Devices, systems, and methods for pulsed electric field treatment of the duodenum

Abstract

Described herein are devices, systems, and methods for applying pulsed or modulated electric fields to tissue. In some variations, the devices may include a first elongate body having a lumen, a second elongate body positioned at least partially within the lumen, and an expandable member wrapped around the second elongate body. The expandable member may have an inner end coupled to the second elongate body, an outer end coupled to the first elongate body, and an electrode array.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 62 / 924,100, filed October 21, 2019, and U.S. Provisional Application No. 63 / 029,275, filed May 22, 2020, the contents of each of which are incorporated herein by reference in their entirety.

[0002] The devices, systems, and methods herein relate to applying pulsed electric fields to tissue to treat chronic diseases, including, but not limited to, diabetes. [Background technology]

[0003] Diabetes is a widespread condition affecting millions of people worldwide. In the United States alone, it is estimated that over 20 million people have the condition. Diabetes accounts for hundreds of billions of dollars annually in direct and indirect medical costs. Depending on the type (e.g., type 1, type 2), diabetes can be associated with one or more symptoms such as fatigue, blurred vision, and unexplained weight loss, and can be further associated with one or more complications such as hypoglycemia, hyperglycemia, ketoacidosis, neuropathy, and nephropathy.

[0004] Duodenal resurfacing has been proposed as a treatment for chronic diseases such as obesity and diabetes. For example, removing a large portion of the mucosal cells from the portion of the large intestine closest to the stomach may regenerate a rejuvenated mucosal layer, thereby restoring healthy (non-diabetic) signaling. Conventional treatments that apply thermal energy to the duodenum risk excessive heating and therefore damage to more layers of the duodenum (e.g., the muscularis fascia) and / or require compensation for this excessive heating. Conversely, conventional solutions may produce incomplete and / or uneven treatment. Therefore, additional systems, devices, and methods for treating duodenal tissue may be desirable. Summary of the Invention [Means for solving the problem]

[0005] Described herein are devices, systems, and methods for applying pulsed or modulated electric fields to tissue. These systems, devices, and methods can treat a patient's duodenal tissue, for example, to treat diabetes. Additionally, the systems and devices may provide temperature feedback and procedural visualization. In some variations, the device may include a first elongate body having a lumen, a second elongate body positioned at least partially within the lumen, and an expandable member wrapped around the second elongate body. The expandable member may have an inner end coupled to the second elongate body, an outer end coupled to the first elongate body, and an electrode array.

[0006] In some variations, the expandable member may include multiple turns around the second elongate body. In some variations, a connector may couple the first elongate body to an outer end of the expandable member. In some variations, the second elongate body may be configured to rotate relative to the first elongate body to transition the expandable member between the rolled configuration and the deployed configuration. In some of these variations, the expandable member may comprise a lumen having a diameter of at least 10 mm in the deployed configuration.

[0007] In some of these variations, a system including the device may further include a third elongate body disposed within the lumen of the expandable member. In some of these variations, the third elongate body may include an endoscope.

[0008] In some variations, the device may further include a distal dilator and a proximal dilator coupled to one of the first elongate body and the second elongate body, and the expandable member can be disposed between the distal dilator and the proximal dilator.

[0009] In some variations, the device may further include one or more of a gear and a friction roller coupled to the second elongate body. The expandable member may include a track configured to couple to the one or more gears and friction rollers. In some of these variations, the track may include a plurality of spaced-apart openings in the expandable member. In some variations, the expandable member may include one or more fluid openings. In some variations, the expandable member may include one or more fluid pathways.

[0010] In some variations, a signal generator can be coupled to the electrode array and configured to generate a pulsed or modulated electric field waveform having a frequency of about 250 kHz to about 950 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A per square centimeter of tissue.

[0011] In some variations, the signal generator can be configured to inhibit delivery of the pulse waveform based on tissue temperature. In some variations, the electrode array can be configured to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. In some variations, the expandable member can include a temperature sensor having a serpentine shape. In some variations, the expandable member can define one or more openings therethrough. In some variations, the electrode array can be configured to generate a therapeutic electric field that treats a predetermined set of cell types but not muscle tissue. In some variations, the electrode array can be configured to generate a therapeutic electric field that treats cells but leaves the tissue scaffold intact.

[0012] Also described herein are devices that include an elongate body and a plurality of elongate electrodes coupled to the elongate body. The plurality of elongate electrodes can have a ratio of center-to-center distance between adjacent electrodes to electrode width of about 2.3:1 to about 3.3:1. In some variations, the plurality of elongate electrodes has a center-to-center distance between adjacent electrodes of less than about 5 mm.

[0013] In some variations, a signal generator can be coupled to the plurality of electrodes and configured to generate a pulsed or modulated electric field waveform having a frequency of about 250 kHz to about 950 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A per square centimeter of tissue.

[0014] In some variations, the expandable member may be coupled to the elongate body and may include a plurality of electrodes. The expandable member may have a compressed configuration and an expanded configuration. In the expanded configuration, the expandable member may include a lumen. A second elongate body may be disposed within the lumen of the expandable member. The second elongate body may include an endoscope.

[0015] In some variations, the proximal and distal portions of the expandable member may be transparent. In some variations, a second expandable member may be coupled to the elongate body. In some of these variations, the second expandable member may be inflatable.

[0016] In some variations, the plurality of elongated electrodes may comprise a first electrode and a second electrode parallel to the first electrode. In some variations, the plurality of elongated electrodes may comprise the first electrode and the second electrode in an interdigitated configuration. In some variations, the center-to-center distance between adjacent electrodes and the width of the plurality of elongated electrodes may be substantially equal. In some variations, the plurality of elongated electrodes comprises a center-to-center distance between adjacent electrodes of less than about 5 mm.

[0017] In some variations, a tissue contacting layer may be disposed on the elongate electrode. The tissue contacting layer may have a lower electrical conductivity than the electrical conductivity of the elongate electrode.

[0018] In some variations, the electrical conductivity of the tissue contacting layer may be about 0.03 S / m to about 0.9 S / m. For example, the electrical conductivity of the tissue contacting layer may be about 0.03 S / m to about 0.6 S / m, or about 0.03 S / m to about 0.3 S / m. In some variations, the tissue contacting layer may have a thickness of about 10% to about 20% of the width of the electrode. In some variations, at least one of the electrodes may have a semi-elliptical cross-sectional shape. In some variations, the ratio of the electrode height to the electrode width is about 1:4 to about 1:8. In some variations, adjacent electrodes may be spaced apart by a weighted average distance of about 0.3 mm to about 6 mm. In some variations, a hydrophilic layer may be disposed on the plurality of electrodes. In some variations, a conductive layer may be disposed on the plurality of electrodes. The conductive layer may comprise one or more of a polymer and a conductive medium, such as graphite, silver, or a metal. In some variations, the conductive layer may be a coating. In some variations, the surface area of ​​the plurality of electrodes can comprise between about 20% and about 45% of the surface area of ​​the expandable member in a given configuration (eg, the expanded configuration).

[0019] In some variations, a fluid source may be in fluid communication with the expandable member. In some variations, one or more of the plurality of elongate electrodes may include a fluid opening. In some variations, one or more of the plurality of elongate electrodes may include one or more fluid pathways. In some variations, a fluid source may be in fluid communication with the plurality of elongate electrodes.

[0020] In some variations, the system of devices may include a fluid source in fluid communication with the expandable member and one or more of the plurality of elongated electrodes. In some variations, one or more of the plurality of elongated electrodes may include a fluid opening. In some variations, one or more of the plurality of elongated electrodes may include one or more fluid pathways. In some variations, the center-to-center distance between adjacent electrodes of the plurality of elongated electrodes may be less than about 5 mm.

[0021] Also described herein are devices comprising an elongate body and an expandable member coupled to the elongate body. The expandable member may comprise a lumen formed by coupling an outer surface of the expandable member to an inner surface of the expandable member and a plurality of elongate recesses. A plurality of electrodes may be coupled to the expandable member.

[0022] In some variations, the expandable member can be concentrically coupled to the elongate body. In some variations, the elongate body can be coupled to a sidewall of the expandable member. In some variations, a second expandable member can be coupled to the elongate body and disposed distally of the expandable member. In some variations, at least the proximal and distal ends of the second expandable member can be transparent. In some variations, the second elongate body can be disposed within a lumen of the expandable member. In some variations, the plurality of electrodes comprises a plurality of parallel elongate electrodes. In some variations, the plurality of electrodes can comprise a plurality of interdigitated electrodes.

[0023] In some variations, the system may include an elongate body and an expandable member coupled to the elongate body. The elongate body includes a lumen, a compressed configuration, and an expanded configuration. The expandable member includes an electrode array. The lumen of the expandable member can be configured to releasably couple to a visualization device. In some variations, the lumen defines a central longitudinal axis of the expandable member. In some variations, the expandable member may include a fluid opening. In some variations, the expandable member may include one or more fluid pathways.

[0024] Also described herein is a system comprising an elongate body and an expandable member coupled to the elongate body, the expandable member having a compressed configuration and an expanded configuration. The expandable member may further comprise an electrode array comprising a plurality of electrodes and a signal generator coupled to the electrode array. The signal generator may be configured to deliver a pulsed or modulated electric field waveform to the electrode array to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm.

[0025] Also described herein is a system comprising an elongate body and an expandable member coupled to the elongate body and comprising a lumen, a compressed configuration, and an expanded configuration. The expandable member may comprise an electrode array. The lumen of the expandable member may be configured to releasably receive a visualization device.

[0026] In some variations, the lumen can define a central longitudinal axis of the expandable member. In some variations, the expandable member can include one or more openings extending therethrough. In some variations, the visualization device can be configured to aspirate tissue through the one or more openings at a pressure of about 10 mmHg to about 200 mmHg.

[0027] Also described herein are systems that include an elongate body and an expandable member coupled to the elongate body, the expandable member comprising a lumen, a compressed configuration, and an expanded configuration. The expandable member may comprise an electrode array. A visualization device can be configured to releasably couple to the lumen of the expandable member. In some variations, the visualization device comprises an aspiration lumen. In some variations, the visualization device comprises an irrigation lumen.

[0028] Also described herein is a method of treating diabetes that includes advancing a pulsed electric field device into a patient's duodenum. The pulsed electric field device may include an elongate body and an expandable member coupled to the elongate body. The expandable member may include an electrode array. A pulsed waveform may be delivered to the electrode array to generate a pulsed or modulated electric field, thereby treating the duodenum.

[0029] In some variations, the electrode array may comprise a plurality of spaced apart electrodes forming parallel lines and / or an interdigitated configuration. In some of these variations, adjacent parallel lines of the electrode array may be configured with alternating polarity. In some variations, the plurality of electrodes may comprise a plurality of interdigitated electrodes. In some variations, the pulsed or modulated electric field may vary spatially by up to about 20% at a given treatment distance from the electrode array.

[0030] In some variations, the expandable member may include a lumen therethrough, and the method may further include advancing an endoscope through the lumen of the expandable member. In some variations, the endoscope may be retracted to view the duodenal tissue proximal to the expandable member. In some variations, each of the plurality of electrodes may be an elongated electrode. In some variations, each of the plurality of electrodes may be a semi-elliptical electrode. In some variations, the temperature of the expandable member may be measured during delivery of the pulsed waveform. In some variations, delivery of the pulsed waveform may be inhibited based on the measured temperature. In some variations, the pulsed or modulated electric field may be a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. In some variations, the tissue may be drawn into the expandable member at a pressure of about 10 mmHg to about 200 mmHg. In some variations, fluid may be output between the pulsed electric field device and the duodenum from the expandable member.

[0031] Also described herein is a method for treating diabetes, including advancing a pulsed electric field device toward a first portion of a patient's duodenum. The pulsed electric field device can include an expandable member with an electrode array. The expandable member can be transitioned to an expanded configuration. A first pulse waveform can be delivered to the electrode array to generate a first pulsed electric field or a first modulated electric field, thereby treating the first portion. The pulsed electric field device can be advanced toward a second portion of the duodenum. A second pulse waveform can be delivered to the electrode array to generate a second pulsed electric field, thereby treating the second portion.

[0032] In some variations, the expandable member may include a temperature sensor. The temperature of the tissue may be measured using the temperature sensor. Delivery of the pulse waveform may be modulated (e.g., inhibited) based on one or more of the measured temperature and the rate of temperature change. In some variations, the expandable member may be deployed to transition the expandable member to the expanded configuration. In some variations, the expandable member may include a lumen having a first diameter in the compressed configuration and a second diameter in the expanded configuration. The second diameter may be smaller than the first diameter. A third elongate body may be advanced through the lumen in the expanded configuration.

[0033] In some variations, the expandable member may include a second expandable member disposed distally of the expandable member. The second expandable member may be inflated. In some variations, deploying the expandable member includes deploying one or more turns of the expandable member. In some variations, the first and second pulse waveforms include a frequency of about 250 kHz to about 950 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A or about 0.6 A to about 65 A per square centimeter of tissue. For example, the current density may be about 0.6 A to about 13 A per square centimeter of tissue from the electrode array. In some variations, fluid may be output between the pulsed electric field device and the duodenum from the expandable member.

[0034] In some variations, one or more of the first pulsed or modulated electric field and the second pulsed or modulated electric field can be a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm.

[0035] In some variations, tissue may be drawn into the expandable member during delivery of one or more of the first and second pulse waveforms.

[0036] Also described herein is a method for treating diabetes, including advancing a pulsed electric field device into a patient's duodenum. The pulsed electric field device may include a first elongate body, a second elongate body positioned within the first elongate body, and an expandable member wrapped around the second elongate body. The expandable member may include an electrode array. The second elongate body may be rotated relative to the first elongate body to deploy the expandable member and bring duodenal tissue into contact with the electrode array. A pulse waveform may be delivered to the electrode array to generate a pulsed or modulated electric field, thereby treating duodenal tissue.

[0037] In some variations, a visualization device can be advanced through the lumen of the deployed expandable member. In some variations, rotating the first elongate body deploys one or more turns of the expandable member. In some variations, the expandable member includes a temperature sensor and further includes measuring tissue temperature using the temperature sensor. Delivery of the pulse waveform can be modulated based on the measured temperature.

[0038] In some variations, rotating the first elongate body can transition the expandable member to the expanded configuration. In some variations, the expandable member can include a lumen having a first diameter in the compressed configuration and a second diameter in the expanded configuration. The second diameter can be smaller than the first diameter. A third elongate body can be advanced through the lumen in the expanded configuration. In some variations, the expandable member can include a second expandable member disposed distal to the expandable member. The second expandable member can be expanded. In some variations, the pulse waveform includes a frequency of about 250 kHz to about 950 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A or about 0.6 A to about 65 A per square centimeter of tissue. For example, the current density can be from about 0.6 A to about 13 A per square centimeter of tissue from the electrode array. In some variations, fluid can be output between the pulsed electric field device and the duodenum from the expandable member.

[0039] In some variations, the pulsed or modulated electric field can be a therapeutic field at a first tissue depth of about 1 mm and a non-therapeutic field at a second tissue depth of at least about 1.5 mm. In some variations, tissue can be attracted to the expandable member during delivery of the pulse waveform.

[0040] Also described is a method for treating diabetes, comprising advancing a pulsed electric field device to a distal portion of a patient's duodenum. The pulsed electric field device may include an expandable member. The expandable member may include an electrode array and a temperature sensor. The expandable member may transition to an expanded configuration. A first pulse waveform may be delivered to the electrode array to generate a first pulsed electric field or a first modulated electric field, thereby treating the distal portion. A temperature sensor may be used to generate a visual marker on the distal portion. The pulsed electric field device may be retracted to a portion of the duodenum proximal to the distal portion based on the location of the visual marker. A second pulse waveform may be delivered to the electrode array to generate a second pulsed electric field or a second modulated electric field, thereby treating the second portion.

[0041] In some variations, a fluid can be output between the pulsed electric field device and the duodenum from the expandable member. In some variations, the visual marker can include one or more peaks. In some variations, the visual marker can be generated on the duodenum by raising the temperature of the mucosal tissue to about 49°C in less than about 2.5 seconds. In some variations, the visual marker can be configured to visually fade after about one day.

[0042] Also described is a device comprising an elongate body and an expandable member coupled to the elongate body. The expandable member can be configured to transition to an expanded configuration. An electrode array can be coupled to the expandable member. The electrode array can include a substrate, a first elongate electrode, and a second elongate electrode parallel to and spaced apart from the first elongate electrode. In some variations, the first elongate electrode and the second elongate electrode can have an interdigitated configuration. A first tissue temperature sensor can be disposed on the substrate between the first elongate electrode and the second elongate electrode.

[0043] In some variations, the first sensor may have a temperature resolution of less than about 0.5° C. In some variations, the first sensor may have a thermal diffusion time constant of less than about 5 milliseconds.

[0044] In some variations, the second temperature sensor can be configured to generate a visual marker on the tissue. In some of these variations, the second sensor can be disposed on the substrate along the periphery of the first and second elongated electrodes. The second sensor can have a helical or serpentine shape.

[0045] In some variations, the first sensor may include an insulator configured to maintain a pulse waveform configured to generate a pulsed or modulated electric field for treating tissue without breakdown. In some variations, the insulator may include a thickness of at least about 0.02 mm. In some variations, the first sensor may include a width of up to about 0.07 mm and a length of at least about 2 cm. In some variations, the distance between the first sensor and the first or second elongated electrode may be at least about 0.2 mm. In some variations, the first sensor may extend substantially parallel to the first elongated electrode and the second elongated electrode. In some variations, the expandable member may include a fluid opening. In some variations, the expandable member may include one or more fluid pathways.

[0046] Also described herein are methods for treating diabetes, including advancing a pulsed electric field device into a patient's duodenum. The pulsed electric field device may include an expandable member. The expandable member may include an electrode array and a temperature sensor. The expandable member may be transitionable to an expanded configuration. A pulse waveform may be delivered to the electrode array to generate a pulsed or modulated electric field, thereby treating the duodenum. The temperature of the duodenal tissue may be measured using the temperature sensor. In some variations, the reference generator is a temperature sensor. In some variations, the reference generator may be used to generate a visual marker on the duodenal tissue. In some variations, the visual marker may be visualized. The treatment region may be identified based on the visual marker. In some variations, a fluid may be output between the pulsed or modulated electric field device and the duodenum from the expandable member. In some variations, the pulsed or modulated electric field can be a therapeutic field at a first tissue depth of about 1 mm and a non-therapeutic field at a second tissue depth of at least about 1.5 mm. In some variations, tissue can be attracted to the expandable member during delivery of the pulse waveform.

[0047] Also described herein are systems comprising an elongate body and an expandable member coupled to the elongate body, the expandable member having a compressed configuration and an expanded configuration. The expandable member may further comprise an electrode array comprising a plurality of electrodes. A signal generator may be coupled to the electrode array. The signal generator may be configured to deliver a pulsed or modulated electric field waveform to the electrode array to generate a spatially varying electric field of up to about 20% at a predetermined treatment distance from the electrode array. In some variations, the electrode array may comprise a plurality of electrodes having a ratio of center-to-center distance between adjacent electrodes to width of about 2.3:1 to about 3.3:1. In some variations, the plurality of elongate electrodes has a center-to-center distance between adjacent electrodes of less than about 5 mm. In some variations, the surface area of ​​the plurality of electrodes comprises about 4% to about 100% of the circumference of the duodenum. In some variations, a fluid source may be in fluid communication with the electrode array. In some variations, one or more of the plurality of electrodes may include a fluid opening. In some variations, one or more of the plurality of electrodes may include a fluid pathway in fluid communication with the fluid opening. In some variations, the system may be configured to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm.

[0048] Also described is a device comprising an elongate body and an electrode array coupled to the elongate body. The electrode array may include a plurality of electrodes and a fluid opening. In some variations, one or more of the plurality of electrodes comprises a fluid path. In some variations, one or more of the plurality of electrodes includes a fluid opening. In some of these variations, the fluid opening is disposed on a vertex of one or more of the plurality of electrodes.

[0049] In some variations, the electrode array may include a substrate including a fluid opening. In some of these variations, the substrate may include one or more fluid paths. In some variations, a fluid source may be in fluid communication with the electrode array. In some variations, the expandable member may include a fluid opening. In some variations, the expandable member may include one or more fluid paths. In some variations, fluid may be output between the pulsed electric field device and the duodenum from the expandable member. In some variations, the plurality of elongated electrodes may include a center-to-center distance between adjacent electrodes of less than about 5 mm. In some variations, a visual marker may be visualized. A treatment area may be identified based on the visual marker.

