Gauss meter and / or Tesla meter, for detecting and / or determining electric field strength may also be used. In such embodiments, the sensor may be in operable communication with the controller 14 for ensuring that the electric field strength remains at a target level for a desired treatment protocol.

[0064] In some embodiments, the ablation instrument for delivering electrolytic electroporation (e.g., medical instrument system 40 of FIG. 1 ) may be delivered via a computer-assisted, teleoperational manipulator system, sometimes referred to as a robotically assisted system or a robotic system. The manipulator system comprises one or more manipulators that can be operated with the assistance of an electronic controller (e.g., computer) to move and control functions of one or more instruments when coupled to the manipulators. FIG. 2 illustrates one example embodiment of a robotically-assisted manipulator system 100 for use with the systems and methods described herein. The manipulator system can be used, for example, in surgical, diagnostic, therapeutic, biopsy, or non-medical procedures.

[0065] With reference to FIG. 2, a robotically-assisted manipulator system 100 may include one or more manipulator assemblies 102 for operating one or more medical instrument systems 104 in performing various procedures on a patient P positioned on a table T in a medical environment 101. For example, the manipulator assembly 102 may drive medical instrument or end effector motion, may apply treatment to target tissue, and / or may manipulate control members. The manipulator assembly 102 maybe teleoperated, non-teleoperated, or a hybrid teleoperated and non-teleoperated assembly with select degrees of freedom of motion that can be motorized and / or teleoperated and select degrees of freedom of motion that may be non-motorized and / or non-teleoperated. An operator input system 106, which may be inside or outside of the medical environment 101 , generally includes one or more control devices for controlling manipulator assembly 102. The manipulator assembly 102 supports a medical instrument system 104 and may optionally include a plurality of actuators or motors that drive inputs on the medical instrument system 104 in response to commands from a control system 112. The actuators may optionally include drive systems that when coupled to the medical instrument system 104 advance the medical instrument system 104 into a naturally or surgically created anatomic orifice. Other drive systems can move the distal end of the medical instrument system 104 in multiple degrees of freedom, which may include three degrees of linear motion (e.g., linear motion along the X, Y, Z Cartesian axes) and in three degrees of rotational motion (e.g., rotation about the X, Y, Z Cartesian axes). The manipulator assembly 102 may support various 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.

[0066] The robotically-assisted manipulator system 100 also includes a display system 110 for displaying an image or representation of the surgical site and the medical instrument system 104 generated by an imaging system 109 which may include an imaging system, such as an endoscopic imaging system. The display system 110 and the operator input system 106 may be oriented so an operator O can control the medical instrument system 104 and the operator input system 106 with the perception of telepresence. A graphical user interface may be displayable on the display system 110 and / or a display system of an independent planning workstation.

[0067] In some examples, the endoscopic imaging system components of the imaging system 109 may be integrally or removably coupled to the medical instrument system 104. However, in some examples, a separate imaging device, such as an endoscope, attached to a separate manipulator assembly may be used with the medical instrument system 104 to image the surgical site. The endoscopic imaging system 109 may be implemented as hardware, firmware, software, or a combinationthereof which interact with or are otherwise executed by one or more computer processors, which may include the processors of the control system 112.

[0068] The robotically-assisted manipulator system 100 may also include a sensor system 108. The sensor system 108 may include a position / location sensor system (e.g., an actuator encoder or an electromagnetic (EM) sensor system) and / or a shape sensor system (e.g., an optical fiber shape sensor) for determining the position, orientation, speed, velocity, pose, and / or shape of the medical instrument system 104. The sensor system 108 may also include temperature, pressure, force, or contact sensors or the like.

[0069] The robotically-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 effecting control between the medical instrument system 104, the operator input system 106, the sensor system 108, and the display system 110. The control system 112 also includes programmed instructions (e.g., a non-transitory machine-readable medium storing the instructions) to implement a procedure using the robotically-assisted manipulator system including for navigation, steering, imaging, engagement feature deployment or retraction, applying treatment to target tissue (e.g., via the application of energy), or the like.

[0070] The control system 112 may optionally further include a virtual visualization system to provide navigation assistance to operator O when controlling the medical instrument system 104 during an image-guided surgical procedure. Virtual navigation using the virtual visualization system may be based upon reference to an acquired pre-operative or intra-operative dataset of anatomic passageways. The virtual visualization system processes images of the surgical site imaged using imaging technology such as computerized tomography (CT), magnetic resonance imaging (MRI), fluoroscopy, thermography, ultrasound, optical coherence tomography (OCT), thermal imaging, impedance imaging, laser imaging, nanotube X-ray imaging, and / or the like. The control system 112 may use a pre-operative image to locate the target tissue (using vision imaging techniques and / or by receiving user input) and create a pre-operative plan, including an optimal first location for performing treatment. The pre-operative plan can include, for example, a planned size to expand an expandable device, a treatment duration, a treatment temperature, and / or multiple deployment locations.

[0071] FIG. 3A illustrates a medical instrument system 200 according to some example embodiments. The medical instrument system 200 may be used in an image- guided medical procedure. In some embodiments, the medical instrument system 200 may be used for non-teleoperational exploratory procedures or in procedures involving traditional manually operated medical instruments, such as endoscopy. In other embodiments, the medical instrument system 200 is interchangeable with, or a variation of, the medical instrument system 104 of FIG. 2.

[0072] The medical instrument system 200 includes an elongate flexible device 202, such as a flexible catheter, an endoscope (e.g., duodenoscope, gastroscope, bronchoscope), or other suitable member coupled to a drive unit 204. The elongate flexible device 202 includes a flexible body 216 having a proximal end portion 217 and a distal end 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 larger or smaller outer diameters. The flexible body 216 may have an appropriate length to reach certain portions of the anatomy, such as the lungs, sinuses, throat, or the upper or lower gastrointestinal region, when the flexible body 216 is inserted into a patient’s oral or nasal cavity.

[0073] The medical instrument system 200 optionally includes a tracking system 230 for determining the position, orientation, speed, velocity, pose, and / or shape of the distal end portion 218 and / or of one or more segments 224 along the flexible body 216 using one or more sensors and / or imaging devices. The entire length of the flexible body 216, between the distal end portion 218 and the proximal end portion 217, can be effectively divided into segments 224. The tracking system 230 may optionally be implemented as hardware, firmware, software or a combination thereof which interact with or are otherwise executed by one or more computer processors, which may include the processors of the control system 112 in FIG. 2.

[0074] The tracking system 230 may optionally track the distal end portion 218 and / or one or more of the segments 224 using a shape sensor 222. In some embodiments, the tracking system 230 may optionally and / or additionally track the distal end portion 218 using a position sensor system 220, such as an electromagnetic (EM) sensor system. In some examples, the position sensor system 220 may be configured and positioned to measure six degrees of freedom, e.g., three position coordinates X, Y, Z and three orientation angles indicating pitch, yaw, and roll of abase point or five degrees of freedom, e.g., three position coordinates X, Y, Z and two orientation angles indicating pitch and yaw of a base point.