[0050] In some variations, a signal generator can be coupled to the electrode array and configured to generate a pulse waveform having a frequency of about 500 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 2500 V, and a current density from the electrode array of about 0.6 A per square centimeter to about 100 A per square centimeter of tissue. In some variations, the ratio of the depth of the pulsed or modulated electric field to the depth of the treated duodenal tissue can be about 0.3 to about 0.5. In some variations, the ratio of expanded submucosal tissue to unexpanded duodenal mucosal tissue can be about 0.40 to about 0.60, and the ratio of expanded submucosal tissue to unexpanded duodenal submucosal tissue can be about 0.15 to about 0.35. In some variations, the expandable member can include one or more openings between adjacent electrodes. In some variations, the one or more openings can be configured for one or more of fluid ejection, fluid aspiration, and tissue aspiration. In some variations, the treated duodenum may be histologically indistinguishable from native tissue after about 30 days. In some variations, the pulsed or modulated electric field may be substantially uniform at a predetermined tissue treatment depth of about 0.5 mm to about 1.5 mm.

[0051] In some variations, the signal generator can be configured to inhibit delivery of the pulse waveform based on temperature. In some variations, the signal generator can be configured to resume delivery of the pulse waveform based on one or more of a predetermined period and temperature. In some variations, the temperature can be a temperature change of up to about 6°C. In some variations, the tissue temperature can be about 43°C. In some variations, the predetermined period can be up to about 60 seconds. In some variations, the electrode array can have a height of about 0.003 inches to about 0.015 inches, a distance between adjacent electrodes of about 1.0 mm to about 1.4 mm, and a pad width of about 0.5 mm to about 0.7 mm. In some variations, the electrode array can have a bipolar configuration. In some variations, the electrodes of the electrode array can be spaced apart by about 0.5 mm to about 2 mm. In some variations, the pulse waveform can have a voltage of about 450 V to about 700 V. In some variations, the device can be configured to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. In some variations, the expandable member can include a temperature sensor having a serpentine shape. In some variations, the expandable member can include a temperature sensor disposed generally perpendicular to the electrode array. In some variations, the reference generator can be configured to generate a visual marker on the tissue comprising one or more peaks. In some variations, the reference generator can be configured to generate a visual marker on the tissue comprising a polygon. In some variations, the reference generator can be configured to generate a visual marker on the tissue comprising a length of at least about 1 mm. In some variations, the reference generator can be configured to raise the temperature of the mucosal tissue to about 49° C. in less than about 2.5 seconds. In some variations, the reference generator can be configured to generate a visual marker on the tissue configured to visually fade after about 1 day. In some variations, the reference generator may be configured to generate a visual marker on the tissue with a depth of about 0.25 mm.In some variations, one or more of the openings in the expandable member can be configured to receive suction at a pressure of about 10 mmHg to about 200 mmHg. In some variations, one or more of the openings in the expandable member can be configured to draw tissue through one or more of the openings. In some variations, a set of twisted pair lead wires can be coupled to the electrode array. The present invention provides, for example, the following items. (Item 1) 1. An apparatus comprising: a first elongate body having a lumen; a second elongate body positioned at least partially within the lumen; and an expandable member wrapped around the second elongate body, the expandable member comprising an inner end coupled to the second elongate body, an outer end coupled to the first elongate body, and an electrode array. (Item 2) Item 10. The device of item 1, wherein the expandable member comprises a plurality of turns around the second elongate body. (Item 3) Item 10. The device of item 1, further comprising a connector coupling the first elongate body to the outer end of the expandable member. (Item 4) Item 10. The device of item 1, wherein the second elongate body is configured to rotate relative to the first elongate body to transition the expandable member between a rolled configuration and a deployed configuration. (Item 5) 5. The device of claim 4, wherein the expandable member comprises a lumen having a diameter of at least 10 mm in the deployed configuration. (Item 6) 6. A system comprising the device of item 5, further comprising a third elongate body disposed within the lumen of the expandable member. (Item 7) Item 7. The system of item 6, wherein the third elongate body comprises an endoscope. (Item 8) 2. The device of claim 1, further comprising a distal dilator and a proximal dilator coupled to one of the first elongate body and the second elongate body, wherein the expandable member is disposed between the distal dilator and the proximal dilator. (Item 9) Item 10. The device of item 1, further comprising one or more of a gear and a friction roller coupled to the second elongate body, wherein the expandable member comprises a track configured to couple to one or more of the gear and friction roller. (Item 10) Item 10. The device of item 9, wherein the track comprises a plurality of spaced openings in the expandable member. (Item 11) Item 10. A system comprising the device of item 1, further comprising a signal generator coupled to the electrode array, the signal generator configured to generate a pulse waveform having a frequency of about 250 kHz to about 950 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A per square centimeter of tissue. (Item 12) Item 10. The system of item 1, wherein the signal generator is configured to inhibit delivery of the pulse waveform based on the temperature of the tissue. (Item 13) 2. The device of claim 1, wherein the electrode array is configured to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. (Item 14) Item 10. The device of item 1, wherein the expandable member comprises a temperature sensor having a serpentine shape. (Item 15) Item 1, wherein the expandable member defines one or more openings therethrough. (Item 16) Item 10. The device of item 1, wherein the electrode array is configured to generate a therapeutic electric field that treats a predetermined set of cell types and does not treat muscle tissue. (Item 17) 2. The device of item 1, wherein the electrode array is configured to generate a therapeutic electric field that treats cells but leaves the tissue scaffold intact. (Item 18) 1. An apparatus comprising: A long, slender body and a plurality of elongated electrodes coupled to the elongated body, the plurality of elongated electrodes having a ratio of center-to-center distance between adjacent electrodes to width of the electrodes of about 2.3:1 to about 3.3:1. (Item 19) 20. A system comprising the device of claim 18, further comprising a signal generator coupled to the plurality of electrodes, the signal generator configured to generate a pulsed or modulated electric field waveform comprising a frequency of about 250 kHz to about 950 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A per square centimeter of tissue. (Item 20) Item 19. The device of item 18, further comprising an expandable member coupled to the elongate body and comprising the plurality of electrodes, the expandable member comprising a compressed configuration and an expanded configuration. (Item 21) 21. The device of claim 20, wherein in the expanded configuration, the expandable member comprises a lumen, and the device further comprises a second elongate body disposed within the lumen of the expandable member. (Item 22) Item 16. The system of item 15, wherein the second elongate body comprises an endoscope. (Item 23) 21. The device of claim 20, wherein the proximal and distal portions of the expandable member are transparent. (Item 24) Item 21. The device of item 20, further comprising a second expandable member coupled to the elongate body. (Item 25) Item 25. The device of item 24, wherein the second expandable member is inflatable. (Item 26) Item 19. The device of item 18, wherein the plurality of elongated electrodes includes a first electrode and a second electrode, the second electrode being parallel to or interdigitated with the first electrode. (Item 27) Item 19. The apparatus of item 18, wherein the center-to-center distance between adjacent electrodes and the widths of the plurality of elongated electrodes are substantially equal. (Item 28) 20. The device of claim 18, further comprising a tissue contact layer disposed on the elongate electrode, the tissue contact layer having a lower conductivity than the conductivity of the elongate electrode. (Item 29) Item 28. The device according to item 27, wherein the electrical conductivity of the tissue contact layer is from about 0.03 S / m to about 0.9 S / m. (Item 30) Item 19. The device of item 18, wherein the tissue contact layer has a thickness of about 10% to about 20% of the width of the electrode. (Item 31) Item 19. The device of item 18, wherein at least one of the electrodes has a semi-elliptical cross-sectional shape. (Item 32) Item 19. The device according to item 18, wherein the ratio of electrode height to electrode width is about 1:4 to about 1:8. (Item 33) Item 19. The device of item 18, wherein the adjacent electrodes are spaced apart by a weighted average distance of about 0.3 mm to about 6 mm. (Item 34) Item 19. The device of item 18, further comprising a hydrophilic layer disposed on the plurality of electrodes. (Item 35) Item 19. The device of item 18, wherein the surface area of ​​the plurality of electrodes comprises about 20% to about 45% of the surface area of ​​the expandable member in a given configuration. (Item 36) 1. A system comprising: A long, slender body and an expandable member coupled to the elongate body, the expandable member having a compressed configuration and an expanded configuration, the expandable member further comprising an electrode array comprising a plurality of electrodes; a signal generator coupled to the electrode array, the signal generator configured to deliver a pulsed or modulated electric field waveform to the electrode array to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. (Item 37) 1. A system comprising: A long, slender body and an expandable member coupled to the elongate body, the expandable member having a lumen, a compressed configuration, and an expanded configuration, the expandable member comprising an electrode array, the lumen of the expandable member configured to releasably receive a visualization device. (Item 38) Item 38. The system of item 37, wherein the lumen defines a central longitudinal axis of the expandable member. (Item 39) Item 38. The system of item 37, wherein the expandable member includes one or more openings extending therethrough. (Item 40) 40. The system of claim 39, wherein the visualization device is configured to aspirate tissue through the one or more openings at a pressure of about 10 mmHg to about 200 mmHg. (Item 41) 1. A system comprising: A long, slender body and an expandable member coupled to the elongate body, the expandable member having a lumen, a compressed configuration, and an expanded configuration, the expandable member comprising an electrode array; a visualization device configured to releasably couple to a lumen of the expandable member. (Item 42) Item 42. The system of item 41, wherein the visualization device comprises an aspiration lumen. (Item 43) Item 42. The system of item 41, wherein the visualization device comprises an aspiration lumen and an irrigation lumen. (Item 44) 1. A method of treating diabetes, comprising: advancing a pulsed electric field device into the patient's duodenum, the pulsed electric field device comprising an elongate body and an expandable member coupled to the elongate body, the expandable member comprising an electrode array; delivering a pulsed waveform to the electrode array to generate a pulsed or modulated electric field, thereby treating the duodenum. (Item 45) Item 45. The method of item 44, wherein the electrode array comprises a plurality of spaced electrodes forming parallel lines and / or an interdigitated configuration. (Item 46) 46. ​​The method of claim 45, further comprising configuring adjacent parallel lines of the electrode array with alternating polarity. (Item 47) 47. The method of claim 46, wherein the pulsed or modulated electric field varies spatially by up to about 20% at a given treatment distance from the electrode array. (Item 48) Item 45. The method of claim 44, wherein the expandable member includes a lumen therethrough, the method further comprising advancing an endoscope through the lumen of the expandable member. (Item 49) 49. The method of claim 48, further comprising retracting the endoscope to view the duodenal tissue proximal to the expandable member. (Item 50) Item 46. The method of item 45, wherein each of the plurality of electrodes is an elongated electrode. (Item 51) Item 46. The method of item 45, wherein each of the plurality of electrodes is a semi-elliptical electrode. (Item 52) 45. The method of claim 44, further comprising measuring the temperature at the expandable member during delivery of the pulsed waveform. (Item 53) 53. The method of claim 52, further comprising inhibiting delivery of the pulse waveform based on the measured temperature. (Item 54) 45. The method of claim 44, wherein the pulsed or modulated electric field is a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. (Item 55) Item 45. The method of item 44, further comprising aspirating tissue into the expandable member at a pressure of about 10 mmHg to about 200 mmHg. (Item 56) 1. A method of treating diabetes, comprising: advancing a pulsed electric field device toward a first portion of the patient's duodenum, the pulsed electric field device comprising an expandable member comprising an electrode array; transitioning the expandable member to an expanded configuration; delivering a first pulse waveform to the electrode array to generate a first pulsed electric field or a first modulated electric field, thereby treating the first portion; advancing the pulsed electric field device toward the second portion of the duodenum; delivering a second pulse waveform to the electrode array to generate a second pulsed electric field or a second modulated electric field, thereby treating the second portion. (Item 57) the expandable member comprises a temperature sensor, and the method further comprises: measuring the temperature of the tissue using the temperature sensor; 57. The method of claim 56, further comprising modulating pulse waveform delivery based on one or more of the measured temperature and rate of temperature change. (Item 58) Item 57. The method of item 56, further comprising unfolding the expandable member to transition the expandable member to the expanded configuration. (Item 59) Item 57. The method of item 56, wherein the expandable member includes a lumen having a first diameter in the compressed configuration and a second diameter in the expanded configuration, the second diameter being larger than the first diameter, and the method further comprises advancing a third elongate body through the lumen in the expanded configuration. (Item 60) Item 57. The method of item 56, wherein the expandable member comprises a second expandable member disposed distally of the expandable member, the method further comprising inflating the second expandable member. (Item 61) Item 57. The method of item 56, wherein deploying the expandable member includes deploying one or more turns of the expandable member. (Item 62) Item 57. The method of item 56, wherein the first and second pulse waveforms have a frequency of about 250 kHz to about 950 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A per square centimeter of tissue. (Item 63) 57. The method of claim 56, wherein one or more of the first pulsed electric field or the first modulated electric field and the second pulsed electric field or the second modulated electric field is a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. (Item 64) 57. The method of claim 56, further comprising aspirating tissue into the expandable member during one or more of the delivery of the first pulsed waveform and the second pulsed waveform. (Item 65) 1. A method of treating diabetes, comprising: advancing a pulsed electric field device into the patient's duodenum, the pulsed electric field device comprising a first elongate body, a second elongate body positioned within the first elongate body, and an expandable member wrapped around the second elongate body, the expandable member comprising an electrode array; rotating the second elongate body relative to the first elongate body to deploy the expandable member and bring duodenal tissue into contact with the electrode array; delivering a pulse waveform to the electrode array to generate a pulsed or modulated electric field, thereby treating the duodenal tissue. (Item 66) 66. The method of claim 65, further comprising advancing a visualization device through the lumen of the deployed expandable member. (Item 67) Item 66. The method of item 65, wherein rotating the first elongate body deploys one or more turns of the expandable member. (Item 68) the expandable member comprises a temperature sensor, and the method further comprises: measuring the temperature of the tissue using the temperature sensor; 66. The method of claim 65, further comprising modulating delivery of a pulse waveform based on the measured temperature. (Item 69) Item 66. The method of item 65, wherein rotating the first elongate body transitions the expandable member to the expanded configuration. (Item 70) Item 66. The method of item 65, wherein the expandable member includes a lumen having a first diameter in the compressed configuration and a second diameter in the expanded configuration, the second diameter being larger than the first diameter, and the method further includes advancing a third elongate body through the lumen in the expanded configuration. (Item 71) Item 66. The method of item 65, wherein the expandable member comprises a second expandable member disposed distally of the expandable member, the method further comprising inflating the second expandable member. (Item 72) Item 66. The method of item 65, wherein the pulse waveform comprises a frequency of about 250 kHz to about 950 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage of about 100 V to about 2 kV applied by the electrode array, and a current density from the electrode array of about 0.6 A to about 100 A per square centimeter of tissue. (Item 73) 66. The method of claim 65, wherein the pulsed or modulated electric field is a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. (Item 74) 66. The method of claim 65, further comprising aspirating tissue into the expandable member during delivery of the pulse waveform. (Item 75) 1. A method of treating diabetes, comprising: advancing a pulsed electric field device into a distal portion of the patient's duodenum, the pulsed electric field device comprising an expandable member, the expandable member comprising an electrode array and a temperature sensor; transitioning the expandable member to an expanded configuration; delivering a first pulse waveform to the electrode array to generate a first pulsed electric field or a first modulated electric field, thereby treating the distal portion; generating a visual marker on the distal portion using the temperature sensor; retracting the pulsed electric field device to a portion of the duodenum proximal to the distal portion based on the location of the visual marker; delivering a second pulse waveform to the electrode array to generate a second pulsed electric field or a second modulated electric field, thereby treating the second portion. (Item 76) Item 76. The method of item 75, wherein the visual marker comprises one or more peaks. (Item 77) 76. The method of claim 75, wherein the visual marker visually fades after about 1 day. (Item 78) 45. The method of claim 44, further comprising increasing the temperature of the mucosal tissue to about 49°C in less than about 2.5 seconds to generate a visual marker on the duodenum. (Item 79) Item 79. The method of item 78, wherein the visual marker is configured to visually fade after about 1 day. (Item 80) 1. An apparatus comprising: A long, slender body and an expandable member coupled to the elongate body and configured to transition to an expanded configuration; an electrode array coupled to the expandable member, the electrode array comprising a substrate, a first elongated electrode, and a second elongated electrode parallel to and spaced apart from the first elongated electrode; a first tissue temperature sensor disposed on the substrate between the first elongate electrode and the second elongate electrode. (Item 81) Item 81. The apparatus of item 80, wherein the first sensor has a temperature resolution of less than about 0.5°C. (Item 82) Item 81. The apparatus of item 80, wherein the first sensor has a thermal diffusion time constant of less than about 5 milliseconds. (Item 83) Item 81. The apparatus of item 80, further comprising a second temperature sensor configured to generate a visual marker on the tissue. (Item 84) Item 84. The device of item 83, wherein the second sensor is disposed on the substrate along a periphery of the first elongated electrode and the second elongated electrode. (Item 85) Item 84. The apparatus of item 83, wherein the second sensor comprises a spiral and / or serpentine shape. (Item 86) Item 81. The apparatus of item 80, wherein the first sensor comprises an insulator configured to maintain, without breakdown, a pulse waveform configured to generate a pulsed or modulated electric field for treating tissue. (Item 87) Item 87. The apparatus of item 86, wherein the insulator has a thickness of at least 0.02 mm. (Item 88) Item 81. The device of item 80, wherein the first sensor has a width of up to about 0.07 mm and a length of at least about 2 cm. (Item 89) Item 81. The device of item 80, wherein the distance between the first sensor and either the first elongated electrode or the second elongated electrode is at least 0.2 mm. (Item 90) Item 81. The apparatus of item 80, wherein the first sensor extends substantially parallel to the first elongated electrode and the second elongated electrode. (Item 91) 1. A method of treating diabetes, comprising: advancing a pulsed electric field device into the patient's duodenum, the pulsed electric field device comprising an expandable member, the expandable member comprising an electrode array and a temperature sensor; transitioning the expandable member to an expanded configuration; delivering a pulse waveform to the electrode array to generate a pulsed or modulated electric field, thereby treating the duodenum; measuring the temperature of the duodenal tissue using the temperature sensor; generating a visual marker on the duodenal tissue using a fiducial generator. (Item 92) Item 92. The method of item 91, wherein the reference generator is the temperature sensor. (Item 93) Item 92. The method of item 91, wherein the pulsed or modulated electric field is a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. (Item 94) 92. The method of claim 91, further comprising aspirating tissue into the expandable member during the delivery of the pulse waveform. (Item 95) 1. A system comprising: A long, slender body and an expandable member coupled to the elongate body, the expandable member having a compressed configuration and an expanded configuration, the expandable member further comprising an electrode array comprising a plurality of electrodes; a signal generator coupled to the electrode array, the signal generator configured to deliver a pulsed or modulated electric field waveform to the electrode array to produce an electric field that varies spatially by up to about 20% at a predetermined treatment distance from the electrode array. (Item 96) Item 96. The system of item 95, wherein the electrode array comprises a plurality of electrodes with a ratio of center-to-center distance between adjacent electrodes to width of the electrodes of about 2.3:1 to about 3.3:1. (Item 97) Item 96. The system of item 95, wherein the surface area of ​​the plurality of electrodes comprises about 4% to about 30% of the surface area of ​​the duodenum. (Item 98) Item 96. The system of item 95, further comprising a fluid source in fluid communication with the electrode array. (Item 99) Item 96. The system of item 95, wherein one or more of the plurality of electrodes includes a fluid opening. (Item 100) Item 100. The system of item 99, wherein one or more of the plurality of electrodes comprises a fluid path in fluid communication with the fluid opening. (Item 101) Item 96. The system of item 95, wherein the system is configured to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. (Item 102) 1. An apparatus comprising: A long, slender body and An apparatus comprising: an electrode array coupled to the elongate body, the electrode array including a plurality of electrodes and a fluid opening. (Item 103) Item 103. The device of item 102, wherein one or more of the plurality of electrodes comprises a fluid path. (Item 104) Item 103. The device of item 102, wherein one or more of the plurality of electrodes comprises the fluid opening. (Item 105) Item 105. The device of item 104, wherein the fluid opening is disposed on the apex of one or more of the plurality of electrodes. (Item 106) Item 103. The device of item 102, wherein the electrode array comprises a substrate containing the fluid opening. (Item 107) Item 107. The apparatus of item 106, wherein the substrate comprises one or more fluid paths. (Item 108) 103. A system comprising the apparatus of claim 102, further comprising a fluid source in fluid communication with the electrode array. (Item 109) 81. The device of any one of items 1, 30, 37, and 80, wherein the expandable member comprises a fluid opening. (Item 110) 81. The device of any one of items 1, 30, 37, and 80, wherein the expandable member comprises one or more fluid pathways. (Item 111) 20. A system comprising the device of item 18, further comprising a fluid source in fluid communication with the expandable member. (Item 112) Item 19. The device of item 18, wherein one or more of the plurality of elongated electrodes includes the fluid opening. (Item 113) Item 19. The device of item 18, wherein one or more of the plurality of elongated electrodes comprises one or more fluid pathways. (Item 114) 20. A system comprising the apparatus of claim 18, further comprising a fluid source in fluid communication with the plurality of elongated electrodes. (Item 115) 92. The method of any one of items 44, 56, 65, 75, and 91, further comprising outputting fluid between the pulsed electric field device and the duodenum from the expandable member. (Item 116) Item 96. The system of item 95, wherein the plurality of elongated electrodes comprises a center-to-center distance between adjacent electrodes of less than about 5 mm. (Item 117) Item 19. The device of item 18, wherein the center-to-center distance between adjacent electrodes of the plurality of elongated electrodes is less than about 5 mm. (Item 118) visualizing the visual marker; 92. The method of claim 91, further comprising identifying a treatment area based on the visual marker. (Item 119) Item 10. A system comprising the device of item 1, further comprising a signal generator coupled to the electrode array, the signal generator configured to generate a pulse waveform having a frequency of about 500 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 2500 V, and a current density from the electrode array of about 0.6 A to about 100 A per square centimeter of tissue. (Item 120) 66. The method of any one of items 44 and 65, wherein the ratio of the depth of the pulsed electric field or the modulated electric field to the depth of the duodenal tissue to be treated is about 0.3 to about 0.5. (Item 121) Item 66. The method according to Item 65, wherein the ratio of expanded submucosal tissue to non-expanded mucosal tissue of the duodenum is about 0.40 to about 0.60, and the ratio of expanded submucosal tissue to non-expanded submucosal tissue of the duodenum is about 0.15 to about 0.35. (Item 122) Item 96. The system of item 95, wherein the expandable member includes one or more openings between adjacent electrodes. (Item 123) Item 123. The system of item 122, wherein the one or more openings are configured for one or more of fluid ejection, fluid suction, and tissue suction. (Item 124) 92. The method of any one of paragraphs 44, 65, and 91, wherein the treated duodenum is histologically indistinguishable from native tissue after about 30 days. (Item 125) 66. The method of any one of items 44 and 65, wherein the pulsed electric field or the modulated electric field is substantially uniform at a predetermined tissue treatment depth of about 0.5 mm to about 1.5 mm. (Item 126) 126. The apparatus of any one of items 1-125, wherein the signal generator is configured to inhibit delivery of the pulse waveform based on temperature. (Item 127) 127. The device of any one of items 1-126, wherein the signal generator is configured to resume delivery of the pulse waveform based on one or more of a predetermined period and temperature. (Item 128) 128. The apparatus of any one of items 1 to 127, wherein the temperature is a maximum temperature change of about 6°C. (Item 129) 129. The device of any one of items 1-128, wherein the tissue temperature is about 43°C. (Item 130) 130. The apparatus of any one of items 1 to 129, wherein the predetermined period of time is up to about 60 seconds. (Item 131) 131. The device of any one of items 1-130, wherein the electrode array comprises a height of about 0.003 inches to about 0.015 inches, a distance between adjacent electrodes of about 1.0 mm to about 1.4 mm, and a pad width of about 0.5 mm to about 0.7 mm. (Item 132) 132. The device of any one of items 1 to 131, wherein the electrode array has a bipolar configuration. (Item 133) 133. The device of any one of items 1 to 132, wherein the electrodes of the electrode array are spaced apart by about 0.5 mm to about 2 mm. (Item 134) 134. The apparatus of any one of items 1 to 133, wherein the pulse waveform comprises a voltage of about 450V to about 700V. (Item 135) 135. The device of any one of items 1-134, wherein the device is configured to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm. (Item 136) 136. The device of any one of items 1 to 135, wherein the expandable member comprises a temperature sensor having a serpentine shape. (Item 137) 137. The device of any one of items 1 to 136, wherein the expandable member comprises a temperature sensor disposed generally perpendicular to the electrode array. (Item 138) Item 138. The apparatus of any one of items 1 to 137, wherein the reference generator is configured to generate a visual marker on the tissue comprising one or more peaks. (Item 139) Item 139. The apparatus of any one of items 1 to 138, wherein the reference generator is configured to generate a visual marker on the tissue that comprises a polygonal shape. (Item 140) Item 139. The apparatus of any one of items 1 to 139, wherein the reference generator is configured to generate a visual marker on tissue having a length of at least about 1 mm. (Item 141) 141. The apparatus of any one of items 1-140, wherein the reference generator is configured to raise the temperature of the mucosal tissue to about 49°C in less than about 2.5 seconds. (Item 142) 142. The apparatus of any one of items 1-141, wherein the reference generator is configured to generate a visual marker on the tissue configured to visually fade after about one day. (Item 143) Item 143. The apparatus of any one of items 1-142, wherein the reference generator is configured to generate a visual marker on tissue with a depth of about 0.25 mm. (Item 144) 144. The device of any one of items 1 to 143, wherein one or more of the openings in the expandable member are configured to receive suction at a pressure of about 10 mmHg to about 200 mmHg. (Item 145) Item 145. The device of any one of items 1-144, wherein one or more of the openings in the expandable member are configured to aspirate tissue through the one or more openings. (Item 146) Item 146. The device of any one of items 1 to 145, further comprising a set of twisted pair leads coupled to the electrode array. (Item 147) 1. An apparatus comprising: A long, slender body and an expandable member coupled to the elongate body, the expandable member comprising a lumen and a plurality of elongate recesses formed by coupling an outer surface of the expandable member to an inner surface of the expandable member; a plurality of electrodes coupled to the expandable member. (Item 148) Item 148. The device of item 147, wherein the expandable member is concentrically coupled to the elongate body. (Item 149) Item 148. The device of item 147, wherein the elongate body is coupled to a side wall of the expandable member. (Item 150) Item 148. The device of item 147, further comprising a second expandable member coupled to the elongate body and disposed distal to the expandable member. (Item 151) Item 148. The device of item 147, wherein at least the proximal and distal ends of the second expandable member are transparent. (Item 152) Item 148. A system comprising the device of item 147, further comprising a second elongate body disposed within the lumen of the expandable member. (Item 153) Item 148. The device of item 147, wherein the plurality of electrodes comprises a plurality of parallel and / or interdigitated elongated electrodes. [Brief explanation of the drawings]

[0052] The patent or application file contains at least one drawing executed in color. Copies of this patent and patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0053] [Figure 1A] 1 is a cross-sectional view of the digestive tract showing various anatomical structures. [Figure 1B] Cross-sectional view of the duodenum. [Figure 2A] 1 is a cross-sectional schematic view of a portion of the small intestine. [Figure 2B] 1 is a cross-sectional schematic view of a portion of the small intestine. [Figure 2C] 1 is a cross-sectional schematic view of a portion of the small intestine. [Figure 3A] This is a cross-sectional image of the duodenum. [Figure 3B] Detailed cross-sectional images of various duodenal tissues. [Figure 3C] Detailed cross-sectional images of various duodenal tissues. [Figure 3D] Detailed cross-sectional images of various duodenal tissues. [Figure 3E] Detailed cross-sectional images of various duodenal tissues. [Figure 3F] Detailed cross-sectional images of various duodenal tissues. [Figure 4] FIG. 1 is a block diagram of an exemplary variation of a pulsed electric field system. [Figure 5A] 1A-1C are perspective views of exemplary variations of pulsed electric field devices in a compressed configuration. [Figure 5B] 1A-1C are perspective views of exemplary variations of pulsed electric field devices in expanded configurations. [Figure 5C] FIG. 5B is a detailed perspective view of the pulsed electric field device shown in FIG. 5A. [Figure 5D] FIG. 5C is a detailed perspective view of the pulsed electric field device shown in FIG. 5B. [Figure 6A] 1A-1C are perspective views of exemplary variations of expandable members in a rolled configuration. [Figure 6B] 1A-1C are perspective views of exemplary variations of expandable members in deployed configurations. [Figure 7A] 1A-1C are cross-sectional perspective views of exemplary variations of expandable members in deployed configurations. [Figure 7B] FIG. 7B is a detailed cross-sectional perspective view of the expandable member shown in FIG. 7A. [Figure 8A] 1A-1C are perspective views of exemplary variations of pulsed electric field devices in a wound configuration. [Figure 8B] 8B is a perspective view of an exemplary variation of the visualization device and pulsed electric field device shown in FIG. 8A in a partially deployed configuration. [Figure 8C] FIG. 8C is a perspective view of the visualization device and pulsed electric field device shown in FIG. 8B in an expanded configuration. [Figure 9A] 1A-1C are perspective views of exemplary variations of pulsed electric field devices in a wound configuration. [Figure 9B] 9B is a perspective view of an exemplary variation of the visualization device and pulsed electric field device shown in FIG. 9A in a deployed configuration. [Figure 10A] 1A-1C are perspective views of exemplary variations of pulsed electric field devices in a wound configuration. [Figure 10B] FIG. 10B is a detailed perspective view of the pulsed electric field device shown in FIG. 10A. [Figure 10C] 1A-1C are perspective views of exemplary variations of pulsed electric field devices in deployed configurations. [Figure 10D] 1A-1C are perspective views of exemplary variations of pulsed electric field devices in deployed configurations. [Figure 10E] FIG. 10E is a detailed perspective view of the pulsed electric field device shown in FIG. 10D. [Figure 11] 1A-1C are perspective views of exemplary variations of visualization devices and pulsed electric field devices in partially deployed configurations. [Figure 12A] 1A-1C are perspective views of exemplary variations of pulsed electric field devices. [Figure 12B] FIG. 12B is a cross-sectional side view of the pulsed electric field device shown in FIG. 12A. [Figure 12C] FIG. 12B is a detailed cutaway perspective view of the pulsed electric field device shown in FIG. 12A. [Figure 13A] 1A-1C are perspective views of exemplary variations of expandable members. [Figure 13B] FIG. 13B is a plan view of the expandable member shown in FIG. 13A in a deployed configuration. [Figure 13C] 10A-10C are cross-sectional views of exemplary variations of expandable members in a wound configuration and gears. [Figure 14A] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 14B] FIG. 14B is a cutaway perspective view of the pulsed electric field device and visualization device shown in FIG. 14A. [Figure 15A] 1 is a cutaway perspective view of an exemplary variation of a pulsed electric field device and visualization device. [Figure 15B] 1 is a cutaway perspective view of an exemplary variation of a pulsed electric field device and visualization device. [Figure 16] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 17] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 18] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 19] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 20] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 21] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 22] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 23] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 24] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 25] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 26] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 27] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 28A] 1A-1C are perspective views of exemplary variations of the expandable members of the pulsed electric field device and visualization device. [Figure 28B] FIG. 28B is a perspective view of the pulsed electric field device and visualization device shown in FIG. 28A. [Figure 28C] FIG. 28B is a perspective view of the pulsed electric field device and visualization device shown in FIG. 28A. [Figure 28D] FIG. 28B is a perspective view of the pulsed electric field device and visualization device shown in FIG. 28A. [Figure 28E] FIG. 28B is a perspective view of the pulsed electric field device and visualization device shown in FIG. 28A. [Figure 29A] 1A-1C are perspective views of exemplary variations of pulsed electric field devices and visualization devices. [Figure 29B] FIG. 29B is a perspective view of the pulsed electric field device removed from the visualization device shown in FIG. 29A. [Figure 30A] 1A-1C are perspective views of exemplary variations of pulsed electric field devices. [Figure 30B] FIG. 30B is a perspective view of the pulsed electric field device shown in FIG. 30A within a tissue lumen. [Figure 31] 1A-1C are perspective views of exemplary variations of pulsed electric field devices. [Figure 32] 1A-1C are perspective views of exemplary variations of pulsed electric field devices. [Figure 33A] 1A-1C are side views of exemplary variations of pulsed electric field devices. [Figure 33B] FIG. 33B is a perspective view of the pulsed electric field device shown in FIG. 33A. [Figure 34A] 1A and 1B are perspective views of exemplary variations of electrode arrays. [Figure 34B] FIG. 34B is a cross-sectional side view of the electrode array shown in FIG. 34A. [Figure 34C] 1A-1C are perspective views of exemplary variations of electrode arrays in deployed configurations. [Figure 35] 10 is a plot of electric field strength for an exemplary deformation of an electrode array. [Figure 36] 1 is a plot of the electric field strength of a conventional electrode array. [Figure 37] 1A-1C are schematic cross-sectional views of exemplary variations of electrode arrays and embossing dies. [Figure 38] 10A-10C are schematic cross-sectional views of exemplary variations of electrode arrays with tissue contacting layers. [Figure 39] 10A-10C are schematic cross-sectional views of exemplary variations of electrode arrays with tissue contacting layers. [Figure 40] 1A-1C are schematic cross-sectional side views of exemplary variations of electrode arrays. [Figure 41A] 1 is an electric field strength plot of an exemplary electrode array configuration. [Figure 41B] 1 is an electric field strength plot of an exemplary electrode array configuration. [Figure 41C] 1 is an electric field strength plot of an exemplary electrode array configuration. [Figure 41D] 1 is an electric field strength plot of an exemplary electrode array configuration. [Figure 42]10 is a plot of electric field strength for an exemplary deformation of an electrode array. [Figure 43] 1A-1C are perspective views of exemplary variations of expandable members comprising electrode arrays. [Figure 44] 1A-1C are perspective views of exemplary variations of expandable members comprising electrode arrays. [Figure 45A] 1A-1C are schematic diagrams of exemplary variations of electrode arrays. [Figure 45B] 1A-1C are schematic diagrams of exemplary variations of electrode arrays. [Figure 45C] 1A-1C are schematic diagrams of exemplary variations of electrode arrays. [Figure 45D] 1A-1C are plan views of electric field strength plots of exemplary variations of electrode arrays. [Figure 45E] FIG. 45E is a cross-sectional view of the electric field intensity plot of the electrode array shown in FIG. 45D. [Figure 46A] 1A-1C are schematic perspective views of exemplary variations of the coordinate system of an electrode array. [Figure 46B] 46B is an electric field intensity plot corresponding to the electrode array shown in FIG. 46A. [Figure 47A] 1A-1C are schematic plan views of exemplary variations in polarity configurations of electrode arrays. [Figure 47B] 47B is an electric field intensity plot corresponding to the electrode array shown in FIG. 47A. [Figure 48] 1A-1C are schematic plan views of exemplary variations of electrode arrays. [Figure 49] 1A-1C are perspective views of exemplary variations of electrode arrays of pulsed electric field devices. [Figure 50] 1A-1C are perspective views of exemplary variations of electrode arrays of pulsed electric field devices. [Figure 51A] 10A-10C are schematic circuit diagrams of exemplary variations of the electrode array, temperature sensor array, and reference generator. [Figure 51B] 10A-10C are schematic circuit diagrams of exemplary variations of the electrode array, temperature sensor array, and reference generator. [Figure 51C] 1 is an image of a visual marker generated by a reference generator. [Figure 51D]10A-10C are schematic circuit diagrams of exemplary variations of the electrode array, temperature sensor array, and reference generator. [Figure 52A] 10A-10C are schematic circuit diagrams of exemplary variations of the electrode array, temperature sensor array, and reference generator. [Figure 52B] FIG. 52B is a detailed diagram of the electrode array, temperature sensor, and reference generator schematic circuit diagram shown in FIG. 52A. [Figure 53] FIG. 2 is a schematic circuit block diagram of an exemplary variation of a signal generator. [Figure 54] 1 is a flow chart illustrating an exemplary variation of a method for treating diabetes. [Figure 55A] FIG. 1 is a schematic diagram of an exemplary variation of a method for treating diabetes. [Figure 55B] FIG. 1 is a schematic diagram of an exemplary variation of a method for treating diabetes. [Figure 55C] FIG. 1 is a schematic diagram of an exemplary variation of a method for treating diabetes. [Figure 55D] FIG. 1 is a schematic diagram of an exemplary variation of a method for treating diabetes. [Figure 55E] FIG. 1 is a schematic diagram of an exemplary variation of a method for treating diabetes. [Figure 55F] FIG. 1 is a schematic diagram of an exemplary variation of a method for treating diabetes. [Figure 56A] 1 is a perspective view of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 56B] 1 is a perspective view of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 56C] 1 is a perspective view of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 56D] 1 is a perspective view of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 56E] 1 is a perspective view of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 56F]1 is a perspective view of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 56G] 1 is a perspective view of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 56H] 1 is a perspective view of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 57] 1 is an image of an exemplary deformation of thermal markings on tissue. [Figure 58A] 1 is an image of an exemplary variation of a patient treatment procedure using a pulsed electric field device and a visualization device. [Figure 58B] 1 is an image of an exemplary variation of a patient treatment procedure using a pulsed electric field device and a visualization device. [Figure 58C] 1 is an image of an exemplary variation of a patient treatment procedure using a pulsed electric field device and a visualization device. [Figure 58D] 1 is an image of an exemplary variation of a patient treatment procedure using a pulsed electric field device and a visualization device. [Figure 58E] 1 is an image of an exemplary variation of a patient treatment procedure using a pulsed electric field device and a visualization device. [Figure 59] 1 is an image of an exemplary variation of an electrode array. [Figure 60] 1 is an image of an exemplary variation of a pulsed electric field device. [Figure 61A] 1A-1C are perspective views of images of exemplary variations of pulsed electric field devices and visualization devices. [Figure 61B] FIG. 61B is a detailed image of the pulsed electric field device and visualization device shown in FIG. 61A. [Figure 62A] 1 is an image of an exemplary variation of a pulsed electric field device. [Figure 62B] 1 is an image of an exemplary variation of a pulsed electric field device comprising a balloon. [Figure 62C] FIG. 62B is a perspective view of the pulsed electric field device shown in FIG. 62A. [Figure 63A] 1 is an image of an exemplary variation of a pulsed electric field device in a wound configuration. [Figure 63B] 1 is an image of an exemplary variation of a pulsed electric field device in a deployed configuration. [Figure 63C] FIG. 63C is a perspective view of the pulsed electric field device shown in FIG. 63B. [Figure 64A] 1 is an image of an exemplary variation of a pulsed electric field device and visualization device. [Figure 64B] 1 is an image of an exemplary variation of a pulsed electric field device in a deployed configuration within a tissue lumen. [Figure 65] 1 is an image of an exemplary variation of a pulsed electric field device. [Figure 66] FIG. 10 is a schematic circuit diagram of an exemplary variation of an electrode array. [Figure 67] 1 is an image of an exemplary variation of an electrode array. [Figure 68] 1 is an image of an exemplary variation of an electrode array. [Figure 69A] 1A and 1B are plan views of exemplary variations of electrode arrays. [Figure 69B] FIG. 69B is a perspective view of the electrode array shown in FIG. 69A. [Figure 69C] FIG. 69B is a perspective view of the electrode array shown in FIG. 69A. [Figure 69D] FIG. 69B is a perspective cross-sectional view of the electrode array shown in FIG. 69A. [Figure 70] 10 is an exemplary variation of a voltage plot comparing the voltage output of a pulsed electric field treatment with the voltage output of a radiofrequency treatment over time. [Figure 71A] 1 is a cross-sectional image of a pulsed electric field device in a dilated configuration dilating the duodenum. [Figure 71B] 1 is a cross-sectional image of an undilated duodenum. [Figure 71C] 1 is a cross-sectional image of an undilated duodenum. [Figure 71D] FIG. 71C is a detailed cross-sectional image of the undilated duodenum. [Figure 71E] This is a cross-sectional image of a dilated duodenum. [Figure 71F] FIG. 71E is a detailed cross-sectional image of the dilated duodenum. [Figure 72A] This is a detailed cross-sectional image of duodenal tissue approximately one day after treatment. [Figure 72B] This is a detailed cross-sectional image of duodenal tissue approximately one day after treatment. [Figure 73] This is a detailed cross-sectional image of duodenal tissue approximately three days after treatment. [Figure 74A] Detailed cross-sectional images of duodenal tissue approximately 7 days after treatment. [Figure 74B] Detailed cross-sectional images of duodenal tissue approximately 7 days after treatment. [Figure 75] This is a detailed cross-sectional image of duodenal tissue approximately 14 days after treatment. [Figure 76] 1A-1C are perspective views of exemplary variations of electrode arrays in deployed configurations. [Figure 77] 1A-1C are perspective views of exemplary variations of pulsed electric field devices in expanded configurations. [Figure 78A] 1 is an image of an exemplary variation of a pulsed electric field device in a contracted or compressed configuration. [Figure 78B] FIG. 78C is a detailed image of the deployed or expanded electrode array of the pulsed electric field device shown in FIG. 78B. [Figure 79A] 1 is an image of an exemplary variation of a pulsed electric field device in a compressed configuration. [Figure 79B] 1 is an image of an exemplary variation of a pulsed electric field device in an extended configuration. [Figure 79C] FIG. 79C is a detailed image of the deployed electrode array of the pulsed electric field device shown in FIGS. 79A and 79B. [Figure 80A] 10 is a plot of electric field strength for an exemplary deformation of an electrode array. [Figure 80B] 10 is a plot of electric field strength for an exemplary deformation of an electrode array. [Figure 81A] FIG. 1 is a schematic diagram of an exemplary variation of a method for treating diabetes. [Figure 81B] FIG. 1 is a schematic diagram of an exemplary variation of a method for treating diabetes. [Figure 81C] FIG. 1 is a schematic diagram of an exemplary variation of a method for treating diabetes. [Figure 82A]1 is an image of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 82B] 1 is an image of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 82C] 1 is an image of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 82D] 1 is an image of an exemplary variation of a method for treating diabetes using a pulsed electric field device and a visualization device. [Figure 83A] 10 is a plot of tissue temperature, voltage, and current over time for an exemplary variation of a method of treating tissue. [Figure 83B] 10 is a plot of tissue temperature, voltage, and current over time for an exemplary variation of a method of treating tissue. [Figure 84] FIG. 1 is a cross-sectional perspective view of a set of twisted pair lead wires. [Figure 85] 1A-1C are perspective views of exemplary variations of electrode arrays of pulsed electric field devices. DETAILED DESCRIPTION OF THE INVENTION

[0054] Described herein are devices, systems, and methods for treating tissue to address chronic diseases. For example, the devices, systems, and methods may include those for treating diabetes by treating a patient's duodenal tissue. In some variations, treating the duodenum may include treating at least about 30% of the mucosal lining of the duodenum with minimal trauma, damage, or scarring to the submucosa, vasculature, and muscle. For example, the mucosal layer of the duodenum may be treated using a pulsed electric field (PEF) system.