[0075] The flexible body 216 includes one or more channels (e.g., passageways) sized and shaped to receive one or more medical instruments 226. In some embodiments, the flexible body 216 includes two channels 221 for separate instruments 226, however, a different number of channels 221 may be provided. FIG. 3B is a simplified diagram of an end portion of the flexible body 216 with the medical instrument 226 extended outwardly therefrom according to some embodiments. In some embodiments, the medical instrument 226 may be used for procedures and aspects of procedures, such as surgery, biopsy, ablation, mapping, imaging, illumination, irrigation, or suction. The medical instrument 226 may be deployed through the channel 221 of the flexible body 216 and used at a target location within the anatomy. The medical instrument 226 can include, for example, image capture devices, biopsy instruments, ablation instruments, catheters, laser ablation fibers, and / or other surgical, diagnostic, or therapeutic tools. Medical tools can include end effectors having a single working member such as a scalpel, a blunt blade, a lens, an optical fiber, an electrode, and / or the like. Other end effectors can include, for example, forceps, graspers, balloons, needles, scissors, clip appliers, and / or the like. Other end effectors can further include electrically activated end effectors such as electrosurgical electrodes, transducers, sensors, imaging devices and / or the like. The medical instrument 226 may be advanced from the opening of channel 221 to perform the procedure (e.g., electroporation and / or electrolysis in the present disclosure) and then retracted back into the channel 221 when the procedure is complete. The medical instrument 226 may be removed from the proximal end portion 217 of the flexible body 216 or from another optional instrument port (not shown) along the flexible body 216. The medical instrument 226 may be used with an image capture device (e.g., an endoscopic camera) also within the elongate flexible device 202. Alternatively, the medical instrument 226 can itself be the image capture device.

[0076] The medical instrument 226 may additionally house cables, linkages, or other actuation controls (not shown) that extend between its proximal and distal end portions 217, 218 to controllably bend the distal end portion 218 of the medical instrument 226. The flexible body 216 may also house cables, linkages, or other steering controls (not shown) that extend between the drive unit 204 and the distal end portion 218 to controllably bend the distal end portion 218 as shown, for example, bythe broken dashed line depictions 219 of the distal end portion 218. In some examples, at least four cables are used to provide independent “up-down” steering to control a pitch motion of the distal end portion 218 and “left-right” steering to control a yaw motion of the distal end portion 218. In embodiments in which the medical instrument system 200 is actuated by a robotically-assisted assembly, the drive unit 204 can include drive inputs that removably couple to and receive power from drive elements, such as actuators, of the teleoperational assembly. In some embodiments, the medical instrument system 200 can include gripping features, manual actuators, or other components for manually controlling the motion of the medical instrument system 200. The information from the tracking system 230 can be sent to a navigation system 232 where it is combined with information from the visualization system 231 and / or the preoperatively obtained models to provide the physician or other operator with real-time position information.

[0077] In some embodiments, the medical instrument system 200 may be guided manually or via the robotically-assisted manipulator system 100 to deliver the medical instrument 226 to a target tissue site for treatment. In some procedures, the selection between a manual or robotic delivery and the approach may be determined based on the medical application. For example, in some gastrointestinal applications, the medical instrument system 200 (or standalone medical instrument 226) may be delivered via a manual or robotic delivery device endoluminally through a trans-oral or trans-anal approach. A trans-abdominal approach with integrated bipolar instrumentation, drop in probes or via catheters may also be used. For urological applications, the medical instrument system 200 (or standalone medical instrument 226) may be delivered via a manual or robotic delivery device endoluminally through a trans-urethral approach, trans-perineal, pre-peritoneal or trans-abdominally with integrated bipolar instrumentation, drop in probes or via catheters. Similarly, for gynecological applications, the medical instrument system 200 (or standalone medical instrument 226) may be delivered via a manual or robotic delivery device endoluminally through a trans-vaginal approach, trans-perineal, or trans-abdominally with integrated bipolar instrumentation, drop in probes or via catheters. For hepatobiliary applications, the medical instrument system 200 (or standalone medical instrument 226) may be delivered via a manual or robotic delivery device endoluminally through a trans-oral approach to reach the ampulla or to go externally into the liver via a trans-gastrointestinal wall route or trans-abdominally with integratedbipolar instrumentation, drop in probes or via catheters. For neurovascular applications, the medical instrument system 200 (or standalone medical instrument 226) may be delivered via a manual or robotic delivery device through an endovascular approach or through a keyhole craniotomy with integrated bipolar instrumentation, drop in probes or via catheters. For cardiac applications, the medical instrument system 200 (or standalone medical instrument 226) may be delivered via a manual or robotic delivery device through an endovascular approach or trans-thoracic with integrated bipolar instrumentation, drop in probes or via catheters.

[0078] With collective reference to FIGS. 4-11 , the following provides additional details of various embodiments and features relating to electrode treatment system designs and various components thereof that may be used together with the system 10, the robotically-assisted manipulator system 100, and / or the medical instrument system 200 described previously with reference to FIGS. 1 -3B. Generally, the electrode treatment systems described with reference to FIGS. 4-11 are designed to maintain an overall compact, low-profile for the medical instrument to facilitate delivery to the target tissue site and retraction after treatment. Other features and advantages of the electrode treatment system designs are further described below with reference to the figures.

[0079] FIGS. 4-7 collectively illustrate an electrode treatment system 400 operable for delivering a flexible substrate 422 bearing an electrode 424 to a target tissue region (e.g., tissue 30 of FIG. 1 ) in accordance with an example embodiment. The electrode treatment system 400 may be used to provide electrolysis and / or electroporation treatment to the target tissue region, such as for duodenal mucosal resurfacing in the gastrointestinal tract, according to example embodiments of the present disclosure.

[0080] With general reference to FIG. 4, the electrode treatment system 400 includes an elongate flexible member 402, such as a flexible catheter, an endoscope (e.g., duodenoscope, gastroscope, bronchoscope) or other suitable member, with 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 in length. Other embodiments of the flexible housing 404 may include larger or smaller outer diameters, which may depend on the target anatomy for treatment (e.g., between 2 mm and 12 mm). The flexible housing 404 may have an appropriate length to reach certain portions of the anatomy, such as the lungs, sinuses, throat, or the upper or lower gastrointestinal region, when the elongate flexible member 402 isinserted into a patient’s oral or nasal cavity (or otherwise introduced, such as via a surgical incision). In some embodiments, the length of the elongate flexible member 402 may range between 85 cm and 300 cm (or have another suitable length) to reach a desired anatomical tissue region for treatment. It should be understood that in other embodiments, the elongate flexible member 402 and its components may have any suitable dimensions that may depend on the target tissue region, surrounding anatomical structures, or other suitable factors.