[0055] It may be useful to briefly identify and describe relevant small intestinal anatomical structures. Figure 1A is a cross-sectional view of the gastrointestinal tract of a patient (100). A visualization device (150) (e.g., an endoscope) is shown advanced through the esophagus (110) into the stomach (120). The stomach (120) connects to the duodenum (130). Figure 1B is a detailed cross-sectional view of the duodenum (130), which surrounds the upper portion of the pancreas (140). The duodenum is a "C"-shaped, hollow, jointed tubular structure, typically about 20 cm to about 35 cm in length and about 20 mm to about 45 mm in diameter. Figures 2A-2C are cross-sectional schematic diagrams of the layers of the small intestine (200), including the mucosa (210), submucosa (220), muscularis mucosae (230), and serosa (240). Treatment of the duodenum may include resurfacing the mucosa (210) as described herein. Access to the duodenum may be achieved by advancing the systems and devices described herein through one or more of the esophagus, stomach, pylorus, lower esophageal junction, cranio-pharyngeal junction, and several sharp, small radius bends throughout the length of the digestive tract.

[0056] A brief discussion of electroporation and the role of ohmic heating may be more useful. Electroporation is the application of an electric field to living cells, causing ions of opposite charge to accumulate on opposite sides of the cell membrane. Generally, electroporation requires a potential difference across the cell membrane on the order of about 0.5 to about 1 volt, with an accumulation duration on the order of about 1 to about 2 milliseconds. Electroporation inevitably produces ohmic heating, but there is considerable confusion in the literature regarding this, including a significant number of references that erroneously claim the existence of non-thermal electroporation. For example, the ionic conductivity σ ic An external uniform electric field of magnitude E applied to the intracellular fluid of ic and the thermal power density E 2 σ ic The medium dissipates heat. p and density p, the resulting rate of temperature rise is given by equation (1).

number

[0057] For example, a 1 kV / cm electric field acting on tissue with a conductivity of approximately 0.3 S / m, a heat capacity of approximately 3.7 Joules / (gm°C), and a density of approximately 1 gm / cc will heat the tissue at a rate of approximately 800°C / sec. Note that because tissue is an ionic conductor, there is no electric field within the tissue when no current flows through it. The initial time after an external electric field is suddenly applied to a membrane to accumulate charge can be on the order of approximately 30 nanoseconds, suggesting that the average temperature rise during the initial membrane charging phase can be tens of microdegrees. When an external electric field is applied and ionic currents charge the membrane surface, disrupting the electric field in the lipid bilayer, heating may be confined to the membrane on a timescale of less than a microsecond, although leakage currents may still flow. For example, if the conductivity of the lipid layer is σ li Using a ρ = 0.002 S / m, a potential of 1 volt across an 8 nm layer can be locally heated at an instantaneous rate of about 8 °C / microsecond. This heating rate decreases with time from the application of the external electric field, as heat can further diffuse out of the film.

[0058] When ionic currents are confined to pores in the cell membrane, current crowding results in correspondingly high heating rates within the pores. Because the pore area can be 1% or less of the membrane area, the current density within the pores can be 100 times higher than in the bulk tissue. This increases the heating rate by a factor of 10,000, leading to local heating rates on the order of 10 °C / microsecond.

[0059] Local temperature increase is a mechanism that contributes to the transition from electroporation to irreversible electroporation. Thermal diffusion reduces the local temperature change. For example, if the thermal diffusivity of tissue, κ, is 0.13 mmHg, 2 / s, the thermal diffusion length in 10 μs is

number

[0060] Bulk tissue remains a good ionic conductor during the electroporation process and heats at a rate on the order of approximately 800°C / s while the external electric field is applied. When the external electric field is removed, cell membranes can discharge in the order of approximately 30 nanoseconds, necessitating the continued application of an external voltage and current to induce pore formation and growth. Because the maximum allowable temperature rise in bulk tissue can be on the order of approximately 13°C, the maximum duration for which the external electric field can be applied, even in a bipolar configuration, can be in the range on the order of approximately 10 milliseconds. Because this heat is generated to a treatment depth of approximately several millimeters within the tissue, the time required to cool the tissue by conduction can be approximately 70 seconds (e.g., 3 mm). 2 ) / (0.13mm 2 / sec). Blood convection may dominate the observed cooling time, which is on the order of about 10 seconds. Electroporation may increase the bulk tissue temperature through a phase transition of the lipid cell membrane, which is 41°C in some cells on the duodenum. The phase transition temperature may be the temperature required to induce a change in the physical state of lipids from an ordered gel phase to a liquid crystalline phase.

[0061] Electroporation parameters can be varied to produce different effects on the tissue. Figure 3A is a cross-sectional image of an untreated duodenum (300A), including the muscularis (310A) and villi (320A). Figure 3D is an image of exemplary changes to duodenal tissue in its original, untreated state, including the muscularis (310D), submucosa (330D), villous crypts (340D), and villi (320D). As described in more detail herein, Figure 3E shows duodenal tissue that has undergone a majority heat treatment, and Figure 3F shows duodenal tissue that has undergone a majority pulsed or modulated electric field treatment. Treatments described herein (e.g., Figure 3F), which primarily treat the mucosal layer with preserved tissue structure that appears similar to native tissue, reduce trauma to the tissue compared to the heat treatment shown in Figure 3E.

[0062] Application of a pulsed electric field to duodenal tissue results in non-thermal tissue changes. For example, Figure 3D is an image of normal, untreated (e.g., native tissue) porcine duodenal mucosa. Figure 3F is an image of the initial mucosal histological appearance with progressive epithelial loss and structural / architectonic preservation of the lamina propria. For example, Figure 3F shows histological progression with complete native epithelial loss and early crypt regeneration within a preserved lamina propria. The glandular layer across Figures 3A-3D and 3F demonstrates structural preservation of the lamina propria after treatment. For example, histopathology confirms that the PEF treatment described herein, applied at a depth of approximately 1 mm in duodenal tissue, treats the mucosal layer without pulsed electric field energy affecting the lamina propria at the treatment level.

[0063] In some variations, pulsed electric field (PEF) treatment can be combined with localized thermal treatment. For example, thermal treatment can be applied to superficial or near-surface tissue, while PEF treatment can be applied to deeper tissue. As described in more detail herein, the depth of tissue treatment received by one or more layers can be adjusted based on one or more of the electrode design, applied voltage, time or duration of energy delivery, frequency of applied energy, and tissue composition. An example of such control is thermal treatment applied to a tissue depth of approximately 0.1 mm and PEF treatment applied to a tissue depth of approximately 1 mm. The ratio and depth of thermal treatment relative to PEF treatment can be based on the desired clinical outcome (e.g., efficacy). In some variations, thermal treatment can be applied to a tissue depth of approximately 3 mm, while PEF treatment can be applied to a tissue depth of approximately 5 mm. Thus, in some variations, more thermal treatment than PEF treatment can be applied to the tissue. Depending on the depth and type of tissue, different healing cascades may be optimal. In some variations, up to about 1 mm of the villous mucosa can be heat treated to essentially replace the entire tissue structure, and the submucosa can be PEF treated to preserve the tissue structure and promote rapid healing of that layer. Furthermore, neither heat nor PEF treatment can affect the deeper muscle layers.

[0064] Figure 3B shows images of exemplary changes in duodenal tissues subjected to different treatments. Specifically, the tissue (360) was treated with pulsed or modulated electric field energy, and the first mucosal region (362) was additionally exposed to radiofrequency energy. The excised villi in the first mucosal region (362) disrupted cell membranes and disrupted cellular structure, such that these cells are no longer viable or functional. In contrast, the second mucosal region (360) has cells that have undergone cytolysis, in which the cell membranes remain intact but the cells are no longer viable or functional. That is, cytolysis corresponds to functional cell death with intact cellular structure, while ablation represents the loss of both cellular structure and function. The submucosa (370) and muscularis mucosae (380) remain healthy (e.g., viable and fully functional with cellular integrity). In Figure 3B, villi in a first mucosal region (362) are thermally ablated, while cell lysis in a second mucosal region (360) is caused by a pulsed or modulated electric field. A third mucosal region (363), adjacent to the thermal lesion in the first mucosal region (362), is completely untreated and contains viable tissue.

[0065] Figure 3C shows a histological slide of duodenum from tissue approximately 24 hours after treatment with heat and pulsed electric fields, demonstrating partial processing of the mucosa down to the crypt layer, with damaged cells. The fourth mucosal region (391) corresponds to heat / heat-fixed tissue of the villi, including villus-associated enteroendocrine cells. The fourth mucosal region (391) demonstrates structural and cytological preservation, with cellular details characterized by hyperchromatic nuclear and hypereosinophilic cytoplasmic staining. Overall, no interstitial hemorrhage or infiltrating post-treatment associated inflammatory cells were identified. Sloughing of the heat-fixed tissue, followed by villous structural healing with surface re-epithelialization and crypt cell regrowth, can be expected. The crypt tissue is partially affected by the combined effects of heat and pulsed electric fields. The tissue healing timeline is expected to be longer than that of pulsed electric field treatment without the heat effect. The submucosa (370) and muscularis mucosae (380) are histologically unaffected. Figure 3E shows an example image of porcine duodenal histology 24 hours after isolated thermal tissue treatment (i.e., without concomitant pulsed electric field exposure) that disrupts the lamina propria, where the tissue scaffold is burned and destroyed, sloughing off and being removed during healing. This shows histological characteristics of thermal tissue dose consistent with heat-induced coagulation necrosis without heat fixation. In this area, glandular epithelial and neuroendocrine cells (321) show a loss of cytological detail, consistent with cellular "ghost images." Interstitial hemorrhage and reactive inflammatory cells in the mucosal layer (341) are present at the edges of the area. The submucosa (331) and muscularis mucosae (311) also show injury-related changes. This area can be expected to heal similarly to ischemic-type coagulation necrosis, with resorption and remodeling accompanied by mucosal regeneration. The thermal lesion destroyed the lamina propria. The scaffold is burned and destroyed, sloughing off and being removed during healing. The tissue healing time frame in this area needs to be longer than that expected with pulsed electric field treatment.

[0066] Figure 3F shows exemplary changes in duodenal tissue treated with pulsed or modulated electric field energy to a controlled depth that does not include the muscularis layer: an untreated muscularis mucosae layer (310), submucosa (330), submucosa (332), treated villous crypts (342) with partial cell lysis and maintained tissue scaffolding, and treated villi (322) with villous shedding. The treated submucosa (332) also maintains tissue scaffolding. These treated tissues exhibit cells that have undergone cell death, with the cell membrane remaining intact but the cells no longer viable and functional. A healing cascade replaces these cells without the infiltration of numerous inflammatory cells, the surface re-epithelializes, and villous structural healing and crypt cell repopulation occur. The muscularis mucosae (310) remain healthy (e.g., viable and fully functional with cellular integrity) even without the therapeutic effects of pulsed electric field energy. That is, with pulsed or modulated electric field energy, cell death corresponds to functional cell death with intact cellular structure, whereas ablation implies loss of both cellular structure and function, as well as an active necroinflammatory response and healing cascade.

[0067] In some variations, the target depth of treatment includes the mucosal layer but excludes the muscularis propria. Human tissue data evaluated through histopathology support a target depth of approximately 1 mm for PEF tissue treatment, where the pulsed electric field does not penetrate the muscularis propria at the treatment level. As a result, the mucosa shows healing progression with the initiation of crypt and glandular epithelial regeneration on day 1 (e.g., Figures 72A and 72B), continued epithelial development with surface re-epithelialization on day 3 (e.g., Figure 73), early cobblestone-like blunted villus development on day 7 (e.g., Figures 74A and 74B), and continued villus elongation and narrowing on day 14 (Figure 75). Based on the methods described herein, the healing response can be essentially complete in approximately 30 days. Furthermore, the systems, devices, and methods described herein can provide uniform treatment coverage throughout the circumference and length of the duodenum.

[0068] Some methods for treating diabetes may involve treating the duodenal submucosa without treating the muscularis mucosa. Conventional solutions do not consistently treat the submucosa without adversely affecting the muscularis mucosa. Instead, conventional solutions may add complex palliative steps, such as saline injection lifts, to protect the muscularis mucosa. For reference, the mucosal layer is typically approximately 0.5 mm to 1 mm thick, the submucosa is typically approximately 0.5 mm to 1 mm thick, and the muscularis mucosa is typically approximately 0.5 mm thick. Inducing damage to the muscularis mucosa can lead to adverse clinical outcomes. Furthermore, the anatomical structure along the circumference of the duodenum is not uniform, complicating efforts to treat only the submucosa and not the muscularis mucosa.

[0069] The methods described herein can selectively alter tissue viability in the duodenum by applying a predetermined pulsed or modulated electric field without losing the integrity of the majority of the treated tissue, and optionally without other treatment of the tissue to mitigate the pulsed or modulated electric field on a portion of the tissue. In contrast, RF-based energy treatments primarily cause heat-induced cell lysis (e.g., cell death) or ablation, which indiscriminately damage tissue, can disrupt cellular structure, and can be difficult to regulate, adversely affecting treatment outcomes. In some variations, the methods described herein can include applying a pulsed or modulated electric field to thermally induce localized necrotic cell death (e.g., local ablation) and cell lysis (e.g., functional cell death) in duodenal tissue directly adjacent to the electrode array within a predetermined depth range of the duodenal tissue (e.g., up to about 1 mm, about 0.5 mm to 0.9 mm), while minimizing physiological effects on tissue greater than the selected depth.

[0070] Figure 3F is an image of exemplary changes in duodenal tissue treated with pulsed or modulated electric field energy to a controlled depth. In Figure 3F, portions of the muscularis (310) and submucosa (330) are untreated (i.e., the energy delivered to the tissue has no effect on the tissue), while different portions of the villous crypts (342), villi (322), and submucosa (332) are treated. Thus, treatment applied to the duodenal tissue shown in Figure 3F results in a more superficial (e.g., closer to the tissue surface) treated submucosa (332) and a deeper, untreated muscularis (310). The treated tissue contains cells that have undergone cell lysis; while the tissue scaffold remains intact, the cells are no longer viable and functional. A gentle healing cascade replaces these cells. The muscularis mucosae (310) adjacent to the treated submucosa (332) remains healthy (eg, viable and fully functional with cellular integrity).

[0071] Pulsed or modulated electric fields near the electrode array cause some thermal heating of tissue, which can lead to tissue ablation, destroying both cellular structure and function. However, the cell lysis in tissue caused by the pulsed or modulated electric fields applied herein is at least 50% pore-induced and less than 50% thermally induced, so that the majority of cell death is functional cell death with intact cellular structure. For example, the thermal heating caused by pulsed or modulated electric fields is generally localized within a relatively small radius from each electrode of the electrode array and does not affect deeper layers of tissue, such as the muscularis.

[0072] The systems, devices, and methods described herein deliver energy to provide optimized treatment characteristics for each tissue layer, improving treatment outcomes. Near the tissue surface (e.g., less than about 0.5 mm, about 0.1 mm to about 0.5 mm), thermal heating can cause localized necrotic cell death in the tissue, which may slough off after treatment. At tissue depths of about 0.5 mm to about 1.3 mm (e.g., the duodenal mucosa), thermal heating is limited (e.g., about a 13°C increase or less than a 6°C increase), while pulsed or modulated electric fields can cause cell lysis. For example, the electric field strength at about 1.0 mm can be about 2.5 kV / cm. At tissue depths greater than 1.0 mm, energy delivered to the tissue can cause reversible electroporation with even less thermal heating, leaving deeper tissues substantially untreated. Thus, while still delivering pulsed or modulated electric field energy for mucosal cell lysis, thermal heating can be limited to the superficial tissue layer (e.g., less than about 0.5 mm, about 0.1 mm to about 0.5 mm).

[0073] For example, Figure 3C shows an image of an exemplary duodenal tissue deformation that has undergone the method of treating duodenal tissue described herein, in which the villi (391) are treated by a combination of thermal heating (e.g., greater than 50%) and pore-induced cell death (e.g., less than 50%). A pulsed or modulated electric field applied to the villous crypts and submucosal tissue (370) treated the tissue to a large extent (e.g., greater than 50%) of pore-induced cell death, with a smaller contribution (e.g., less than 50%) from thermal heating. The muscularis (380) is substantially untreated by the pulsed or modulated electric field or other methods. For example, the submucosal tissue in Figure 3C has not received a saline injection. The depth of treatment can be controlled so that predetermined portions of the mucosal layer, such as the villous crypts, remain untreated as desired. The configurations and shapes of the electrode arrays described herein may enable the tissue treatment characteristics described herein.

[0074] In contrast, conventional solutions that apply other forms of thermal energy (e.g., steam, radiofrequency, laser, heated liquid) to the duodenum thermally ablate through multiple layers of tissue (e.g., inducing greater than 50% heat-induced necrotic cell death and less than 50% pore-induced cell death), thereby disrupting the mucosal cellular structure at similar depths and potentially causing harmful thermal damage to the mucosa. In an attempt to mitigate the risk of unintended thermal damage when applying thermal energy to deeper layers of the duodenum (e.g., the muscularis), saline can be injected into a portion of the duodenal tissue (e.g., the submucosa (330)). This additional step further complicates the procedure and is not always sufficient to prevent unwanted thermal tissue damage. The pulsed or modulated electric field-based methods described here eliminate this additional step and enhance protection against unwanted tissue damage by improving the energy delivery characteristics generated by pulsed electric field devices.

[0075] In some variations, pulsed electric field therapy can be applied while monitoring and / or minimizing tissue temperature rise. For example, a predetermined increase in tissue temperature (e.g., about 1°C, about 2°C, about 3°C) may be followed by a pause in energy delivery (e.g., a predetermined time interval) to cool the tissue. In this manner, the total energy delivered can raise the tissue temperature below a predetermined threshold (e.g., below a safety limit). In some variations, the predetermined threshold can be up to about 3°C, about 6°C, about 10°C, or about 13°C, including all ranges and subvalues ​​therebetween.

[0076] Furthermore, the difficulties encountered with conventional solutions in controlling unwanted thermal tissue damage would steer one of ordinary skill away from using the pulsed or modulated electric field energy levels and methods described herein. In some variations, the tissue power density produced by pulsed or modulated electric fields can be several orders of magnitude higher than the tissue power density produced by radiofrequency ablation. For example, the power density ratio of similar designs for radiofrequency ablation is about 25 V. rms The pulsed electric field device is driven by approximately 600V. rmsWhen driven by a PEF, the peak power can be approximately 576. Thus, it is unexpected that the pulsed or modulated electric field methods described herein not only treat tissue, but also do so without excessive thermal tissue damage that would require mitigation procedures. Furthermore, increased power density may require additional insulation and protection for the pulsed electric field device, as well as a signal generator capable of producing such peak power levels. Generally, the duty cycle of PEF treatment can be several orders of magnitude lower than radiofrequency ablation to keep bulk tissue temperature rise below approximately 10°C. For example, radiofrequency ablation energy can generally be delivered continuously for several seconds. In some variations, PEF treatment can collectively accumulate an on-time of approximately 15 milliseconds over approximately 10 seconds for a net duty cycle of approximately 0.0015.

[0077] Figure 70 is a plot (7000) comparing the voltage output of pulsed electric field treatment (7010) with the voltage output of radio frequency treatment (7020) over time. During RF treatment (7020), energy can be delivered continuously within the time scale of Figure 70, while during PEF treatment (7010), energy is intermittently pulsed at a voltage output that is orders of magnitude higher than the voltage output for RF treatment (7020).

[0078] Generally, the devices described herein may include an elongate body coupled to an electrode array disposable in the lumen of the duodenum. In some variations, the device may further include an expandable member configured to releasably engage a portion of the duodenum. The expandable member may include or be coupled to an electrode array configured to generate a pulsed or modulated electric field. The electrodes of the electrode array may have predetermined dimensions and spacing configured to generate a pulsed or modulated electric field with a predetermined uniformity to treat desired tissue while limiting damage to other tissue. In some variations, the expandable member may expand and compress as needed to engage the inner diameter of the duodenum. In some variations, a system including the devices described herein may further include a signal generator configured to generate a pulse waveform for delivery to the electrode array to thereby treat the engaged tissue.

[0079] Methods are also described herein. In some variations, a method for treating duodenal tissue, for example to treat diabetes, can include advancing a pulsed electric field device toward a first portion of a patient's duodenum. The pulsed electric field device can include an expandable member including an electrode array. The expandable member can transition from a compressed configuration to an expanded configuration to bring the expandable member (and electrode array) close to or into contact with the inner surface of the duodenum. The expandable member can have flexibility to apply force against and match the inner circumference of the duodenum, which itself can have a range of diameters. A first pulse waveform can be delivered to the electrode array to generate a first pulsed electric field or a first modulated electric field to treat tissue in the first portion. The pulsed electric field device can be moved (e.g., advanced or retracted) toward a second portion of the duodenum (which can be distal or proximal to the first portion), and a second pulse waveform is delivered to the electrode array to generate a second pulsed electric field or a second modulated electric field, thereby treating tissue in the second portion. For example, in some variations, the signal generator can generate a driving voltage of about 400 V to about 1500 V, which can correspond to an electric field strength of about 400 V / cm and about 7000 V / cm, in the treatment portion of the duodenum. The expandable member can be in a compressed configuration, a semi-expanded configuration, and an expanded configuration during movement of the pulsed electric field device. In some variations, the visualization device can be configured to visualize one or more of the pulsed electric field device and the tissue. In some variations, temperature sensor measurements can be used to monitor and / or control the delivery of the pulse waveform. In some variations, current and voltage measurements can be used to monitor and / or control the delivery of the pulse waveform.

[0080] I. System overview The systems described herein may include one or more of the components used to treat tissue, such as, for example, a pulsed electric field device and a visualization device. Figure 4 is a block diagram of a variation of a pulsed electric field system (400) that includes one or more of a pulsed electric field device (410), a signal generator (430), a multiplexer (470), a visualization device (450), and a display (460).

[0081] In some variations, the pulsed electric field device (410) may include one or more (e.g., first and second) elongate bodies (412) sized and shaped to be placed in one or more body cavities of a patient, such as, for example, the esophagus, stomach, or small intestine. In some variations, the pulsed electric field device (410) may further include one or more expandable members (414), one or more electrode arrays (416), one or more dilators (418), a handle (420), one or more sensors (422), a guidewire (424), and a delivery catheter (426). The distal end of the pulsed electric field device (410) may include the dilator (418), and the guidewire (424) may extend from the lumen of the dilator (418). The expandable member (414) may include the electrode array (416). For example, as described in more detail herein, in some variations, the electrode array (416) can be coupled to a surface (e.g., an outer surface) of the expandable member (416), while in other variations, the electrode array itself can form the expandable member and / or the electrode array can be integral with the expandable member. In some variations, the expandable member (414) and / or electrode array (416) can be disposed adjacent to one or more expanders, for example, between at least one pair of expanders (418). In some variations, the pulsed electric field system (400) can optionally include a delivery catheter (426) configured to advance over the pulsed electric field device (410). Additionally or alternatively, the pulsed electric field device (410) can include one or more sensors (422) configured to measure one or more predetermined properties, such as temperature, pressure, impedance, etc.

[0082] As described above, the pulsed electric field system (400) may include a visualization device (450). In some variations, the visualization device (450) may be configured to visualize one or more steps of a treatment procedure. The visualization device (450) may assist in one or more of: advancing the pulsed electric field device (410), positioning the pulsed electric field device and / or its components (e.g., the electrode array (416)), and verifying the treatment procedure. For example, the visualization device (450) may be configured to generate image signals that are transmitted to a display (460) or output device. In some variations, the visualization device (450) may be advanced separately from and concurrently with the pulsed electric field device (410) during the treatment procedure. For example, the expandable member (414) of the pulsed electric field device (410) may be configured to retain the visualization device (450), such that the pulsed electric field device (410) translates with the visualization device (450) as it moves through the body. The expandable member (414) can expand to release the visualization device (450), thereby allowing freedom of movement of the visualization device (450). In other variations, the visualization device (450) can be integrated with the pulsed electric field device (450). For example, the expander (418) can include the visualization device (450).

[0083] The visualization device (450) may be any device (intracorporeal or extracorporeal) that assists a user in visualizing a treatment procedure. In some variations, the visualization device (450) may comprise one or more of an endoscope (e.g., a chip-on-chip camera endoscope, a three-camera endoscope), an image sensor (e.g., a CMOS or CCD array with or without a color filter array and associated processing circuitry), a camera, an endoscope, an external light source, and an ultrasound catheter. In some variations, an external light source (e.g., a laser, LED, lamp, etc.) may generate light that may be carried by a fiber optic cable. Additionally or alternatively, the visualization device (450) may comprise one or more LEDs to provide illumination. For example, the visualization device (450) may comprise a bundle of flexible optical fibers (e.g., a fiberscope). The fiber optic cable or fiberscope bundle may be configured to receive and transmit light from the external light source. The endoscope may comprise an image sensor configured to receive reflected light from tissue and a pulsed electric field device. It should be understood that visualization device (450) may comprise any device that allows or facilitates visualization of any portion of the pulsed electric field device and / or internal structures of the body. For example, visualization device may comprise a capacitance sensor array for real-time x-ray imaging and / or fluoroscopy technology.

[0084] In some variations, the signal generator (430) can be configured to provide energy (e.g., energy waveform, pulse waveform) to the pulsed electric field device (410) to treat a predetermined portion of tissue, such as duodenal tissue. In some variations, the PEF systems described herein can include a signal generator comprising an energy source and a processor. The signal generator can be configured to deliver a bipolar waveform to the electrode array, thereby delivering energy to the tissue (e.g., duodenal tissue). The delivered energy can assist in resurfacing the duodenal mucosa while minimizing damage to surrounding tissue. In some variations, the signal generator can generate one or more bipolar waveforms. In some variations, the signal generator can be configured to control waveform generation and delivery in response to received sensor data. For example, energy delivery can be modulated (e.g., inhibited) unless a measured temperature falls within a predetermined range.

[0085] In some variations, to limit neural stimulation, the pulse waveform may comprise, on average, about zero net current (e.g., generally balanced positive and negative current) and may have a non-zero duration of less than about 2 μsec or less than about 5 μsec. In some variations, the pulse waveform may comprise a square wave. For example, the pulse waveform may comprise a square in the voltage drive and current drive, or a square in the voltage drive and a sawtooth in the current drive. In some variations, one or more pulses may comprise half-sine waves for both the current and voltage. In some variations, one or more pulses may comprise two exponential functions with different rise and fall times. In some variations, the one or more pulses may comprise a bipolar pulse at a first potential followed by a pulse pair at a second potential lower than the first potential.

[0086] In some variations, a multiplexer (470) can be coupled to the pulsed electric field device (410). For example, the multiplexer (470) can be coupled between the signal generator (430) and the pulsed electric field device (410), or the signal generator (430) can include the multiplexer (470). The multiplexer (470) can be configured to select a subset of electrodes of the electrode array (416) to receive a pulse waveform generated by the signal generator (430) according to a predetermined sequence. Additionally or alternatively, the multiplexer (470) can be coupled to multiple signal generators and configured to select between waveforms generated by one of the multiple signal generators (430) for a selected subset of electrodes.

[0087] Pulsed Electric Field Device Generally, the pulsed electric field devices described herein may include an elongate body and an expandable member including an electrode array. The pulsed electric field device may be configured to facilitate deployment in and treatment of the duodenum. In some variations, the pulsed electric field device may be configured to apply pulsed or modulated electric field energy to the inner circumference of the duodenum. The devices described herein may be used to treat only a specific, pre-specified portion of the duodenum and / or the entire length of the duodenum. In some variations, the electrode array of the pulsed electric field device may generate an electric field strength of about 400 V / cm to about 1500 V / cm, about 1500 V / cm to about 4500 V / cm, at a treatment depth of about 0.5 mm to about 1.5 mm from the inner surface of the duodenum, e.g., about 1 mm, including all values ​​and subranges therebetween. In some variations, the electric field may decay such that the electric field strength is less than about 400 V / cm at about 3 mm from the inner surface of the duodenum. In some variations, a predetermined bipolar current and voltage sequence can be applied to the electrode array of a pulsed electric field device to generate a pulsed or modulated electric field. The generated pulsed or modulated electric field can be substantially uniform to reliably induce cell lysis in a predetermined portion of duodenal tissue. For example, the generated pulsed or modulated electric field can vary spatially up to about 20%, between about 5% and about 20%, between about 10% and 20%, and between about 5% and about 15% at a predetermined depth in the tissue, including all ranges and subvalues ​​therebetween. Furthermore, the pulsed electric field device can be biocompatible and resistant to gastric acid and intestinal fluids.

[0088] Expandable Member Generally, the expandable members described herein can be configured to change configurations to assist in positioning the electrode array relative to the duodenum during a treatment procedure. For example, the expandable member can expand to contact tissue and hold the pulsed electric field device (e.g., elongate body, electrode array, sensor) in place relative to the tissue. The expandable member can also partially expand to hold a visualization device in place relative to the pulsed electric field device. The expandable member can have a compressed configuration and an expanded configuration. As discussed in more detail herein, in some cases, the compressed configuration can be a rolled configuration, and the expanded configuration can be an expanded configuration. Furthermore, in some variations, the expandable member can have a semi-expanded (or partially expanded) configuration between the compressed and expanded configurations. Placing the expandable member in the compressed configuration can compact the size of the pulsed electric field device, which may enable it to be more easily advanced through one or more body cavities. Once properly positioned, the expandable member can transition to an expanded configuration, which allows the electrode array of the expandable member to contact all or a portion of the inner circumference of the duodenum. In some variations, the semi-expanded configuration may allow the expandable member to retain another device (e.g., a visualization device) within the lumen of the expandable member. Additionally or alternatively, a lumen may refer to a tubular or non-tubular structure having one or more openings, apertures, holes, slots, combinations thereof, etc.

[0089] 5A is a perspective view of a variation of a pulsed electric field device (500). As shown therein, the pulsed electric field device (500) may comprise a first elongate body (510) having a lumen therethrough and a second elongate body (520) positioned at least partially within the lumen of the first elongate body (510). The pulsed electric field device (500) may further comprise an expandable member (530), which may be wrapped around (e.g., in mechanical contact with) the second elongate body (520) about its longitudinal axis. For example, as shown in FIGS. 5A-5D, the expandable member (530) may include multiple turns around the second elongate body (520), such that the expandable member (530) forms multiple (e.g., two, three, four, five, or more) layers wrapped or wrapped around the second elongate body (520). That is, the expandable member (530) may be in mechanical contact with the second elongate body (520). In some variations, the expandable member (530) (e.g., a circuit board, a flex circuit) may include an electrode array (not shown for clarity), which may include any of the electrode arrays described herein. For example, in some variations, the expandable member may be a flex circuit, while in other variations, the expandable member may include a base layer, and the flex circuit may be coupled to the base layer. The electrode array may be disposed on an outer surface of the expandable member (530). In some variations, a connector (540) can couple the first elongate body (510) to the expandable member (530). For example, the connector (540) can be configured to provide structural support to the expandable member (530) such that at least a portion of the expandable member (530) can be substantially fixed relative to the first elongate body (510).

[0090] FIG. 5A illustrates a pulsed electric field device (500) with an expandable member (530) in a compressed or coiled configuration configured for advancement through one or more body cavities. In the compressed or coiled configuration, the expandable member (530) may have a generally cylindrical shape with a first inner diameter (e.g., luminal diameter) and a first outer diameter. FIG. 5B illustrates a pulsed electric field device (500) with the expandable member (530) in an expanded or deployed configuration configured for engaging tissue, such as the inner surface of the duodenum (not shown for clarity). In the expanded or deployed configuration, the expandable member (530) may have a generally elliptical or cylindrical shape, with second inner and outer diameters having predetermined dimensions that are greater than the first inner and outer diameters, respectively. The expandable member in the expanded configuration may have a predetermined flexibility configured to conform to the shape of the tissue it engages.

[0091] In some variations, the first and second elongate bodies (510, 520) can be configured to rotate axially relative to one another to transition the expandable member (530) between a compressed configuration, an expanded configuration, and a semi-expanded configuration therebetween. For example, the second elongate body (520) (e.g., an internal torsion member, rotatable member) can be rotatably positioned within the lumen of the first elongate body (510), such that rotation of the second elongate body (520) relative to the first elongate body (510) transitions the expandable member (530) between a rolled configuration and a deployed configuration. In some of these variations, the inner diameter of the lumen (550) of the expandable member (530) can be at least about 8 mm, at least about 10 mm, or between about 8 mm and about 10 mm in the deployed configuration, inclusive of all values ​​and subranges therebetween. As described in more detail herein, a visualization device (not shown) can be disposed within the lumen (550) of the expandable member (530) to assist in visualization. It should be understood that the pulsed electric field device (500) can be advanced next to the visualization device and / or over a guidewire. In some variations, the visualization device can be used to guide advancement and visualize the treatment procedure such that a guidewire and / or other visualization modalities (e.g., fluoroscopy) are not required.

[0092] In some variations, the expandable member (530) can be configured to transition between a compressed configuration and an expanded configuration. For example, the expandable member (530) can transition to a partially expanded or semi-expanded configuration (between the compressed and expanded configurations) to allow a visualization device (e.g., an endoscope) to be disposed within the lumen of the expandable member (530). In some variations, the inner surface of the expandable member can engage and retain the visualization device in the semi-expanded configuration.

[0093] As shown in the detailed perspective views of FIGS. 5C and 5D, the expandable member (530) may have an inner end (532) (e.g., the innermost portion of the roll) and an outer end (534) (e.g., the outermost portion of the roll). FIG. 5C shows the expandable member (530) in a compressed configuration, and FIG. 5D shows the expandable member (530) in an expanded configuration. In some variations, the inner end (532) may be coupled to (e.g., attached to) the second elongate body (520), and the outer end (534) may be coupled to (e.g., attached to) the first elongate body (510). In this manner, by coupling the ends of the expandable member (530) to the first and second elongate bodies (510, 520), the size and shape of the expandable member (530) may be better controlled. For example, an edge of the inner end (532) substantially parallel to the longitudinal axis of the second elongate body (520) can be attached to the outer surface of the second elongate body (520), such that the inner end (532) rotates with the rotation of the second elongate body (520). The direction of rotation (e.g., clockwise, counterclockwise) of the second elongate body (520) can determine the configuration (e.g., expansion or compression) of the expandable member (530). For example, rotating the second elongate body (520) in a clockwise direction relative to the first elongate body (510) can expand or deploy the expandable member (530), while rotating the second elongate body (520) in a counterclockwise direction relative to the first elongate body (510) can compress or rotate the expandable member, or vice versa.

[0094] In some variations, the connector (540) can couple the first elongate body (510) to the outer end (534) of the expandable member (530), allowing the expandable member (530) to expand and compress while maintaining its position relative to the first elongate body (510). In some variations, the connector can act as a torsional control arm between the expandable member (530) and the first elongate body (510). In some variations, the connector (540) can have a curved shape, such as an "S" shape, or can be straight (linear). The configuration shown in Figures 5C and 5D facilitates advancement of the device (500) in the compressed configuration by minimizing the size of the connector (540) and reducing the diameter of the compressed device (500).

[0095] In some variations, the electrode array can be electrically coupled to the first elongate body (510) through the connector (540). For example, one or more leads can be coupled to the electrode array through a lumen of the first elongate body (510) and a lumen of the connector (540). Additionally or alternatively, one or more leads can be coupled to the electrode array through a lumen of the second elongate body (520). In some variations, the connector (540) can be constructed of a rigid or semi-rigid material or a combination thereof, such that the position of the outer end (534) relative to the first elongate body (510) remains substantially the same between the compressed and expanded configurations. Additionally or alternatively, the expandable members described herein can include a bimetallic strip configured to expand and compress through ohmic heating.

[0096] FIG. 6A is a perspective view of a variation of the expandable member (600) in a rolled configuration, and FIG. 6B is a perspective view of the expandable member (600) in a deployed configuration. In some variations, the expandable member (600) may comprise a substrate (610), such as a flex circuit. Additionally, the expandable member (600) may comprise or be coupled to an electrode array (not shown). In some variations, the expandable member (600) may be constructed of a self-expanding material biased to expand to a predetermined shape and / or diameter. For example, the expandable member (600) may comprise one or more of a flexible polymeric material (e.g., polyamide, PET), nitinol, stainless steel, copper, gold, other metals, adhesives, combinations thereof, and the like. In some variations, expansion and compression of the expandable member (600) may be caused by contraction and advancement, respectively, of a sheath (e.g., a delivery catheter) over the expandable member (600). The expandable member in a rolled configuration may include one or more turns. In some variations, the expandable member (600) in the rolled configuration may have a diameter of about 6 mm to about 15 mm, inclusive of all ranges and subvalues ​​therebetween. In some variations, the expandable member (600) in the expanded configuration may have a diameter of about 10 mm to about 50 mm, inclusive of all ranges and subvalues ​​therebetween.

[0097] FIG. 7A is a cross-sectional perspective view of a portion of the expandable member (700) in a deployed configuration. In some variations, the expandable member (700) may comprise a substrate (710), such as a flex circuit and a support (720). In these variations, the support (720) may provide structural reinforcement to enable the expandable member (700) to expand and adhere to the inner surface of the duodenum. That is, the support (720) may help apply an apposition force against tissue to enable engagement with the expandable member (700) during a procedure. In some variations, the support (720) may comprise a stiffness greater than that of the substrate (710) and / or comprise one or more components (e.g., a sensor, a reference generator). In some cases, the support (720) may extend circumferentially along the radial edge of the expandable member (700). In some variations, the support (720) may be configured to add stiffness to the substrate (710) coupled to the electrode array. In some variations, the support (720) can be disposed along a surface of the substrate (710) opposite the electrode array (730). In some variations, the support (720) can be composed of a rigid or semi-rigid material or combinations thereof configured to facilitate expansion and compression of the expandable member (700), and can include one or more of nitinol, stainless steel, carbon, polymers, etc.

[0098] 7B is a detailed cross-sectional perspective view of an expandable member 700 comprising a substrate 710, a support 720, and an electrode array 730. As shown in FIG. 7B, the electrode array 730 may comprise a plurality of substantially parallel elongated electrodes disposed on an outer surface of the substrate 710. Additionally or alternatively, the plurality of elongated electrodes may comprise an interdigitated configuration. For example, the plurality of elongated electrodes may comprise a curved shape (e.g., S-shaped, W-shaped).

[0099] The electrode array (730) can be configured to modify the bending stiffness of the expandable member (700) to facilitate consistent expansion and compression of the expandable member (700). In some variations, the electrode array (730) can include a plurality of electrodes with a ratio of center-to-center distance between adjacent electrodes to electrode width of about 2.3:1 to about 3.3:1 and about 2.8:1 to about 3.0:1. In some variations, the plurality of elongated electrodes has a center-to-center distance between adjacent electrodes of less than about 5 mm. In some cases, the electrode array can include a plurality of semi-elliptical electrodes. In some variations, the electrode array (730) can include a plurality of electrodes configured to protrude and / or be recessed relative to the surface of the substrate (710). In some variations, one or more electrodes of the electrode array (730) can vary in height relative to the substrate (710) by about -0.25 mm to about 0.765 mm.

[0100] 8A-33B show additional pulsed electric field device variations. FIG. 8A is a perspective view of a pulsed electric field device (800) variation in a wound configuration. The device (800) in the wound configuration can be configured for advancement through one or more body cavities. In some variations, the pulsed electric field device (800) can include a first elongate body (810) having a lumen therethrough and a second elongate body (820) positioned at least partially within the lumen of the first elongate body (810). The expandable member (830) can be wound around or around the second elongate body (820). For example, the expandable member (830) can include multiple turns around the second elongate body (820). The expandable member (830) can be coupled to distal portions of the first elongate body (810) and the second elongate body (820). In some variations, the expandable member (830) (e.g., a circuit board, a flex circuit) can include an electrode array (not shown for clarity), which can include any of the electrode arrays described herein. For example, the electrode array can be disposed on an outer surface of the expandable member (830). In some variations, a connector (840) can couple the first elongate body (810) to the expandable member (830).