[0081] FIG. 5 is an enlarged end view of the distal portion 408 of the electrode treatment system 400. With particular reference to FIG. 5, the housing 404 includes a first working channel 410 with an opening on a distal face 412 of the housing 404. In some example systems, the first working channel 410 may have a generally oval or kidney-shaped profile as illustrated. In other embodiments, the working channel 410 may have other suitable profiles. As illustrated in FIG. 5, the first working channel 410 includes a first seat 414 and a second seat 416 laterally offset from one another, with a ridge or raised portion 418 positioned therebetween. As is further described in detail below, the first seat 414 and the second seat 416 each receive a wrapped or furled portion of a flexible substrate 422. The distal face 412 of the housing 404 may further include a second working channel 420 with a second opening on the distal face 412 of the housing 404, where the second working channel 420 is offset from the first working channel 410 on the distal face 412. In some example embodiments, the distal face 412 of the housing 404 may include any number of working channels (e.g., 421 a, 421 b, 421c, 421 d) with respective openings on the distal face 412 of the housing 404, in addition to those specifically described herein for supporting other features of the electrode treatment system 400, such as imaging devices, sensing devices, lighting, suction systems, irrigation systems, and the like.

[0082] The electrode treatment system 400 further includes a flexible substrate 422 that may be a thin layer or sheet comprised 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 comprise a polymer covered material. The flexible substrate 422 includes an electrode 424 deposited or otherwise supported thereon, where the electrode 424 is suitable for providing one or both of electrolysis and / or electroporation to the targeted tissue in a similar fashion as described previously. Accordingly, the electrode 424 may take any suitable configuration operable for generating an electric field. For example, in oneembodiment, the electrode 424 may comprise a plurality of metal traces deposited on the flexible substrate 422. The metal traces may include any suitable conductive material such as gold, copper, stainless steel, titanium, graphene, graphite, and the like. Generally, electrode materials may be selected such that the electrode material does not actively participate in electrolysis products and / or leave material residue. In some embodiments, the electrode material may be chosen to minimize transferring ions from the electrode material to the target tissue. While titanium and gold may participate in the electrolysis process to some degree, they may not generate a toxic residue and thus may be preferred in some examples. In other embodiments, the electrode 424 may comprise other suitable shapes and configurations, including circular, square, rectangular, or other shapes for the electrodes. Interdigitated electrodes may also be used. Electrodes as disclosed herein can be one, two, or another suitable number of electrodes. The electrodes can form or be part of an electrode array.

[0083] Generally, the electrodes 424 used in the example configurations described herein are arranged in a bipolar configuration. Generally, in a bipolar configuration, current may travel from one electrode of a pair of electrodes to a second electrode in the pair of electrodes. The electrodes in the pair of electrodes may accordingly be of opposite polarity. In some configurations, multiple pairs of electrodes may be used, with the current passing through each respective pair of electrodes.

[0084] In other examples, the electrodes of the electrode 424 may be arranged in a monopolar configuration or may be arranged in a combination of bipolar and monopolar configurations. A monopolar configuration may include an active electrode (e.g., an electrode on or in the surgical field) and a return electrode. The return electrode may be placed outside the surgical field but in contact with the patient in some examples (e.g., using a pad having an electrode). In this manner, one polarity (e.g., the polarity of the active electrode) is in the surgical field. Accordingly, a monopolar configuration of electrodes may include a pair of electrodes - with one energized and one serving as a return. The return electrode may not be provided on a same device as the energized electrode. For example, the return electrode may be provided on a pad placed proximate the tissue. In a monopolar configuration, multiple active electrodes may be present and may pass current through a shared return electrode in some examples, or through multiple respective return electrodes in other examples.

[0085] The electrode treatment system 400 further includes suitable wiring, circuitry, and other electronic components (not shown) for providing electrical signals, such as voltages and / or currents, to the electrode 424. In one embodiment, the wiring may run down or otherwise extend the length of the elongate flexible member 402 to the controller 14 and / or power supply 12 (see FIG. 1 ), which may be outside the body. In other embodiments, other suitable wiring configurations may be used to power the electrode 424.

[0086] Returning to FIG. 4, the flexible substrate 422 is coupled to a drive system 428 operable to control deployment and retraction of the flexible substrate 422 (and by extension, the electrode 424 deposited or otherwise supported thereon) as further described in detail below (e.g., with collective reference to FIGS. 4-7). In one example embodiment, the drive system 428 includes a first drive element 430, such as an elongate flexible drive shaft or other suitable elongate member capable of transmitting mechanical power, torque, and rotation. The first drive element 430 includes a proximal portion 432 that may be coupled to a drive 434 (e.g., a motor and / or motor drive) and an opposite distal portion 436 extending into the housing 404 and coupled to a first portion of the flexible substrate 422. The drive system 428 further includes a second drive element 438 with features and characteristics similar or identical to the first drive element 430. The second drive element 438 includes a proximal portion 440 that may be coupled to a drive 442 (e.g., a motor and / or motor drive) and an opposite distal portion 444 extending into the housing 404 and coupled to a second portion of the flexible substrate 422 in a similar or identical fashion as the first drive element 430. In some embodiments, the drives 434, 442 may be independently controllable (such as via the manipulator assembly 102, the operator input system 106, the control system 112, or other suitable processing systems) to drive the drive elements 430, 438 independently of one another as further described in detail below (e.g., with particular reference to FIG. 7). It should be understood that in other embodiments, the drive elements 430, 438 may instead be coupled to and controlled by a single drive (as opposed to two separate drives 434, 442) operable to drive the drive elements 430, 438 independently or concurrently. In some embodiments, the electrode treatment system 400 and other electrode treatment systems described herein may be actuated manually by a user. In other embodiments, the electrode treatment systems may be coupled to an external device for actuation such as a robotically-assisted manipulator system (e.g., robotically-assisted manipulator system 100). In yet other embodiments, manual and robotically-assisted actuation may be provided.

[0087] The electrode treatment systems described herein may be coupled to an external device to provide actuation, control, and / or electrical power to the electrode treatment system. For example, the electrode treatment system 400 and the other electrode treatment systems described herein may be actuated by a robotically- assisted manipulator system (e.g., manipulator assembly 102). The electrode treatment system 400 (e.g., elongate flexible member 402, housing 404, and / or drive element(s) 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 proximal portion(s) 432, 440) that removably couple to and receive power from drive elements, such as actuators, motors, and the like, of the manipulator assembly 102. When the electrode treatment system 400 is coupled to the manipulator assembly 102, the drive inputs of the electrode treatment system 400 may be coupled to drive outputs of the manipulator assembly 102 that are driven by the drive elements of the manipulator assembly 102. Such drive elements of the manipulator assembly 102 can be or otherwise include the drives (e.g., drive 434, 442) of electrode treatment system 400. In such embodiments, the drives 434, 442 of the electrode treatment system 400 and other electrode treatment systems described herein can be located on, in, or otherwise be operably coupled to the manipulator assembly 102. In addition, the drive inputs of the electrode treatment system 400 may be coupled to the distal end portion of the electrode treatment system 400 via one or more actuation drive members or elements (e.g., drive shafts, actuation cables, actuation rods, tension members, and the like) to perform actions such as advancing, retracting, or articulating the distal end of the electrode treatment system 400 as well as expansion, deployment, and / or retraction of the flexible substrate 422 described herein to adjust the electrode 424 between an expanded position for treatment and a stowed position for retraction. In some embodiments, the drive elements 430, 438 of the electrode treatment system 400 may be coupled to the drive unit 204 for adjusting the flexible substrates (e.g., flexible substrate 422) between the expanded and contracted positions. In addition, the drive unit 204 may be coupled to a controller (e.g., controller 14) and / or power supply (e.g., power supply 12) to provide electrical power to electrodes of electrode treatment system 400 as described above. The drive unit 204 may be electrically coupled to the electrodes via one or more electrical cables running along or through the electrode treatment system 400. Inalternative embodiments, the controller and power supply may provide power to the electrical cables without coupling to the drive unit (e.g., the controller and power supply may be independent of the drive unit).