[0101] In some variations, the system including the device (800) may further include a third elongate body (850) disposed within the lumen of the expandable member (830). In some of these variations, the third elongate body (850) comprises a visualization device (e.g., an endoscope). FIG. 8B is a perspective view of a variation of the visualization device (850) (e.g., an endoscope) and the pulsed electric field device (800). In FIG. 8B, the expandable member (830) may transition to a partially deployed configuration (e.g., semi-expanded) sufficient for the visualization device (850) to be disposed within the lumen of the expandable member (830). For example, the device (800) may be configured to hold the visualization device (850) in a predetermined position relative to the device (800). In this manner, the pulsed electric field device (800) and the visualization device (850) may be advanced together through one or more body cavities to facilitate navigation and delivery to the duodenum. Once delivered to the target tissue region, the visualization device (850) can be detached from the pulsed electric field device (800) such that the visualization device (850) can move independently of the pulsed electric field device (800). Additionally or alternatively, the device (800) can include a coupling mechanism configured to releasably couple the device (800) to the visualization device (850). For example, the coupling mechanism can include one or more of a snare, a snap attachment, a wire loop, a grabber, forceps, combinations thereof, and the like.

[0102] FIG. 8C is a perspective view of the visualization device (850) and pulsed electric field device (800) in a deployed (i.e., fully deployed) configuration. For example, the third elongate body (850) can be configured to translate relative to the first elongate body (810) in the deployed configuration. The pulsed electric field device (800) and expandable member (830) in FIG. 8C show a deployed configuration configured to engage tissue, such as the inner surface of the duodenum (not shown for clarity). In some variations, the second elongate body (820) (e.g., an internal torsion member, a rotatable member) can be configured to rotate relative to the first elongate body (810) to transition the expandable member (830) between a rolled configuration and a deployed configuration. In some of these variations, the expandable member (830) can include a lumen (860) having a diameter of at least 10 mm in the deployed configuration.

[0103] Similar to the pulsed electric field device (500) of Figures 5A-5D, the expandable member (830) can have an inner end (e.g., an innermost portion of the roll) and an opposing outer end (e.g., an outermost portion of the roll), where the inner end can be coupled to the second elongate body (820) and the outer end can be coupled to the first elongate body (810). As described in more detail above with respect to Figures 5A-5D, the direction of rotation (e.g., clockwise, counterclockwise) of the second elongate body (820) can determine the expansion or compression of the expandable member (830).

[0104] In some variations, a connector (840) can couple the first elongate body (810) to the outer end of the expandable member (830). In some variations, an electrode array can be electrically coupled to the first elongate body (810) through the connector (840). For example, one or more leads can be coupled to the electrode array through the first elongate body (810) and the connector (840). Additionally or alternatively, one or more leads can be coupled to the electrode array through the second elongate body (820). In some variations, the connector (840) can be constructed of a rigid or semi-rigid material or a combination thereof, such that the position of the outer end relative to the first elongate body (810) remains substantially the same between the rolled configuration and the deployed configuration.

[0105] FIG. 9A is a perspective view of a variation of a pulsed electric field device (900) comprising multiple expandable members in a wound configuration. The device (900) in the wound configuration can be configured for advancement through one or more body cavities. In some variations, the pulsed electric field device (900) can comprise multiple outer elongate bodies (910), each comprising a lumen and a second elongate body (920) positioned at least partially within each lumen of the outer elongate body (910). Multiple expandable members (930) can be disposed along the length of the device (900) and can be rolled around the second elongate body (920). For example, each expandable member (930) can include multiple turns around the second elongate body (920). The multiple expandable members (930) can be coupled to a distal portion of the second elongate body (920). In some variations, each of the expandable members (930) (e.g., circuit board, flex circuit) may include an electrode array (not shown for clarity), which may include any of the electrode arrays described herein. The expandable members (930) may include the same electrode array or different electrode arrays. The electrode arrays may be disposed on the exterior surface of each of the expandable members (930). In some variations, each expandable member (930) may be coupled to its respective outer elongate body (910) by a respective connector (940). Thus, in some variations, the pulsed electric field device (900) may include two, three, or more connectors (940), one or more for each expandable member (930). A pulsed electric field device (900) including multiple expandable members (930) may allow for a longer length of tissue to be treated at one time, thereby reducing the need to reposition the device (900) multiple times for different portions of tissue. The length of each expandable member 930 and the spacing between each expandable member 930 can be the same or different. Energy can be delivered to multiple electrode arrays of the device 900 in any predetermined order. For example, the electrode arrays can generate pulsed or modulated electric fields simultaneously or in series with the same or different pulsed waveforms.That is, the electrode arrays can be operated independently.

[0106] In some variations, a system including the pulsed electric field device (900) may further include a third elongate body (950) disposed within the lumen of the expandable member (930). In some of these variations, the third elongate body (950) may include a visualization device (e.g., an endoscope). Figure 9B is a perspective view of a variation of the visualization device (950) (e.g., an endoscope) and the pulsed electric field device (900). For example, the third elongate body (950) can be configured to translate relative to the first elongate body (910) in the deployed configuration. The pulsed electric field device (900) and expandable member (30) in Figure 9B are shown in a deployed configuration configured to engage tissue, such as the inner surface of the duodenum (not shown for clarity). In some variations, the inner elongate body (920) (e.g., an inner torsion member, rotatable member) can be configured to rotate relative to the outer elongate body (910) to transition the plurality of expandable members (930) between a rolled configuration and a deployed configuration. In some of these variations, the plurality of expandable members (930) can each include a lumen (960) having a diameter of at least 10 mm in the deployed configuration. In some variations, a visualization device (950) can be disposed within the lumen (960) of each of the plurality of expandable members (930).

[0107] 5A-5D, each of the expandable members 930 may have an inner end (e.g., an innermost portion of a roll) and an outer end (e.g., an outermost portion of a roll), the inner end being coupled to the inner elongate body 920 and the outer end being coupled to at least one of the outer elongate bodies 910 and the electrode array. As described in more detail above with respect to FIGS. 5A-5D, the direction of rotation (e.g., clockwise, counterclockwise) of the inner elongate body 920 may determine the expansion or compression of each of the plurality of expandable members 930.

[0108] In some variations, a connector (940) can couple the outer elongate body (910) to the outer end of each expandable member (930). In some variations, the electrode array of each expandable member can be electrically coupled to the outer elongate body (910) through a connector (940). For example, one or more leads can be coupled to each electrode array through the outer elongate body (910) and the connector (940). Additionally or alternatively, one or more leads can be coupled to the electrode array through the inner elongate body (920). In some variations, each connector (940) can be constructed of a rigid or semi-rigid material or a combination thereof, such that the position of the outer end relative to the outer elongate body (910) remains substantially the same between the rolled and deployed configurations. In some variations, each electrode can include an independent lead.

[0109] In some variations, the pulsed electric field device may include one or more dilators configured to assist in advancing the device through one or more body cavities. Figure 10A is a perspective view of a variation of a pulsed electric field device (1000) in a wound configuration. As shown therein, the pulsed electric field device (1000) may include a first elongate body (1010) having a lumen therethrough and a second elongate body (1020) positioned at least partially within the lumen of the first elongate body (1010). The expandable member (1030) may be wound around the second elongate body (1020), as described in more detail herein. For example, the expandable member (1030) may include multiple turns around the second elongate body (1020). The expandable member (1030) can be coupled to the distal portions of the first elongate body (1010) and the second elongate body (1020).

[0110] In some variations, the expandable member (1030) (e.g., circuit board, flex circuit) may include an electrode array (not shown for clarity), which may include any of the electrode arrays described herein. For example, the electrode array may be disposed on an outer surface of the expandable member (1030). In some variations, the pulsed electric field device (1000) may further include one or more dilators. For example, the pulsed electric field device (1000) may include a distal dilator (1060) and a proximal dilator (1062), each of which is coupled to one of the first elongate body (1010) and the second elongate body (1020). The dilators (1060, 1062) can aid in smoothly advancing and / or retracting the pulsed electric field device (1000) through one or more body cavities and can help prevent the expandable member from getting caught on tissue. For example, the dilators (1060, 1062) can be configured to protect the edges of the expandable member (1030) from contacting tissue as the expandable member (1030) advances through a body cavity. One or more of the dilators may include a recess (1064). In some variations, the recess (1064) may have a shape configured to facilitate mating or coupling with another elongated member, such as a visualization device (e.g., an endoscope). The expandable member (1030) can be disposed between the distal dilator (1060) and the proximal dilator (1062). The lengths and tapers of the dilators of the device may be the same or different. For example, the distal dilator (1060) may have a steeper taper than the proximal dilator (1062). In some variations, the pulsed electric field device (1000) may include only a single distal dilator (1060).

[0111] 10B is a detailed perspective view of a pulsed electric field device (1000) with an expandable member (1030) in a coiled configuration. In some variations, the pulsed electric field device (1000) may further include a connector (1040) that can couple one or more of the first elongate body (1010), the distal dilator (1060), and the proximal dilator (1062) to the expandable member (1030). For example, the connector (1040) can couple the first elongate body (1010) to an outer end of the expandable member (1030). In some variations, an electrode array can be electrically coupled to the first elongate body (1010) through the connector (1040). For example, one or more leads can be coupled to the electrode array through the first elongate body (1010) and the connector (1040). Additionally or alternatively, one or more leads can be coupled to the electrode array through the second elongate body (1020). In some variations, the connector (1040) can be constructed of a rigid or semi-rigid material or a combination thereof, such that the position of its outer end relative to the first elongate body (1010) remains substantially the same between the rolled and deployed configurations. In some variations, the distal dilator (1060) and the proximal dilator (1062) are attached to the first elongate body (1010). In some variations, the maximum diameter of the dilators (1060, 1062) can be approximately the same as the diameter of the expandable member in the rolled configuration. For example, the dilators (1060, 1062) can have a maximum diameter of about 10 mm to about 15 mm, inclusive of all ranges and subvalues ​​therebetween, in which case the expandable member (1030) in the rolled configuration can have a diameter of about 8 mm to about 15 mm, inclusive of all ranges and subvalues ​​therebetween.

[0112] 10C, 10D, and 10E are perspective views of a pulsed electric field device (1000) with an expandable member (1030) in a deployed configuration. In the deployed configuration, the expandable member (1030) can be configured to engage tissue, such as the inner surface of the duodenum (not shown for clarity). In some variations, the second elongate body (1020) (e.g., an internal torsion member, a rotatable member) can be configured to rotate relative to the first elongate body (1010) to transition the expandable member (1030) between the rolled configuration and the deployed configuration. For example, the second elongate body (1020) can be rotatably positioned within the lumen of the first elongate body (1010). In some of these variations, the expandable member (1030) can include a lumen (1080), the diameter of which can increase between the rolled configuration and the deployed configuration. In some variations, the diameter of the expandable member lumen can be at least 8 mm in the deployed configuration. In some variations, the expandable member (1030) in the deployed configuration can have a diameter of about 10 mm to about 50 mm, and about 15 mm to about 50 mm, including all ranges and subvalues ​​therebetween.

[0113] In some variations, the system including the device may further include a third elongate body disposed within the lumen of the expandable member. In some of these variations, the third elongate body includes a visualization device (e.g., an endoscope). FIG. 11 is a perspective view of a visualization device (1150) (e.g., an endoscope) and a variation of the pulsed electric field device (1100). The pulsed electric field device (1100) may include a first elongate body (1110) having a lumen therethrough and a second elongate body (1120) positioned at least partially within the lumen of the first elongate body (1110). The expandable member (1130) may be wrapped around the second elongate body (1120). In some variations, the pulsed electric field device (1100) may further include one or more dilators. For example, the pulsed electric field device (1100) may include a distal dilator (1160) and a proximal dilator (1162), each of which is coupled to one of the first elongate body (1110) and the second elongate body (1120). In FIG. 11 , the expandable member (1130) may transition to a partially deployed configuration sufficient for the visualization device (1150) to be disposed within the lumen of the expandable member (1130). For example, the device (1100) may be configured to hold the visualization device (1150) in a predetermined position relative to the device (1100). In this manner, the pulsed electric field device (1100) and the visualization device (1150) may be advanced together through one or more body cavities.

[0114] In some variations, the rolled expandable member of a pulsed electric field device can transition configurations using an actuator, which allows for improved control over the expansion and / or compression of the expandable member. For example, the actuator may comprise a set of gears and / or friction rollers (e.g., knurled friction rollers) and a track configured for consistent transmission of rotational torque from the rotating elongate body to the expandable member. Figure 12A is a perspective view, and Figure 12B is a cross-sectional side view, of a variation of a pulsed electric field device (1200) comprising an actuator (1270). As shown therein, the pulsed electric field device (1200) may comprise a first elongate body (1210) comprising a lumen therethrough, a second elongate body (1212) positioned at least partially within the lumen of the first elongate body (1210), and the actuator (1270). The pulsed electric field device (1200) may further include an expandable member (1230) wrapped around the second elongate body (1212) and operably coupled to an actuator (1270), as described in more detail herein. In some variations, the pulsed electric field device (1200) may further include one or more dilators, such as a distal dilator (1250) and a proximal dilator (1252) coupled to one of the first elongate body (1210) and the second elongate body (1212). In some variations, one or more of the dilators (1250, 1252) may have a sigmoid shape. The actuator (1270) may be disposed between the distal dilator (1250) and the proximal dilator (1252). The expandable member (1230) can be disposed between a distal dilator (1250) and a proximal dilator (1252). The dilators (1250, 1252) can enable smooth translation of the pulsed electric field device (1200) through one or more body cavities, as described in more detail herein.

[0115] As described above, the pulsed electric field device (1200) may include an actuator operably coupled to the expandable member (1230) and configured to assist in the expansion (e.g., deployment) and compression (e.g., rolling) of the expandable member (1230). In some variations, the actuator may include one or more gears, which may interface with one or more tracks formed in the expandable member (1230). For example, in the variation shown in FIGS. 12A-12C, the actuator (1270) may include a first gear (1220) and a second gear (1222), each of which may be coupled to the second elongate body (1212). The expandable member (1230) may further include a first track (1232) on a first side thereof and a second track (1234) on a second side thereof. The first track (1232) can be operably coupled to the first gear (1220), and the second track (1234) can be operably coupled to the second gear (1222). In some of these variations, the first and / or second tracks (1232, 1234) can include a plurality of spaced-apart openings in the expandable member (1230) configured to receive the teeth of the respective gears (1220, 1222). The expandable member (1230) can be coupled to the second elongate body (1212) via the gears (1220, 1222). Figure 12C is a detailed cutaway perspective view of the pulsed electric field device (1200) showing the engagement of the teeth of the gears (1220, 1222) with the respective tracks (1232, 1234) of the expandable member (1230). Additionally or alternatively, the actuator may comprise a metal roller with a multi-tooth texture configured to press directly against the expandable member (1230). The metal roller may be configured to operate with a drum plotter or film canister-type mechanism. Similar to the pulsed electric field device (500) of FIGS. 5A-5D, the expandable member (1230) may have an inner end (e.g., the innermost portion of the roll) and an outer end (e.g., the outermost portion of the roll), the inner end being coupled to the second elongate body (1212) and the outer end being coupled to the first elongate body (1210).The direction of rotation (e.g., clockwise, counterclockwise) of the second elongate body (1212) can determine the expansion or compression of the expandable member (1230). In some variations, a connector (1240) can couple the second elongate body (1212) to the inner end of the expandable member (1230). The outer end of the expandable member (1230) can be coupled to one or more of the dilators (1220, 1222) and the first elongate body (1210). However, FIG. 12A shows the unattached outer end of the expandable member (1230) for illustrative purposes. In some variations, the expandable member (1230) in the rolled configuration can have a diameter of about 6 mm to about 15 mm, including all ranges and subvalues ​​therebetween. The expandable member (1230) in the rolled configuration can include one or more turns. In some variations, the expandable member (1230) in the expanded configuration can have a diameter of about 10 mm to about 50 mm, including all ranges and subvalues ​​therebetween.

[0116] In some variations, the electrode array can be electrically coupled to the second elongate body (1212) through a connector (1240). For example, one or more leads can be coupled to the electrode array via the second elongate body (1212) and the connector (1240). Additionally or alternatively, one or more leads can be coupled to the electrode array through the first elongate body (1210).

[0117] 13A is a perspective view of a variation of the expandable member (1330) of the pulsed electric field device (1300), showing the expandable member (1330) in a compressed configuration and showing the expandable member (1330) with corresponding alignment of the openings in the tracks (1332, 1334). The openings in the tracks (1332, 1334) can be sized and positioned to substantially overlap one another when the expandable member (1330) is in the compressed configuration, such that the teeth of the gears (e.g., gears (1220, 1222) can pass through and be positioned within multiple openings in the tracks (1332, 1334), as described in more detail herein. In some variations, the size and spacing of the tracks (1332, 1334) can be varied along the length of the expandable member (1330) to aid in smooth rolling and deployment.

[0118] 13B is a plan view of the expandable member (1330) and tracks (1332, 1334) in a deployed configuration. In some variations, the distance between adjacent openings (e.g., tracks) (1362, 1366) can vary along the length of the expandable member (1330). In particular, the distance between adjacent openings (1362, 1366) can increase along the longitudinal axis of the expandable member (1330) from the first end (1302) of the expandable member to the second end (1304) of the expandable member. For example, dimension D (1366) of a first portion of the expandable member (1330) adjacent to or near the first end (1302) or at the first end (first end) can be smaller than dimension B (1362) of a second portion of the expandable member (1330) adjacent to or near the second end (1304) or at the second end (second end). Conversely, the length of each opening (1360, 1364) can decrease along the longitudinal axis of the expandable member (1330) from the first end (1302) to the second end (1304). For example, the length of dimension C (1364) adjacent to or near the first end (1302) or at the first end can be longer than the length of dimension A (1360) adjacent to or near the second end (1304). This spacing and opening shape can allow the expandable member to form a more precise and compact shape around the gear in a wound configuration, as shown in FIG. 13C, which is described in more detail below.

[0119] An expandable member (1330) with variable length openings and distances between openings may allow for a more compact winding configuration around a gear having a gear body (1342) and curved or angled teeth extending therefrom, as shown in FIG. 13C. FIG. 13C is an exemplary variation of an expandable member (1330) (such as the expandable member shown in FIG. 13B) in a wound configuration. The expandable member (1330) is depicted wound around a gear (1310) having one or more teeth (1312). While shown in FIG. 13C as a cylindrical gear (e.g., having a cylindrical body), the gear (1310) need not be so, and the gear body (1342) may have any suitable cross-sectional shape, such as, for example, oval, square, rectangular, etc. Each tooth (1312) may have a predetermined tapered (e.g., angled, curved) shape configured to facilitate even load transfer between the openings of the tracks (1332, 1334). The variable spacing and aperture geometry of the expandable member (1330) can facilitate precise winding of the expandable member around the gear (1310). In the wound configuration shown in FIG. 13C, the expandable member (1330) can include one or more overlapping layers (e.g., turns). For example, in a radially outward direction from the radial center of the wound expandable member (1330), the expandable member (1330) can include a first layer (1345) (the innermost layer), a second layer (1347), a third layer (1349), and a fourth layer (1351) (the outermost layer). The number of layers of the expandable member (1330) in a wound configuration can be based on at least the length and thickness of the expandable member, the diameter of the gear, the number of teeth, etc. The distance (1341, 1343) (e.g., spiral pitch) between adjacent openings (e.g., tracks) may increase (e.g., radially outward) from the first layer (1345) to the fourth layer (1351). The length (1341) of the openings (1332) may decrease (e.g., radially outward) from the first layer (1345) to the fourth layer (1351). This may allow the expandable member (1330) to be wrapped around the gear (1310) with minimal spacing between layers.Thus, the openings of the tracks (1332, 1334) may fit smoothly over and / or around the gear teeth (1312), while the portions of the expandable member (1330) between the tracks (1332, 1334) may fit smoothly around the body of the gear between the gear teeth (1312), which may reduce interference, binding, and bunching of the expandable member (1330) in the wound configuration.

[0120] In some variations, the expandable member (1330) (e.g., a circuit board, a flex circuit) can include an electrode array (not shown for clarity), which can include any of the electrode arrays described herein. For example, the electrode array can be disposed on an outer surface of the expandable member (1330).

[0121] In some variations, the distance (1341, 1343) between the openings of the tracks (1332, 1334) (e.g., spiral pitch) can be a function of the thickness of the expandable member (1330) and the number of turns (e.g., layers) of the expandable member (1330). For example, the expandable member (1330) can include one or more electrodes (e.g., electrode pads) of an electrode array (not shown in FIGS. 13A-13C) that can increase the thickness of those portions of the expandable member (1330). The length of the openings (1332, 1334) and / or the distance between adjacent openings can increase with increasing thickness of the expandable member (1330).

[0122] In some variations, the second elongate body (1312) (e.g., an internal torsion member, a rotatable member) can be configured to rotate relative to the first elongate body (1310) to transition the expandable member (1330) between a rolled configuration and a deployed configuration. In some of these variations, the expandable member (1330) can comprise a lumen having a diameter of at least 10 mm in the deployed configuration.

[0123] 14-29B show additional pulsed electric field device variations including an expandable member comprising an inflatable member (e.g., a balloon). FIG. 14A is a perspective view of a pulsed electric field device (1400) and visualization device (1450) variation. FIG. 14B is a cutaway perspective view of the pulsed electric field device (1400) and visualization device (1450) without the base layer (1430) and electrode array. In some variations, the pulsed electric field device (1400) may comprise a first elongate body (1410) comprising a lumen and a second elongate body (1420) positioned at least partially within the lumen of the first elongate body (1410). Multiple expandable members (1460) may be coupled to the first elongate body (1410). For example, multiple torus-shaped or spiral tube-shaped expandable members (1460) can be coupled in parallel to the first elongate body (1410). In some variations, the expandable members (1460) can be helical, spiral, and / or serpentine. For example, one or more of the expandable members (1460) can comprise one or more helices or coils. In these variations, the expandable members need not have inner or outer ends coupled to their respective elongate bodies. In some variations, the expandable members (1460) can comprise inflatable members.

[0124] In some variations, the expandable member (1460) may comprise a base layer (1430) (e.g., a circuit board, a flex circuit) that can be coupled to any of the electrode arrays described herein. For example, the electrode array (1430) can be disposed on an outer surface of the expandable member (1460). The second expandable member (1440) can optionally be coupled to the second elongate body (1420) and can be configured to dilate tissue and / or improve visualization of tissue within the body cavity. For example, the second expandable member (1440) can be concentrically coupled to the distal end of the second elongate body (1420). That is, the central longitudinal axis of the second expandable member (1440) can be coupled to the longitudinal axis of the second elongate body (1420). In some variations, the second expandable member (1440) can be an inflatable member, such as a balloon.

[0125] 14A and 14B illustrate a pulsed electric field device (1400) and a plurality of expandable members (1460) in an expanded or inflated configuration, where the expandable members (1460) are configured to engage tissue, such as the inner surface of the duodenum (not shown for clarity). In some variations, the expandable members (1460) may comprise a lumen having a diameter of at least 10 mm in the expanded configuration. In some variations, the plurality of expandable members (1460) may be configured to transition between a compressed configuration and an expanded configuration, such as a partially or semi-expanded configuration. In some variations, the expandable member (1600) in the expanded configuration may have a diameter of about 10 mm to about 50 mm, and about 15 mm to about 50 mm, including all ranges and subvalues ​​therebetween. A visualization device (1440) may be disposed within the lumen of the expandable member (1460) in the expanded configuration. In some variations, at least the proximal and distal ends of the second expandable member (1440) may be transparent, thereby allowing a visualization device (1450) to image through the second expandable member (1440).

[0126] 15A and 15B are cutaway perspective views of a variation of a pulsed electric field device (1500) and visualization device (1550) similar to those described in FIGS. 14A and 14B. As shown therein, the pulsed electric field device (1500) may include a first elongate body (1510) having a lumen therethrough and a second elongate body (1520) positioned at least partially within the lumen of the first elongate body (1510). Multiple expandable members (1560) may be coupled to the first elongate body (1510). For example, multiple torus-shaped expandable members (1560) may be coupled in parallel to the first elongate body (1510).

[0127] In some variations, the expandable member (1560) may include an electrode array (not shown for clarity), which may include any of the electrode arrays described herein. For example, the electrode array may be disposed on or coupled to the outer surface of the expandable member (1560). The second expandable member (1540) may be coupled to the second elongate body (1520). For example, the second expandable member (1540) may be concentrically coupled to the distal end of the second elongate body (1520). That is, the central longitudinal axis of the second expandable member (1540) may be coupled to the longitudinal axis of the second elongate body (1520). In some variations, the second expandable member (1540) may be an inflatable member, such as a balloon. A visualization device (1540) may be disposed within the lumen of the expandable member (1560) in the expanded configuration. In some variations, at least the proximal and distal ends of the second expandable member (1540) may be transparent, thereby allowing a visualization device (1550) to image through the second expandable member (1540).

[0128] 16 is a perspective view of variations of a pulsed electric field device (1600) and a visualization device (1650). In some variations, the pulsed electric field device (1600) may include a first elongate body (1610) having a lumen therethrough and a second elongate body (1620) positioned at least partially within the lumen of the first elongate body (1610). An expandable member (1630) may be coupled to the first elongate body (1610). In some variations, the expandable member (1630) may include an electrode array (not shown for clarity), which may include any of the electrode arrays described herein. For example, the electrode array may be disposed on or coupled to an outer surface of the expandable member (1630). The expandable member (1630) may include a lumen formed by longitudinally joining the outer wall of the expandable member (1630) to the inner wall of the expandable member (1630) and a plurality of elongated recesses (1632). For example, the elongated recesses (1632) may be pleated to control the inner and outer diameters of the expandable member (1630). This configuration may aid in the expansion of the expandable member (1630) that includes an electrode array (not shown for clarity). For example, one or more electrodes may be disposed on the expandable member (1630) between the elongated recesses (1632).

[0129] The second expandable member (1640) can be coupled to the second elongate body (1620). For example, the second expandable member (1640) can be offset relative to the longitudinal axis of the second elongate body (1620). For example, a sidewall of the second expandable member (1640) can be coupled to the distal end of the second elongate body (1620). In some variations, the second expandable member (1640) can be an inflatable member such as a balloon. The visualization device (1640) can be disposed within the lumen of the expandable member (1640) in the expanded configuration.

[0130] In some variations, the expandable member (1630) can be concentrically coupled to the first elongate body (1610). In some variations, the first elongate body (1610) can be coupled to a sidewall of the expandable member (1630). In some variations, the second expandable member (1640) can be coupled to the second elongate body (1620) and disposed distally of the expandable member (1630). In some variations, the visualization device (1650) can be disposed within the lumen of the expandable member (1630). In some variations, at least the proximal and distal ends of the second expandable member (1640) can be transparent, thereby allowing the visualization device (1650) to image through the second expandable member (1640). In some variations, the multiple electrodes can comprise multiple parallel elongate electrodes, as described in more detail herein. Additionally or alternatively, the plurality of elongate electrodes may comprise an interdigitated configuration, for example, the plurality of elongate electrodes may comprise a curved shape (e.g., S-shaped, W-shaped).

[0131] In some variations, the pulsed electric field device may include a predetermined length of expandable member and / or electrode array for ablating a predetermined length of tissue. Figures 17 and 18 are perspective views of variations of pulsed electric field devices (1700, 1800) and visualization devices (1750, 1850) similar to Figures 16A and 16B but having multiple expandable members (1730, 1830). The spacing between the multiple expandable members (1730, 1830) may determine the degree to which the distal ends of the devices (1700, 1800) can bend. For example, the device (1700) may have greater flexibility than the device (1800) due to the greater distance between the expandable members (1730).

[0132] In some variations, the pulsed electric field device (1700, 1800) may include a first elongate body (1710, 1810) having a lumen therethrough and a second elongate body (1720, 1820) positioned at least partially within the lumen of the first elongate body (1710, 1810). A plurality of expandable members (1730, 1830) may be coupled to the first elongate body (1710, 1810). In some variations, the expandable members (1730, 1830) may include an electrode array (not shown for clarity), which may include any of the electrode arrays described herein. A second expandable member (1740, 1840) may be coupled to the second elongate body (1720, 1820). For example, the second expandable member (1740, 1840) is offset relative to the longitudinal axis of the second elongate body (1620). In some variations, the second expandable member (1740) may be an inflatable member such as a balloon. The visualization device (1640) may be disposed within the lumen of the expandable member (1640) in the expanded configuration. At least proximal and distal portions of the expandable members (1740, 1840) may be transparent.

[0133] In some variations, the pulsed electric field device may include an expandable member comprising a transparent inflatable member. FIG. 19 is a perspective view of a variation of a pulsed electric field device (1900) and a visualization device (1940). In some variations, the pulsed electric field device (1900) may include an elongate body (1910), and an expandable member (1920) may be coupled to the elongate body (1910). In some variations, the expandable member (1920) may include an electrode array (1930), which may include any of the electrode arrays described herein. For example, the electrode array may be disposed on or coupled to an outer surface of the expandable member (1920). At least a proximal and distal portion of the expandable member (1920) may be transparent to allow a visualization device (1940) to visualize through the expandable member (1920). In some variations, the expandable member (1920) may be concentrically coupled to the distal end of the elongate body (1920). That is, the central longitudinal axis of the expandable member (1920) may be aligned with and may be the same as the longitudinal axis of the elongate body (1910).

[0134] FIG. 20 is a perspective view of a variation of a pulsed electric field device (2000) and visualization device (2040) similar to FIG. 19 , further comprising a second expandable member (2050) disposed distal to the expandable member (2020). The second expandable member (2050) can be configured to dilate tissue. The second expandable member (2050) can be an expandable member such as a balloon. In some variations, the pulsed electric field device (2000) can comprise an elongate body (2010), and the expandable member (2020) can be coupled to the elongate body (2010). In some variations, the expandable member (2020) can comprise an electrode array (2030), which can comprise any of the electrode arrays described herein. At least the proximal and distal portions of the expandable member (2020) can be transparent.

[0135] FIG. 21 is a perspective view of a variation of a pulsed electric field device (2100) and visualization device (2150) similar to FIG. 20 but having multiple expandable members (2130) proximal to a distal second expandable member (2140) (e.g., inflatable member). The spacing between the multiple expandable members (2130) can determine the degree to which the distal end of the device (2130) can bend. In some variations, the pulsed electric field device (2100) can include an elongate body (2110), and the multiple expandable members (2130) can be coupled to the elongate body (2110). In some variations, the multiple expandable members (2120) can include an electrode array (2130), which can include any of the electrode arrays described herein. At least the proximal and distal portions of the expandable member (2120) can be transparent.

[0136] Figure 22 is a perspective view of a variation of a pulsed electric field device (2200) and visualization device (2250) similar to Figure 19, but in which the side walls of an expandable member (2220) and a second expandable member (2240) are attached to an elongate body (2210). This may aid in visualization through the device (2200) by the visualization device (2250), as the visualization device (2250) may be aligned with the center of the expandable member (2220). In some variations, the expandable member (2220) may include an electrode array (2230), which may include any of the electrode arrays described herein. At least the proximal and distal portions of the expandable member (2220) may be transparent.

[0137] Figure 23 is a perspective view of a variation of a pulsed electric field device (2300) and visualization device (2340) similar to Figure 19, but in which the side walls of an expandable member (2320) and a second expandable member (2330) are attached to an elongate body (2310). This may aid in visualization through the device (2300) by the visualization device (2340), as the visualization device (2340) may be aligned with the center of the expandable member (2320). In some variations, the expandable member (2320) may include an electrode array (not shown), which may include any of the electrode arrays described herein. At least the proximal and distal portions of the expandable member (2320) may be transparent.

[0138] FIG. 24 is a perspective view of a variation of a pulsed electric field device (2400) and visualization device (2450) similar to FIG. 21 but having an expandable member (2420) and a sidewall of a second expandable member (2440) (e.g., an inflatable member) attached to an elongate body (2410). In some variations, the pulsed electric field device (2400) may include an elongate body (2410), and multiple expandable members (2420) may be coupled to the elongate body (2410). In some variations, the multiple expandable members (2420) may include an electrode array (2430), which may include any of the electrode arrays described herein. At least proximal and distal portions of the multiple expandable members (2420) may be transparent. The spacing between the multiple expandable members (2420) may determine the degree to which the distal end of the device (2400) bends.

[0139] FIG. 25 is a perspective view of a variation of a pulsed electric field device (2500) and visualization device (2540) similar to FIG. 23, but in which an expandable member (2530) is concentrically coupled to the distal end of a first elongate body (2520). That is, the central longitudinal axis of the expandable member (2530) may be aligned with and may be the same as the longitudinal axis of the elongate body (2520). Similarly, a second expandable member (2330) (e.g., an inflatable member) is concentrically coupled to the distal end of a second elongate body (2510) that is at least partially disposed within the lumen of the first elongate body (2520). In some variations, the expandable member (2530) may comprise an electrode array (not shown), which may comprise any of the electrode arrays described herein. At least the proximal and distal portions of the expandable member (2530) may be transparent.

[0140] FIG. 26 is a perspective view of a variation of a pulsed electric field device (2600) and visualization device (2650), similar to FIG. 21, but bent to demonstrate the flexibility of the device (2600). The spacing between the plurality of expandable members (2620) can determine the degree to which the distal end of the device (2600) can bend. In some variations, the pulsed electric field device (2600) can include an elongate body (2610), and the plurality of expandable members (2620) can be coupled to the elongate body (2610). In some variations, the plurality of expandable members (2620) can include an electrode array (2630), which can include any of the electrode arrays described herein. At least the proximal and distal portions of the plurality of expandable members (2620) can be transparent. A second expandable member (2610) can be attached to the elongate body (2610) proximal to the plurality of expandable members (2620).

[0141] Figure 27 is a variation of a pulsed electric field device (2700) and visualization device (2750) similar to Figure 24. For example, the sidewalls of each expandable member (2720) and second expandable member (2740) can be attached to an elongate body (2710). In some variations, the plurality of expandable members (2720) can comprise an electrode array (2730), which can comprise any of the electrode arrays described herein. At least the proximal and distal portions of the plurality of expandable members (2720) can be transparent. The spacing between the plurality of expandable members (2720) can determine the degree to which the distal end of the device (2700) can bend.

[0142] FIG. 28A is a perspective view of a variation of the expandable member (2810) of a pulsed electric field device (2800) and a visualization device (2830). FIGS. 28B-28E are perspective views of the pulsed electric field device (2800) and the visualization device (2830). As shown therein, in some variations, the pulsed electric field device (2800) may comprise a releasable elongate body (2840) and an expandable member (2810) coupled to the elongate body (2840). The expandable member (2810) may comprise a lumen, a compressed configuration, a semi-expanded configuration, and an expanded configuration. The expandable member (2810) may further comprise an electrode array (2820). The lumen of the expandable member can be configured to releasably couple to the visualization device (2830). In some variations, the lumen defines a central longitudinal axis of the expandable member (2830). The elongate body (2840) can be configured to provide one or more of power to the electrode array (2820) and fluid to the expandable member (2810) for expansion and compression. As used herein, fluid refers to a liquid, a gas, or a combination thereof. For example, in some variations, gases commonly used in interventional procedures, such as CO2 and / or air, can be used.

[0143] In Figures 28A and 28C, the visualization device (2830) is disposed within the lumen of the expandable member (2810), allowing the visualization device (2830) to translate the expandable member (2810) through one or more body cavities. Figure 28B shows the visualization device (2830) decoupled (e.g., disconnected, separated) from the expandable member (2830). This may allow the visualization device (2830) to, for example, image a proximal portion of the expandable member (2810) and navigate independently of the expandable member (2830). After energy delivery is complete, the visualization device (2830) can be recoupled to the expandable member (2830) and withdrawn from the patient. In Figure 28D, the visualization device (2830) has been further advanced relative to the expandable member (2810) so that the distal end of the visualization device (2830) can bend. In some variations, as shown in Figure 28E, the visualization device (2830) can bend within the lumen of the expandable member (2810).

[0144] FIG. 29A is a perspective view similar to FIGS. 28A-28E, but of a variation of a pulsed electric field device (2900) and visualization device (2930) having multiple expandable members (2910). The spacing between the multiple expandable members (2910) can determine the degree to which the distal end of the device (2900) can bend. In some variations, the multiple expandable members (2910) can include an electrode array (2920), which can include any of the electrode arrays described herein. FIG. 29B is a perspective view of the pulsed electric field device (2900) and visualization device (2930) detached (e.g., disconnected, separated) from the multiple expandable members (2910) shown in FIG. 29A.

[0145] FIG. 30A is a perspective view of a variation of a pulsed electric field device (3000) comprising an expandable member (3010) (e.g., inflatable member) comprising an electrode array (3020). In some variations, the expandable member (3010) may comprise a base layer (e.g., circuit board, flex circuit) that can be coupled to any of the electrode arrays described herein. For example, the electrode array (3020) may be disposed on an outer surface of the expandable member (3010). The electrode array (3020) may comprise a plurality of substantially parallel elongated electrodes arranged circumferentially about the longitudinal axis of the expandable member. The expandable member (3010) of FIG. 30A is shown in an expanded configuration. FIG. 30B is a perspective view of the pulsed electric field device (3000) of FIG. 30A positioned within a tissue lumen (3030). The expandable member (3010) in Figure 30A is shown in an expanded configuration such that the electrode array (3020) contacts the tissue lumen (3030).

[0146] 31 is a perspective view of a variation of a pulsed electric field device (3100) comprising an expandable member (3110) (e.g., inflatable member) comprising an electrode array (3122). The electrode array (3122) may comprise a helical shape including predetermined turns. In some variations, the expandable member (3110) may comprise a base layer (e.g., a circuit board, a flex circuit) that can be coupled to any of the electrode arrays described herein. For example, the electrode array (3122) may be disposed on an outer surface of the expandable member (3110).

[0147] FIG. 32 is a perspective view of a variation of a pulsed electric field device (3200) comprising a visualization device (3230) coupled to an expandable member (3210) comprising an electrode array (3220). The expandable member (3210) may comprise a stent-like structure that can be configured to transition between a compressed configuration and an expanded configuration. For example, the expandable member (3210) can change configuration by one or more of a change in length and a helical rotation. In some variations, the expandable member (3210) may comprise a base layer (e.g., a circuit board, a flex circuit) that can be coupled to any of the electrode arrays described herein. For example, the electrode array (3220) can be disposed on an outer surface of the expandable member (3210). The electrode array (3220) may comprise a plurality of substantially parallel elongated electrodes arranged circumferentially about the longitudinal axis of the expandable member. Additionally or alternatively, the plurality of elongated electrodes may comprise an interdigitated configuration. The expandable member (3210) of Figure 32 is shown in an expanded configuration. The expandable member (3210) may include a lumen configured to receive a visualization device (3230). Figures 33A and 33B are side and perspective views, respectively, of an expandable member (3310) similar to the pulsed electric field device (3200) of Figure 32.

[0148] Electrode array Generally, the electrodes and electrode arrays described herein can be configured to treat tissue, such as duodenal tissue, of a patient. In some variations, the electrode array can engage the duodenum and be energized to treat a predetermined portion of the tissue to resurface the duodenum. For example, the tissue can undergo cell lysis using PEF energy during a treatment procedure. PEF energy tissue treatment can be delivered uniformly at a predetermined depth (e.g., about 1 mm) to quickly and precisely treat the tissue without causing significant damage to surrounding (e.g., deeper) tissue.

[0149] In some variations, tissue treatment properties can be controlled by the size, shape, spacing, composition, and / or geometry of the electrode array. For example, the electrode array can be flexible to conform to a non-planar tissue surface. In some variations, the electrode array can be embossed or reflowed to form a non-planar electrode surface. In some variations, the electrode array can include a tissue contacting layer. In some variations, the tissue contacting layer can function as a salt bridge between the electrode and the tissue. In some variations, the electrode array can include a hydrophilic coating. In some variations, the electrode array can be divided into subarrays to reduce drive current requirements.

[0150] In some variations, raised and / or rounded (e.g., semi-ellipsoidal) electrodes generally promote more reliable contact with tissue than flat electrodes, thus promoting a more uniform electric field and improved therapeutic outcomes. For example, tissue contact (e.g., apposition) with the electrode completes the electrical circuit during energy delivery, thus providing resistance within the circuit for uniform electric field distribution. Raised and / or rounded (e.g., semi-ellipsoidal) electrodes may reduce sharp edges and arcing. Spaced electrodes in an electrode array may further reduce ion concentration and associated electrolysis. The electrode array configurations (e.g., arrangement, spacing, shape, size) shown and described herein provide uniformly spaced electrodes that allow the corresponding expandable member to repeatedly expand and compress.