[0088] As noted above, the drive elements 430, 438 are coupled to the flexible substrate 422 and actuatable to deploy the flexible substrate 422 from the housing 404. With collective reference to FIGS. 5 and 6, the following provides details of an example coupling arrangement of the flexible substrate 422 and the drive elements 430, 438. With particular reference to FIG. 5, the flexible substrate 422 includes a first portion 446 (e.g., a first end of the flexible substrate 422) coupled to the distal portion 436 of the first drive element 430 and a second portion 448( e.g., a second end of the flexible substrate 422 opposite of the first end) coupled to the distal portion 444 of the second drive element 438. The flexible substrate 422 may be coupled in any suitable fashion to the drive elements 430, 438. For example, in one embodiment, the first drive element 430 and the second drive element 438 may each include a channel 450, 452, respectively, formed along the respective distal portions 436, 444, where the first portion 446 of the flexible substrate 422 extends into the channel 450 of the first drive element 430 and the second portion 448 of the flexible substrate 422 extends into the channel 452 of the second drive element 438. In this configuration, the first and second portions 446, 448 of the flexible substrate 422 may be bonded (e.g., via an adhesive or other suitable material) in place to the respective drive elements 430, 438. In other embodiments, the first and second portions 446, 448 of the flexible substrate 422 may instead be wrapped partially or entirely around the respective distal portions 436, 444 of the drive elements 430, 438 and bonded in place in addition to or instead of extending into channels 450, 452 of drive elements 430, 438. Other embodiments may use other suitable coupling arrangements.

[0089] With reference to FIG. 5, when the flexible substrate 422 is in the stowed position within the housing 404, a first furled section 454 of the flexible substrate 422 encircles the distal portion 436 of the first drive element 430 and a second furled section 456 of the flexible substrate 422 encircles the distal portion 444 of the second drive element 438. Preferably, the first furled section 454 and the second furled section 456 are wrapped in opposite directions relative to one another around the respective first drive element 430 and the second drive element 438 to facilitate deployment and retraction and / or removal as described in further detail below. In this configuration, an unfurled section 458 of the flexible substrate 422 extends betweenthe first furled section 454 and the second furled section 456 as illustrated. In one example embodiment, the first furled section 454 of the flexible substrate 422 is received within the first seat 414 of the working channel 410 and the second furled section 456 of the flexible substrate 422 is received within the second seat 416 of the working channel 410, where the first furled section 454 is laterally offset from the second furled section 456 within the working channel 410 as illustrated. As illustrated, the first furled section 454 encircles the distal portion 436 of the first drive element 430 about a first rotational axis A. The second furled section 456 encircles the distal portion 444 of the second drive element 438 about a second rotational axis B that is spaced apart or otherwise offset (e.g., parallel) from the first rotational axis A.

[0090] In some embodiments, the flexible substrate 422 may have a length of approximately 20 mm when in a flattened and relaxed configuration. In other embodiments, the flexible substrate 422 may have an axial length ranging from 10-40 mm. When in the stowed position, the first furled section 454 and the second furled section 456 may each have a substantially equal diameter relative to one another. In other embodiments, the diameter may differ slightly as between the furled sections 454, 456. In some examples, the diameter for each furled section 454, 456 may be approximately 6 mm across, with the flexible substrate 422 measuring a total of approximately 12 mm across when the two furled sections 454, 456 are arranged in a dual-wrapped configuration as illustrated. In other embodiments, the first furled section 454 and the second furled section 456 may each have a diameter ranging from approximately 2 mm to 12 mm.

[0091] In some embodiments, the electrode treatment system 400 may further include a sheath 460 disposed within the housing 404, where the sheath 460 supports the flexible substrate 422. In one example embodiment, the sheath 460 may be coupled to or may be formed as an integral portion of the working channel 410, such that the sheath 460 is in operable communication with the working channel 410. In such embodiments, the sheath 460 may include the first seat and the second seat (e.g., seats 414, 416) upon which the flexible substrate 422 is received, where the seats of the sheath 460 otherwise have similar features and functionality as described above. In some embodiments, the sheath 460 further helps retain the flexible substrate 422 in its rolled configuration relative to the drive elements 430, 438 when the flexible substrate 422 is in the stowed position within the housing 404. As illustrated in FIG. 6, the sheath 460 may have a generally oval profile matching that ofthe flexible substrate 422 when in the stowed position, wherein the flexible substrate 422 is securely received within the sheath 460 and held in position therein until deployment.

[0092] With general reference to FIGS. 4-7, the following describes an example delivery procedure of the electrode treatment system 400 to a target tissue site and an example deployment of the flexible substrate 422 and electrode 424 in accordance with an example embodiment. In one example, the electrode treatment system 400 (e.g., endoscope) may be delivered in a trans-oral manner to the duodenum for ablation of mucosal lining (or other tissue site). For this procedure, delivery may include entry through the patient’s esophagus, navigation through the stomach, and finally into the duodenum for treatment. With the electrode treatment system 400 in position at the duodenum, the drives 434, 442 axially move (e.g., translate) the respective drive elements 430, 438 relative to the housing 404 and drive the first furled section 454 and the second furled section 456, respectively, of the flexible substrate 422 through the opening of the working channel 410 and outwardly of the distal face 412 of the housing 404. In embodiments where the electrode treatment system 400 includes a sheath 460 coupled to (or integrally formed with) the working channel 410, the drive elements 430, 438 are axially moved through the sheath 460 and distally of the housing 404 in a similar fashion as described.

[0093] With particular reference to FIG. 7, the drive elements 430, 438 are moved axially through the working channel 410 until the flexible substrate 422 is clear of the distal face 412 of the housing 404 (e.g., spaced distally from the distal face 412) to accommodate deployment. In some embodiments, the flexible substrate 422 is spaced apart from the distal face 412 of the housing 404 by approximately 2 mm to 100 mm. In some embodiments, the flexible substrate 422 may be spaced a sufficient distance away from the distal face 412 of the housing 404 to allow for visualization of the flexible substrate 422 through an imaging system, a 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 may help ensure that the electrode 424 is in proper position relative the tissue for treatment, and may also help facilitate retraction of the flexible substrate 422, such as to ensure that tissue is not pinched or caught by any components of the electrode treatment system 400 during the retraction process.

[0094] As illustrated in FIG. 7, once the flexible substrate 422 is positioned distally of the housing 404 and in position at the target tissue site, the first furled section 454 and the second furled section 456 may be unfurled 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 may be counterrotated relative to one another (e.g., about respective axes A and B) via the drive system 428 to separately unfurl the first furled section 454 from the first drive element 430 and the second furled section 456 from the second drive element 438. The drive elements 430, 438 may be actuated simultaneously to ensure substantially symmetrical deployment of the flexible substrate 422 in some embodiments. As described previously, the first furled section 454 and the second furled section 456 are wrapped in opposite directions relative to one another such that counterrotation of the drive elements 430, 438 deploys the flexible substrate 422 from the stowed position (illustrated in FIG. 5) to an expanded position (see FIG. 7).

[0095] In some embodiments, the top and bottom surfaces of the flexible substrate 422 may be coated with a suitable polymer material (or may be made from such material) to reduce frictional forces from the overlapping portions of the flexible substrate 422 when in the stowed position to facilitate unfurling via the drive elements 430, 438. The protective coating layer may also cover some or all of the electrode 424 disposed on the flexible substrate 422. In these embodiments, the protective coating layer may include silicone, parylene, or other suitable coatings. Both silicone and parylene may act as suitable insulators in cases where the electrode 424 is underdeployed to minimize potential complications. In some embodiments, the inner lubricity created by the protective coating layer may facilitate smooth deployment and unfurling of the flexible substrate 422, as it may act to reduce friction between overlapping sections of the flexible substrate 422, especially where the material comprising the flexible substrate 422 may be somewhat sticky or tacky. In addition, the protective coating layer may also help prevent the electrode 424 from sticking against the tissue and / or itself when being retracted from the deployed configuration back to the furled, stowed configuration for removal.

[0096] Preferably, the drive elements 430, 438 are counterrotated until the flexible substrate 422 is deployed and the electrode 424 is in proper position relative to the tissue 462. In some embodiments, the electrode 424 may be in contact with the tissue 462, while in other embodiments, the electrode 424 may be adjacent, but not incontact, with the tissue 462. In the fully expanded position, the flexible substrate 422 may have an outer diameter of approximately 32 mm in some embodiments. In other embodiments, the flexible substrate 422 may have an outer diameter ranging from approximately 8 mm to 45 mm in the fully expanded position. 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 expanded as desired and that the electrode 424 is in proper position.

[0097] Once the flexible substrate 422 is in the expanded position, the electrode 424 may be energized to ablate target cells within the tissue 462 as described previously. Once the ablation treatment at the tissue site has been completed, the drive elements 430, 438 may be counterrotated to urge the furled sections 454, 456 to wrap in an overlapping manner against the respective drive elements 430, 438 for retracting the flexible substrate 422 from the expanded position back to the stowed position. Once the flexible substrate 422 is wrapped into the two furled sections 454, 456 into the stowed 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 stowed position, where the first furled section 454 is received within the first seat 414 and the second furled section 456 is received within the second seat 416.

[0098] In some embodiments, counterrotation of the drive elements 430, 438 allows the electrode 424 to be deployed and retracted without applying torque to the target tissue. Accordingly, the design of the electrode treatment system 400 described herein allows the tissue to remain in a neutral position during delivery, treatment, and retraction of the electrode treatment system 400.

[0099] In some embodiments, when the flexible substrate 422 has been moved distally relative to the housing 404, the drive elements 430, 438 may be further actuatable via the drives 434, 442, respectively, to adjust a lateral position of the flexible substrate 422. For example, in some embodiments, the flexible substrate 422 may be off-center relative to the lumen of the tissue 462 such that the electrode 424 may not properly reach all the targeted tissue when the flexible substrate 422 is deployed. Accordingly, the drive elements 430, 438 may be used to adjust a lateral position of the flexible substrate 422, either prior and / or after deployment, to essentially re-center or otherwise position the flexible substrate 422 to ensure the electrode 424 is properly positioned upon deployment for delivering effectivetreatment. For example, one drive element may be driven to rotate and / or counterrotate more than the other drive element to adjust the lateral position of the flexible substrate 422 and thus the electrode 424 accordingly.

[0100] As described above in the embodiment illustrated in FIGS. 4-7, the drive system 428 may include separate drives 434, 442 for actuating the drive elements 430, 438 independently of one another. Accordingly, in some embodiments, the drive elements 430, 438 may move independently of one another and / or in a coordinated fashion to simultaneously deploy the flexible substrate 422 as described above. In other embodiments, the drive elements 430, 438 may be driven entirely independently from another but not in a coordinated fashion such that a rate and / or amount of unfurling of the first furled section 454 may be different as compared to the second furled section 456 based on independent control of the drive elements 430, 438. The ability to independently control deployment of the furled sections 454, 456 may be beneficial to help ensure that the flexible substrate 422 is deployed as needed given characteristics and features of the target tissue site.

[0101] In yet another embodiment, the electrode treatment system 400 may be configured in a generally similar fashion as described above but may rely on rotation of only one of the drive elements 430, 438 to deploy and retract the flexible substrate 422. For example, the electrode treatment system 400 may include the first drive element 430 and the second drive element 438 coupled to the flexible substrate 422 in a similar fashion as described above with reference to FIGS. 4-7. In one example embodiment, the drive 434 may be operable to rotate the first drive element 430 about a rotational axis, while the second drive element 438 is non-rotatable relative to the first drive element 430 (or vice versa). In this embodiment, the drives 434, 442 are operable to axially move the drive elements 430, 438 distally of the housing 404, where rotation of the first drive element 430 about the rotational axis unfurls both the first furled section 454 from the first drive element 430 and the second furled section 456 from the second drive element 438 to deploy the flexible substrate 422 from the stowed position into the expanded position. Since the second drive element 438 is non- rotatable in this configuration and supports the second furled section 456, in some embodiments, rotation of the first drive element 430 may urge the first furled section 454 to unfurl first (either partially or entirely) before the second furled section 456 unfurls. In some embodiments, the drive 434 is operable to rotate the first drive element 430 in a first rotational direction about the rotational axis to deploy the flexiblesubstrate 422 from the stowed position into the expanded position as described above. Once treatment has been completed, the drive 434 is further operable to rotate the first drive element 430 in a second rotational direction opposite the first rotational direction to retract the flexible substrate 422 from the expanded position to the stowed position. Thereafter, the drives 434, 442 axially retract the drive elements 430, 438 to return the flexible substrate 422 to the housing 404.

[0102] While not explicitly described herein, it should be understood that many of the same features and characteristics of the electrode treatment system 400 described above using independently actuatable drive elements 430, 438 applies equally to the configuration of the electrode treatment system 400 described in the preceding paragraph where only one of the drive elements 430, 438 is rotatable and the other is non-rotatable or otherwise fixed rotatably. Accordingly, to avoid repetition, those features are not further described herein with the understanding that the embodiments may be combined in a suitable fashion.

[0103] As described with reference to FIGS. 4-7, arranging the flexible substrate 422 into a dual-wrapped configuration including the furled sections 454, 456 reduces an overall profile of the rolled flexible substrate 422 when in the stowed position as compared to a configuration using a singular wrapped flexible substrate about a single axis. In addition, this compact design for the flexible substrate 422 is achieved while maintaining the overall dimensions of the flexible substrate 422 when in an expanded position sufficiently large to support a suitable electrode 424 for treatment purposes as described above. In some embodiments, the flexible substrate 422 may have an outer diameter in the expanded position that ranges between 3:1 and 6:1 as compared to a respective outer diameter of each of the first furled section 454 and the second furled section 466 when the flexible substrate 422 is in the stowed position. This design allows for the flexible substrate 422 to be packaged in a typical duodenoscope or other suitable instrument without the need to sacrifice other typical features and functions of the duodenoscope, such as a camera, lighting, suction, irrigation, and the like.

[0104] In some embodiments, the electrode treatment system 400 may further include a support structure 464 for the housing 404 and the working channel 410 as illustrated in FIG. 8. In some embodiments, the support structure 464 may support the flexible substrate 422, the sheath 460, and the distal portions 436, 444 of the drive elements 430, 438 as arranged in a similar fashion illustrated in FIGS. 4-7. Thesupport structure 464 may also impart additional rigidity along the distal portion 408 of the elongate flexible member 402.

[0105] FIG. 9 illustrates another example of an electrode treatment system 900 for delivering a flexible substrate 908 with an electrode (not shown) to a target region, the electrode treatment system 900 including a gear system 912 for controlling operation of the drive elements 902, 904 coupled to the flexible substrate 908. Generally, the electrode treatment system 900 may have the same or substantially similar features as the electrode treatment system 400 described previously with reference to FIGS. 4-7. Accordingly, certain details of the electrode treatment system 900 may not be further described in detail below to avoid repetition and / or obscuring more pertinent details of the embodiment. Briefly, with reference to FIG. 9, the electrode treatment system 900 includes a first drive element 902 and a second drive element 904 extending into a housing 906, where the drive elements 902, 904 are coupled to a flexible substrate 908 and actuatable via a drive system 910 to deploy the flexible substrate 908 in a generally similar fashion as described previously with respect to electrode treatment system 400. The following provides additional details of features incorporated with the electrode treatment system 900, particularly the gear system 912.

[0106] With reference to FIG. 9, in some embodiments, the electrode treatment system 900 includes a gear system 912 coupling the first drive element 902 and the second drive element 904 to one another. The gear system 912 essentially allows one of the drive elements 902, 904 to be rotated by the drive system 910, where 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 may rotate the first drive element 902 about a first rotational axis and the gear system 912 may in turn rotate the second drive element 904 about a second rotational axis spaced apart from the first rotational axis. In a similar fashion as described above with reference to FIG. 4, the first drive element 902 may rotate in a first direction and the second drive element 904 may rotate in an opposite second direction via the gear system 912 such that the drive elements 902, 904 are counterrotated relative to one another. As described previously with reference to FIG. 4, counterrotation of the drive elements 902, 904 adjusts the flexible substrate 908 from the stowed position to an expanded position for treatment. Thereafter, the drive elements 902, 904 may be counterrotated to adjustthe flexible substrate 908 back from the expanded position to the stowed position upon completion of treatment for retraction and removal.

[0107] FIG. 10 illustrates yet another example of an electrode treatment system 1000 for delivering a flexible substrate 1008 with an electrode 1012 to a target region. Generally, the electrode treatment system 1000 may have the same or substantially similar features as the electrode treatment system 400 described previously with reference to FIGS. 4-7. Accordingly, certain details of the electrode treatment system 1000 may not be further described in detail below to avoid repetition and / or obscuring more pertinent details of the embodiment. Briefly, with reference to FIG. 10, the electrode treatment system 1000 includes a first drive element 1002 and a second drive element 1004 extending into a housing 1006, where the drive elements 1002, 1004 are coupled to a flexible substrate 1008 and actuatable via a drive system 1010 to deploy the flexible substrate 1008 in a similar fashion as described previously with respect to electrode treatment system 400.

[0108] With reference to FIG. 10, the flexible substrate 1008 may be coupled to the drive elements 1002, 1004 in a similar dual-wrapped configuration as described previously with reference to FIG. 4. As illustrated in FIG. 10, in some embodiments, the flexible substrate 1008 may comprise multiple, longitudinally spaced-apart segments 1008a, 1008b, 1008c, where the multiple 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 one another. Accordingly, in some embodiments, the segments 1008a, 1008b, 1008c may each include wiring, circuitry, and other electronics (not shown) arranged to independently power the electrodes 1012 supported thereon relative to one another. In other embodiments, the segments 1008a, 1008b, 1008c may include shared wiring, circuitry, and other electronics (not shown) and may be electrically coupled with one another and work in tandem as essentially a multisegmented, flexible substrate 1008. In either configuration, the electrode treatment system 1000 is designed to simplify treatment by increasing the overall region of tissue that may be treatable with a single deployment of the flexible substrate 1008, thereby reducing overall treatment time and minimizing potential tissue damage that may be caused when repositioning the electrode treatment system 1000 for subsequent treatments. For example, as illustrated in FIG. 10, the segments 1008a, 1008b, 1008c are deployed against the tissue lumen 1014 to collectively treat a tissue region thatmay be approximately three times larger as compared to using a single flexible substrate 1008 (see FIG. 7 for example).

[0109] In one embodiment, each segment 1008a, 1008b, 1008c of the flexible substrate 1008 may be rolled into three pairs of furled sections (not shown) in a similar fashion as described previously with reference to FIGS. 4-7. In this configuration, one set of furled sections from each of the three pairs may be coupled to the first drive element 1002 and the second set of furled sections from each of the three pairs may be coupled to the second drive element 1004, where the drive elements 1002, 1004 are operable to deploy and retract the flexible substrate 1008 in a similar fashion as described previously. The three pairs of furled sections may be housed within the sheath 1016 disposed within the housing 1006 to retain their rolled configuration when in the stowed position.

[0110] FIG. 11 illustrates another example of an electrode treatment system 1100 for delivering a flexible substrate 1108 with an electrode 1110 to a target region for treatment. Generally, the electrode treatment system 1100 may have the same or substantially similar features as the electrode treatment system 400 described previously with reference to FIGS. 4-7. Accordingly, certain details of the electrode treatment system 1100 may not be further described in detail below to avoid repetition and / or obscuring more pertinent details of the embodiment. Briefly, with reference to FIG. 11 , the electrode treatment system 1100 includes a first drive element 1102 and a second drive element 1104 extending into a housing 1106, where the drive elements 1102, 1104 are coupled to a flexible substrate 1108 with an electrode 1100 and actuatable via a drive system 1112 to deploy the flexible substrate 1108 in a similar fashion as described previously with respect to electrode treatment system 400.

[0111] With reference to FIG. 11 , in some embodiments, the electrode treatment system 1100 further includes an expansion member 1114 coupled to the elongate flexible member 1116, where the expansion member 1114 is radially expandable relative to the elongate flexible member 1116. The expansion member 1114 may be expanded in a variety of different manners. For example, in some embodiments, the expansion member 1114 may be inflated with a fluid, such as air, saline, a radiopaque solution, and the like. In some embodiments, the fluid may be introduced to the expansion member 1114 through a lumen (not shown) of the elongate flexible member 1116. The expansion member 1114 may have a length of approximately 4 cm in an unexpanded configuration and may inflate to a diameter between 1 cm and 4 cm. Inother embodiments, the length and inflatable diameter of the expansion member 1114 may vary depending on the characteristics and dimensions of the target site for tissue treatment. In other examples, the expansion member 1114 may be expanded in other suitable ways (e.g., rolling, unfurling, pushing). In the illustrated embodiment, the expansion member 1114 is illustrated as an inflatable balloon. In some embodiments, the balloon may be a compliant balloon made of polyurethane, silicone, or other suitable material designed to inflate several times its nominal size. In other embodiments, the balloon may be a semi-compliant balloon made of polyurethane or other suitable material designed for less expansion as compared to a compliant balloon. In other embodiments, other expansion members, such as braided meshes, expandable frames, and the like, may be used.

[0112] In some embodiments, the expansion member 1114 may be housed within the housing 1106 and configured to extend through a first working channel 1118 extending through the elongate flexible member 1116, the first working channel 1118 having an opening on a distal face 1120 of the housing 1106. In this embodiment, the flexible substrate 1108 may be arranged in a dual-wrapped configuration as previously described, where the flexible substrate 1108 is arranged within a second working channel 1122 having an opening on the distal face 1120 of the housing 1106, where the first working channel 1118 and the second working channel 1122 are offset from one another on the distal face 1120. For example, in one embodiment, the first working channel 1118 may be vertically offset (e.g., positioned above) from the second working channel 1122. In some embodiments, the working channels 1118, 1122 may be aligned along a vertical axis extending through the distal face 1120 of the housing 1106.

[0113] In this configuration, the expansion member 1114 is axially movable relative to the housing 1106 and extendable distally thereto through the first working channel 1118 to engage the flexible substrate 1108 after it has been unfurled into a first expanded position via rotation of one or both of the drive elements 1102, 1104 in a similar fashion as described above in any of the embodiments with reference to FIGS. 4-10. Once the flexible substrate 1108 is in the first expanded position, the expansion member 1114 extends distally through the first working channel 1118 and thereafter radially expands to further expand the flexible substrate 1108 from the first expanded position to a second expanded position. Expansion of the expansion member 1114 exerts radial forces against the flexible substrate 1108, which urge the flexiblesubstrate 1108 to further unfurl and / or expand to the second expanded position toward the tissue 1124 at the treatment site. As the flexible substrate 1108 deploys to the second expanded position, the electrode 1110 is moved into position adjacent (or in contact with) the tissue 1124. In some embodiments, a rate and / or degree of expansion of the expansion member 1114 may be controlled to ensure that the electrode 1110 appropriately contacts (or is otherwise positioned with sufficient proximity) for treatment of the tissue 1124 while avoiding over-expansion of the flexible substrate 1108 that may result in tissue damage. With the electrode 1110 in proper position, a current may be run through the electrode 1110 to generate an electric field for electroporation and / or electrolysis as described previously for tissue ablation. Upon completion of treatment, the expansion member 1114 may be deflated and retracted back into the first working channel 1118. Thereafter, the flexible substrate 1108 may be retracted into the stowed position via rotation of one or both of the drive elements 1102, 1104 to move the electrode 1110 away from the tissue 1124 and facilitate removal of the electrode treatment system 1100.

[0114] As described, the expansion member 1114 may support the flexible substrate 1108 to ensure it unfurls and / or expands as completely as needed so the electrode 1110 is in a viable position for treatment purposes. Accordingly, the flexible substrate 1108 may unfurl to a first expanded position via rotation of the drive elements 1102, 1104 as described, and the expansion member 1114 may urge the flexible substrate 1108 to expand to a second expanded position thereafter, such that the outer diameter of the flexible substrate 1108 is larger in the second expanded position as compared to the outer diameter of the flexible substrate 1108 in the first expanded position to ensure the electrode 1110 is in proper position against (or adjacent) the tissue 1124 for treatment.

[0115] As noted previously, in some embodiments, the electrode treatment system 1100 may be repositioned (e.g., advanced or retracted relative to a first tissue treatment site) to a different region and the process repeated as needed to sequentially treat a larger region of tissue. In some embodiments, the flexible substrate 1108 and expansion member 1114 may be readjusted to the second tissue treatment site in the fully deployed configuration (such as that shown in FIG. 11 ) to expedite treatment. In other embodiments, the expansion member 1114 may instead be partially or entirely deflated and the flexible substrate 1108 may also be partially or entirely retracted to move the electrode treatment system 1100 to the second tissuetreatment site. Retracting one or both of these components prior to moving the electrode treatment system 1100 may facilitate repositioning of the electrode treatment system 1100 by decreasing its overall profile and may also reduce the risk of inadvertent injury caused by the electrode treatment system 1100 to any surrounding tissue during movement.

[0116] It should be understood that example embodiments provided herein of both the design of catheter delivery systems and the potential clinical applications associated therewith are not intended to be limiting. Many other configurations of delivery systems exist, as well as applications that would benefit from the use of the disclosed subject matter. In addition, it is to be appreciated that any one of the above embodiments or processes, or specific features associated therewith, may be combined with one or more other embodiments and / or processes or be separated and / or performed amongst separate devices or device portions in accordance with the present systems, devices, and methods.

[0117] Finally, the disclosure is intended to be merely illustrative of the present devices, apparatuses, systems, and methods and should not be construed as limiting the appended claims to any particular embodiment or group of embodiments. Thus, while the present disclosure has been described in particular detail with reference to exemplary embodiments, it should also be appreciated that numerous modifications and alternative embodiments may be practiced without departing from the broader and intended spirit and scope of the present disclosure as set forth in the claims that follow. Accordingly, the specification and drawings are to be regarded in an illustrative manner and are not intended to limit the scope of the appended claims.

Claims

CLAIMS1 . An electrode treatment system, the system comprising: a housing; 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 including an electrode disposed thereon, 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 stowed position, a first furled section of the flexible substrate encircles the distal portion of the first drive element and a second furled section of the flexible substrate encircles the distal portion of the second drive element, the first furled section and the second furled section laterally offset from one another within the housing.

2. The system of claim 1 , wherein counterrotation of the first drive element and the second drive element relative to one another unfurls the first furled section from the first drive element and the second furled section from the second drive element to deploy the flexible substrate from the stowed position to an expanded position.

3. The system of claim 1 , wherein the first furled section and the second furled section are wrapped in opposite directions relative to one another around the respective first drive element and the second drive element.

4. The system of claim 1 , the housing further including a working channel with an opening on a distal face of the housing, the working channel including a first seat receiving the first furled section of the flexible substrate and a second seat receiving the second furled section of the flexible substrate when the flexible substrate is in the stowed position.

5. The system of claim 1 , the housing further including a working channel with an opening on a distal face of the housing, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first furled sectionand the second furled section, respectively, through the opening of the working channel and distally of the housing.

6. The system of claim 5, wherein the first drive element and the second drive element are actuatable to deploy the flexible substrate from the stowed position to an expanded position when the first furled section and the second furled section are positioned distally of the housing.

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

8. The system of claim 7, the housing further including a working channel with an opening on a distal face 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 furled section and the second furled section, respectively, through the sheath and the opening of the working channel and distally of the housing.

10. The system of claim 9, wherein the first drive element and the second drive element are actuatable to deploy the flexible substrate from the stowed position to an expanded position when the first furled section and the second furled section are positioned distally of the housing.11 . The system of claim 1 , wherein the first drive element and the second drive element are actuatable independently from one another such that the first drive element drives the first furled section of the flexible substrate and the second drive element drives the second furled section of the flexible substrate independently from one another between the stowed position and an expanded position.

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 from one another.

13. The system of claim 1 , further comprising: a drive system coupled to one of the first drive element and the second drive element, the drive system operable to rotate the one of the first drive element and the second drive element in a first direction; and a gear system coupling the first drive element and the second drive element to one another, wherein the gear system rotates the other of the first drive element and the second drive element in a second direction opposite the first direction.

14. The system of claim 1 , wherein the flexible substrate has an outer diameter in an expanded position that ranges between 3:1 and 6:1 as compared to a respective outer diameter of each of the first furled section and the second furled section when the flexible substrate is in the stowed position.

15. The system of claim 1 , wherein the first drive element and the second drive element are further rotatable to retract the flexible substrate from an expanded position to the stowed position.

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

17. An electrode treatment system, the system comprising: a housing; a first drive element rotatable about a rotational axis, the first drive element including a proximal portion and an opposite distal portion, wherein the distal portion extends into the housing; a second drive element including a proximal portion and a distal portion, wherein the distal portion extends into the housing; anda flexible substrate including an electrode disposed thereon, 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 stowed position, a first furled section of the flexible substrate encircles the distal portion of the first drive element and a second furled section of the flexible substrate encircles the distal portion of the second drive element, the first furled section and the second furled section laterally offset from one another within the housing, and wherein rotation of the first drive element about the rotational axis unfurls both the first furled section from the first drive element and the second furled section from the second drive element to deploy the flexible substrate from the stowed position into an expanded position.

18. The system of claim 17, wherein the second drive element is non-rotatable relative to the first drive element.

19. The system of claim 17, wherein the first drive element is coupled to a drive system operable to rotate the first drive element about the rotational axis in a first rotational direction to deploy the flexible substrate from the stowed position into the expanded position.

20. The system of claim 19, where the drive system is further operable to rotate the first drive element about the rotational axis in a second rotational direction opposite the first rotational direction to retract the flexible substrate from the expanded position to the stowed position.

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

22. The system of claim 17, wherein the first furled section and the second furled section are wrapped in opposite directions relative to one another around the respective first drive element and the second drive element.

23. The system of claim 17, the housing further including a working channel with an opening on a distal face of the housing, the working channel including a first seat receiving the first furled section of the flexible substrate and a second seat receiving the second furled section of the flexible when the flexible substrate is in the stowed position.

24. The system of claim 17, the housing further including a working channel with an opening on a distal face of the housing, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first furled section and the second furled section, respectively, through the opening of the working channel and distally of the housing.

25. The system of claim 24, wherein the first drive element is actuatable to deploy both the first furled section and the second furled section of the flexible substrate from the stowed position to the expanded position when the first furled section and the second furled section are positioned distally of the housing.

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

27. The system of claim 26, the housing further including a working channel with an opening on a distal face 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 furled section and the second furled section, respectively, through the sheath and the opening of the working channel and distally of the housing.

29. The system of claim 28, wherein the first drive element is actuatable to deploy both the first furled section and the second furled section of the flexible substrate fromthe stowed position to the expanded position when the first furled section and the second furled section are positioned distally of the housing.

30. The system of claim 17, wherein the flexible substrate has an outer diameter in the expanded position that ranges between 3:1 and 6:1 as compared to a respective outer diameter of each of the first furled section and the second furled section when the flexible substrate is in the stowed position.

31. The system of claim 17, the housing further including a first working channel with a first opening on a distal face of the housing, the system further comprising an expansion member extendable distally of the housing along the distal face thereof and through the first opening of the first working channel, the expansion member engaging the flexible substrate when in the expanded position, wherein the expansion member is radially expandable to further expand the flexible substrate from the expanded position to a second expanded position.

32. The system of claim 31 , the housing further including a second working channel with a second opening on the distal face of the housing, the second opening offset from the first opening of the first working channel, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first furled section and the second furled section, respectively, through the second opening of the second working channel and distally of the housing.

33. An electrode treatment system, the system comprising: a housing; 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 including an electrode disposed thereon, 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 stowed position, a first furled section of the flexible substrate encircles the distal portion of the first drive element and a second furled section of the flexible substrate encircles the distal portion of the second drive element,the first furled section and the second furled section laterally offset from one another within the housing, and wherein rotation of one or both of the first drive element and the second drive element unfurls the first furled section from the first drive element and the second furled section from the second drive element to deploy the flexible substrate from the stowed position into a first expanded position; and an expansion member engaging the flexible substrate when in the first expanded position, wherein the expansion member is radially expandable to further expand the flexible substrate from the first expanded position to a second expanded position.

34. The system of claim 33, the housing including a first working channel with a first opening on a distal face of the housing, wherein the expansion member is axially movable relative to the housing and extendable distally thereto through the first opening of the first working channel.

35. The system of claim 34, the housing further including a second working channel with a second opening on the distal face of the housing, wherein the first drive element and the second drive element are axially movable relative to the housing to drive the first furled section and the second furled section of the flexible substrate, respectively, through the second opening of the second working channel and distally 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 face of the housing.

37. The system of claim 33, the housing further including a working channel with an opening on a distal face of the housing, the working channel including a first seat receiving the first furled section of the flexible substrate and a second seat receiving the second furled section of the flexible when the flexible substrate is in the stowed position.

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

39. The system of claim 38, the housing further including a working channel with an opening on a distal face 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 furled section and the second furled section, respectively, through the sheath and the opening of the working channel and distally of the housing.

41. The system of claim 33, wherein counterrotation of the first drive element relative to the second drive element simultaneously unfurls the first furled section from the first drive element and the second furled section from the second drive element.

42. The system of claim 41 , wherein the first furled section and the second furled section are wrapped in opposite directions around the respective first drive element and the second drive element.

43. The system of claim 33, wherein the first drive element and the second drive element are actuatable independently relative to one another such that the first drive element drives the first furled section of the flexible substrate and the second drive element drives the second furled section of the flexible substrate independently from one another between the stowed position and the first expanded position.

44. The system of claim 33, wherein after deployment of the flexible substrate to the second expanded position, further rotation of the one or both of the first drive element and the second drive element retracts the flexible substrate from the second expanded position to the stowed 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 operable to rotate the one of the first drive element and the second drive element in a first direction; and a gear system coupling the first drive element and the second drive element to one another, wherein the gear system rotates the other of the first drive element and the second drive element in a second direction opposite the first direction.

46. The system of claim 33, wherein one of the first drive element and the second drive element is non-rotatable relative to the other of the first drive element and the second drive element.

47. The system of claim 33, wherein the flexible substrate has an outer diameter in the first expanded position that ranges between 3:1 and 6:1 as compared to a respective outer diameter of each of the first furled section and the second furled section when the flexible substrate is in the stowed position.

48. The system of claim 47, wherein the outer diameter of the flexible substrate is larger in the second expanded position as compared to the first expanded position.

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