[0151] In some variations, one or more of the electrodes (e.g., a plurality of electrodes, a portion of the electrodes in an array, all of the electrodes in an array) may comprise one or more biocompatible metals such as gold, titanium, stainless steel, nitinol, palladium, silver, platinum, combinations thereof, etc. In some variations, one or more of the electrodes (e.g., a plurality of electrodes, a portion of the electrodes in an array, all of the electrodes in an array) may comprise an atraumatic (e.g., blunt, rounded) shape such that the electrodes do not puncture tissue when pressed against it. For example, the electrode array may engage the inner circumference of the duodenum.

[0152] In some variations, the electrode array can be connected to the signal generator by one or more leads (e.g., conductors). For example, the leads can extend through an elongate body (e.g., an outer catheter, an outer elongate body) to the electrode array. One or more portions of the leads can be insulated (e.g., PTFE, ePTFE, PET, polyolefin, parylene, FEP, silicone, nylon, PEEK, polyimide). The leads can be configured to maintain a predetermined electrical potential without breakdown of the corresponding insulator.

[0153] In some variations, the electrode array may comprise multiple elongated electrodes in a substantially parallel or interdigitated configuration. The electrode array shapes and configurations described herein may generate an electric field of a predetermined strength (e.g., about 400 V / cm to about 7,500 V / cm) at a predetermined tissue depth (e.g., about 0.7 mm, about 1 mm) without excessive heat, breakdown, steam generation, etc. In contrast, some electrode configurations have a shape (e.g., radius of curvature) that allows the generated electric field to rapidly decrease without the application of very high voltages (e.g., thousands of volts) that can lead to the aforementioned excessive heat, breakdown, and steam generation.

[0154] FIG. 34A is a perspective view of a variation of an electrode array (3400) comprising multiple elongated electrodes (3410) on a substrate (3420). In some variations, at least one of the electrodes (3410) may have a semi-elliptical cross-sectional shape. In some cases, all of the electrodes (3410) in the electrode array (3400) may have a semi-elliptical cross-sectional shape. Generally, the electric field is strong near the points and edges of the electrodes due to concentrated surface charge on the electrodes. Sharp-edged electrodes and high electric fields can generate one or more of electrical discharges (e.g., arcing), high heat (e.g., boiling), high current densities (e.g., electrolysis), and gas bubbles. The semi-elliptical cross-sectional shapes described herein can reduce one or more of these effects compared to sharp-edged electrodes. In some variations, the major axis of the electrode (3410) is twice the electrode width, and the minor axis of the electrode is equal to the electrode height at the center of the electrode.

[0155] The electrode arrays described herein can be formed using any suitable manufacturing technique. For example, as shown in Figure 37, in some variations, the electrode array (3700) can be formed by pressing the electrode array (3700) between a pair of embossing dies (3750) to form a plurality of spaced-apart round electrodes. The electrode arrays described herein can be fabricated using any suitable technique, including, but not limited to, deposition of solder or other metals, dimples on a substrate, plating of metals (e.g., gold), and lamination.

[0156] In some variations, additional layers and / or coatings may be applied to the electrodes. For example, the electrode array (3800) illustrated in Figure 38 may exhibit a tissue-contacting layer (3810), as further described herein.

[0157] If the edges of a flat electrode are 2d apart (the width of the electrode), then the equivalent electric field is provided by an elliptical conductor with height h (minor axis) and width 2w (where w is the major axis), with the foci of the ellipse d from the center. The eccentricity can be given by equation (2): ε=(1+(h / d) 2 ) -1 / 2 Formula (2)

[0158] The footprint of a raised electrode is 2w=2d / ε, increasing by a factor of 1 / 2ε from a flat electrode. When raised or solder-reflowed electrodes are used, they will generally have some mechanical resistance to bending around a centerline other than one parallel to the electrode.

[0159] In some variations, the drive voltage applied to the electrode array may depend at least on the spacing between the electrodes of the electrode array as well as the dimensions of the electrodes. For example, relatively wide, elongated electrodes may reduce the effects of strong electric field strength at sharp, curved edges. In some variations, the electrode array may be configured in multiple sets (e.g., groups, zones) to assist in energy delivery for a treatment procedure. For example, the electrode array may include multiple zones arranged along the length of the expandable member. The multiple zones may be activated, for example, in a predetermined sequence.

[0160] 34B is a cross-sectional side view of an electrode array (3400). In some variations, the electrode array may comprise a plurality (e.g., 4, 8, 12, 16, 20, 24, 30, and any range therein) of elongated electrodes. For example, the electrode array may comprise more than about six electrodes. In some variations, the plurality of elongated electrodes may comprise a ratio of the center-to-center distance between adjacent (i.e., immediately adjacent) electrodes and the electrode width (3414) of about 2.3:1 to about 3.3:1, and about 2.8:1 to about 3.0:1. For example, the distance (3412) between adjacent electrodes (3410) may be about 1 mm to about 1.8 mm, the width (3414) of the electrodes (3410) may be about 0.6 mm to about 1.8 mm, and the height (3416) of the electrodes (3410) may be about 0.15 mm to about 0.5 mm, including all values ​​and subranges therebetween, such as about 0.3 mm. In some variations, the plurality of elongated electrodes comprises a center-to-center distance between adjacent electrodes of less than about 10 mm, less than about 7 mm, and less than about 5 mm, including all values ​​and subranges therebetween. In some variations, the plurality of elongated electrodes may comprise a first electrode and a second electrode parallel to the first electrode. Additionally or alternatively, the plurality of electrodes may comprise an interdigitated configuration. In some variations, the center-to-center distance between adjacent electrodes and the width of the plurality of elongated electrodes may be substantially equal.

[0161] In some variations, adjacent electrodes may be separated by a weighted average distance of about 0.3 mm to about 6 mm. The weighted average distance may be defined as follows: Each electrode in the plurality of elongated electrodes has coordinates s(xi ,y i ) (Equation 3), where x and y are parallel to the surface of the electrode array and the first distance (s + ) is parallel to the nearest electrode of a first polarity (e.g., positive polarity), and a second distance (s) is parallel to the nearest electrode of a second polarity opposite the first polarity (e.g., negative polarity). The weighted average distance (S) may be given by equation (4):

number

number

[0162] In some variations, the ratio of electrode height to electrode width may be about 1:4 to about 1:8. In some variations, the surface area of ​​the plurality of electrodes may comprise about 20% to about 75% of the surface area of ​​the electrode array, including all ranges and subvalues ​​therebetween. In some variations, the surface area of ​​the plurality of electrodes comprises about 20% to about 45% of the surface area of ​​the expandable member in a given configuration, including all ranges and subvalues ​​therebetween. In some variations, the electrode array may comprise conductors that are about 36% by area. In some variations, the surface area of ​​the plurality of electrodes comprises about 4% to about 30% of the surface area of ​​the duodenum, including all ranges and subvalues ​​therebetween. A typical duodenum has a circumference of about 20 mm to about 45 mm, a length of about 25 mm to about 35 mm, and a length of about 700 mm. 2 ~approx. 1850mm 2 and a surface area of

[0163] In some variations, the electrode array may include multiple groups of electrodes (e.g., see zones A, B, and C in FIG. 51), each of which may be activated in a predetermined sequence. In some variations, more uniform treatment of tissue (e.g., in areas where electrode groups intersect) may be achieved by decreasing the width of the most peripheral electrodes of each group and decreasing the distance between those electrodes. In some variations, more uniform treatment of tissue (e.g., in areas where electrode groups intersect) may be achieved by interdigitating the most peripheral electrodes of each group to overlap the treatment area.

[0164] As described in detail herein, a pulsed electric field device may include an expandable member having a compressed (e.g., coiled) configuration and an expanded (e.g., deployed) configuration. In some variations, the expandable member may include or be otherwise formed from an electrode array (e.g., multiple electrodes). In some variations, the expandable member may include a flex circuit comprising multiple electrodes. FIG. 34C is a perspective view of an exemplary variation of an expandable member comprising an electrode array (3400). The electrode array (3400) may include multiple elongated electrodes (3410) on a substrate (3420). In some variations, the electrode array (3400) may be in the form of a flex circuit. As shown therein, the flex circuit may include the electrode array (3400) or multiple electrodes, for example, multiple elongated parallel electrodes. The expandable member is illustrated in an expanded, cylindrical configuration in FIG. 34C.

[0165] Figure 35 is an electric field intensity plot for electrode arrays having the electrode spacing to electrode width ratios described herein. As can be seen, these electrode arrays produce a substantially uniform electric field. The pulsed or modulated electric field can vary spatially by up to about 20% at a given treatment distance from the electrode array. For example, the electric field (3520) produced by electrode (3510) can vary spatially by up to about 20% at a distance of about 0.7 mm from the electrode array (within the submucosal layer of tissue in contact with the electrode array). This can improve consistency in energy delivery and treatment results.

[0166] Figure 80A is an electric field intensity plot (8000) of variations of an electrode array (8010). In some variations, the electrode array (8010) can be configured to generate a substantially uniform electric field (8020) across its entire surface at a predetermined tissue treatment depth (8030). For example, the predetermined tissue depth can be configured to receive a voltage field of approximately 2500 V / cm. A current of approximately 50 A and a voltage of approximately 600 V at a frequency of approximately 350 kHz can be applied to the electrodes. This can improve consistency of energy delivery and treatment results.

[0167] 80B is an electric field intensity plot (8100) of variations of the electrode array (8110). In some variations, the electrode array (8110) can be configured to generate a substantially uniform electric field (8120) at a first predetermined tissue treatment depth (8130) with an electric field magnitude below the treatment threshold at a second predetermined tissue depth (8140). For example, the electrode array (8110) can receive a voltage of approximately 600 V and generate an electric field (8120) below the treatment threshold at a tissue depth of approximately 1.48 mm.

[0168] In some variations, the tissue treatment depth (e.g., mm) receiving a voltage field of approximately 2500 V / cm may depend on the electrode configuration and the voltage applied to the electrode array. For example, tissue treatment may require approximately 2,000 V / cm, in which case the table values ​​would be adjusted for deeper tissue treatment at the same applied voltage. The current may depend on the tissue conductivity and electrode configuration. Assuming a constant voltage, the penetration of the electric field is also constant. The tissue treatment rate may depend on the state of the tissue during treatment (e.g., stretched, compressed, in contact with the electrodes). The tissue treatment depth may depend on one or more of the tissue treatment rate, current, effective voltage, and tissue type. Table 1 below provides an example variation of a set of parameters (e.g., voltage, current, power) configured to provide a predetermined ratio of voltage field depth to tissue treatment depth. [Table 1]

[0169] Figure 36 is an electric field strength plot of a conventional electrode array lacking electric field uniformity. The electrodes (3610) are shaped and spaced such that the generated electric field (3620) provides an electric field strength of up to about 200 V / cm to some portions of the submucosal tissue, while other portions receive little, if any, of the electric field (3620). Similarly, an electric field strength of up to about 1000 V / cm is provided to some portions of the mucosa, while other portions receive little, if any, of the electric field (3620). Thus, with conventional electrodes, even if a given amount of energy is delivered to some portions of the tissue, the inconsistent energy delivery has limited positive impact on treatment outcomes.

[0170] In some variations, the electrode arrays described herein may further comprise a tissue contact layer. The tissue contact layer may be provided between the electrode and tissue to improve electrical conduction and reduce burning due to current crowding at the ends of the electrodes. Figure 38 is a schematic cross-sectional view of an exemplary variation of an electrode array (3800) comprising a tissue contact layer (3810). The electrode array (3800) may be formed by a pair of embossing dies (e.g., die (3750)) that form a plurality of spaced-apart round electrodes (e.g., embossed dimples).

[0171] FIG. 39 is a schematic cross-sectional view of an electrode array (3900) including a tissue contacting layer (3920) and in contact with tissue (3910) (e.g., the duodenum). In some variations, the tissue contacting layer (3920) can be disposed on the electrode and / or electrode array substrate. The tissue contacting layer (3920) can have a lower conductivity than the electrode. In some variations, the conductivity of the tissue contacting layer can be about 0.03 S / m to about 0.9 S / m, about 0.03 S / m to about 0.3 S / m, and about 0.01 S / m to about 0.7 S / m, including all ranges and subvalues ​​therebetween. In some variations, the tissue contacting layer can have a thickness of about 10% to about 20% of the width of the electrode. In some variations, the tissue contacting layer can be composed of an ohmic electrical conductor, such as carbon particle-loaded rubber, or a porous material, such as an open-cell sponge, with an ionic conductor, such as sodium chloride or carbon.

[0172] In some variations, the portion of the tissue-contacting layer disposed between the electrodes and / or on the edges of the electrodes may have a thickness of about 0.02 mm to about 0.08 mm and a conductivity of about 0.02 S / m to about 0.4 S / m, including all ranges and subvalues ​​therebetween. The tissue-contacting layer disposed on the electrode edges can reduce heating by reducing current draw in high field strength portions of the electrode. For example, this portion of the tissue-contacting layer may comprise carbon black disposed in a polymer matrix (e.g., acrylic). For example, one or more electrode edges may comprise a tissue-contacting layer (e.g., carbon black) having a thickness of about 0.02 mm to about 0.05 mm and a conductivity of about 0.02 S / m to about 0.4 S / m. Carbon black may improve the performance of the electrode array by absorbing ultraviolet energy and reducing sparkover.

[0173] In some variations, the electrode array may further comprise a hydrophilic layer disposed on the electrodes and / or substrate to improve the gliding of the pulsed electric field device relative to tissue. Similarly, the dilator or any component of the pulsed electric field device may comprise a hydrophilic layer to improve the gliding of the pulsed electric field device relative to tissue.

[0174] 40 is a schematic cross-sectional side view of an exemplary variation of an electrode array (4000). To uniformly treat tissue at a predetermined treatment distance from the electrode (4000), z along the ) and above the space between the electrodes (e.g., E x It may be beneficial for the electric field strength (along the

[0175] 41A-41D are electric field strength plots of exemplary electrode array variations showing how the ratio of center-to-center electrode spacing to electrode width affects electric field strength uniformity. For treatment depths of 1 mm or less, a ratio of 2:1 (FIG. 41A) may produce a non-uniform electric field, while ratios of about 2.3:1 to about 3.3:1, and about 2.8:1 to about 3.0:1 (FIGS. 41B-41D) may produce a substantially uniform electric field. For example, at a treatment depth of about 0.7 mm, the E in FIG. x and E z The difference is significantly larger than in either of FIGS. 41B to 41C.

[0176] Figure 42 shows a histogram of the total field strength of the electrode array at a treatment depth of about 0.7 mm and twice that depth, about 1.4 mm. At that treatment depth, there is a spread of about 5% at a dose of about 3,100 V / cm. At twice that treatment depth, there is a spread of less than 2% at a dose of about 1,550 V / cm. Thus, the pulsed or modulated electric field energy is delivered substantially uniformly to a given tissue depth.

[0177] In some variations, the pulsed electric field systems disclosed herein may include a return electrode for drawing PEF current from the patient. In some variations, the catheter (e.g., the third elongate body) may include the return electrode. In some variations, the return electrode may be external to the patient and in contact with the patient (e.g., a skin patch electrode, a grounding pad). For example, a set of return electrodes may be disposed on the patient's back to allow current to flow from the electrode array through the patient and then to the return electrode. For example, one or more return electrodes may be disposed on the patient's skin. To improve contact, a conductive gel may be applied between the return electrode and the skin.

[0178] Figure 76 is a perspective view of a variation of an expandable member (e.g., an electrode array) (7600) in a partially deployed or expanded configuration. The electrode array (7600) may comprise a plurality of elongated electrodes (7610) on a substrate (7620). In some variations, the substrate (7620) may comprise a flex circuit comprising a plurality of electrodes. The electrode array (7600) may comprise a plurality of elongated electrodes (7610) on the substrate (7620). As shown therein, the flex circuit may comprise the electrode array (7600) or a plurality of electrodes, for example, a plurality of elongated parallel electrodes.

[0179] In some variations, the substrate (7620) of the electrode array (7600) may define one or more openings (7630) (e.g., fluid openings) between adjacent electrodes (7610) configured to generate suction (e.g., negative pressure) and / or output fluid (e.g., saline). The use of suction or negative pressure applied through the openings can draw tissue toward the electrode array (7600) and facilitate contact between the tissue and the electrode array (e.g., increase the contact area between the tissue surface and the electrode surface). For example, the electrode array (7600) can engage the duodenum via suction through one or more openings (7630), which can promote more reliable (e.g., consistent) electrical contact between the pulsed electric field device and the tissue, thus promoting a more uniform electric field and improved treatment results. In some variations, multiple openings (7630) (e.g., rows of openings (7630)) can be disposed between each pair of adjacent electrodes (7610) at predetermined intervals. For example, the openings (7630) can be spaced along the length of the electrodes (6920). In some variations, the fluid openings (7630) can be disposed closer to one of the electrodes (7610) to promote contact between tissue and at least one of the electrodes (7610). Additionally or alternatively, the openings (7630) can be equally spaced between adjacent electrodes (7610).

[0180] Additionally or alternatively, the openings (7630) can be configured for fluid irrigation. The electrode array (7600) can be in fluid communication with (e.g., fluidly coupled to) a fluid source (not shown) for fluid irrigation. For example, fluid can be removed from (e.g., aspirated from) the body cavity after applying a pulsed or modulated electric field using the electrodes (7610). In some variations, removal of fluid can facilitate apposition and / or contact of tissue with the electrode array (7600).

[0181] In some variations, at least one of the electrodes (7610) may have a semi-elliptical cross-sectional shape. In some cases, all of the electrodes (7610) in the electrode array (7600) may have a semi-elliptical cross-sectional shape. In some variations, the major axis of the electrode (7610) may be approximately twice the electrode width, and the minor axis of the electrode may be approximately equal to the electrode height at the center of the electrode.

[0182] FIG. 77 is a perspective view of an exemplary variation of a pulsed electric field device (7700) in an expanded configuration configured to engage tissue, such as the inner surface of the duodenum (not shown). The pulsed electric field device (7700) may comprise a first elongate body (7710), a second elongate body (7720), an expandable member (7730), and dilators (7760, 7762). In the expanded or deployed configuration, the expandable member (7730) may have a generally elliptical or cylindrical shape, with a second inner diameter and a second outer diameter having predetermined diameters greater than the first inner diameter and the first outer diameter, respectively. The expandable member (7730) in the expanded configuration may have a predetermined flexibility configured to conform to the shape of the tissue it engages. The expandable member (7730) may comprise, for example, the electrode array (7600) shown in FIG. 76.

[0183] In some variations, the first and second elongate bodies (7710, 7720) can be configured to rotate axially relative to one another to transition the expandable member (7730) between a compressed configuration, an expanded configuration, and a semi-expanded configuration therebetween. For example, the second elongate body (7720) (e.g., an internal torsion member, rotatable member) can be rotatably positioned within the lumen of the first elongate body (7710), such that rotation of the second elongate body (7720) relative to the first elongate body (7710) transitions the expandable member (7730) between a rolled configuration and a deployed configuration. In some of these variations, the inner diameter of the lumen (7750) of the expandable member (7730) can be at least about 8 mm, at least about 10 mm, or between about 8 mm and about 10 mm in the deployed configuration, inclusive of all values ​​and subranges therebetween. As described in more detail herein, a visualization device (not shown) can be disposed within the lumen (7750) of the expandable member (7730) to assist in visualization. It should be understood that the pulsed electric field device (7700) can be advanced next to the visualization device and / or over a guidewire. In some variations, the visualization device can be used to guide advancement and visualize the treatment procedure such that a guidewire and / or other visualization modalities (e.g., fluoroscopy) are not required.

[0184] In some variations, the expandable member (7730) can be configured to transition between a compressed configuration and an expanded configuration. For example, the expandable member (7730) can transition to a partially expanded or semi-expanded configuration (between the compressed and expanded configurations) to allow a visualization device (e.g., an endoscope) to be disposed within the lumen of the expandable member (7730). In some variations, the inner surface of the expandable member can engage and retain the visualization device in the semi-expanded configuration.

[0185] FIG. 78A is an image of a pulsed electric field device (7800) in a compressed configuration, and FIG. 78B is a detailed image of the deployed electrode array (7800) of the pulsed electric field device shown in FIGS. 77 and 78A. The electrodes shown in FIGS. 76-78B may have a generally hemispherical shape, as described herein. In some variations, one or more of the electrodes of the electrode array (7610) may have a height of about 0.07 mm to about 0.38 mm, to about 0.178 mm, inclusive of all ranges and subvalues ​​therebetween. In some variations, the distance between adjacent (e.g., nearby) electrodes (7610) may be about 1.0 mm to about 1.4 mm, to about 1.2 mm, inclusive of all ranges and subvalues ​​therebetween. In some variations, one or more of the electrodes of the electrode array (7610) may have a pad width of about 0.5 mm to about 0.7 mm, to about 0.6 mm, inclusive of all ranges and subvalues ​​therebetween. In some variations, the distance between the electrode (7610) and the temperature trace (not shown) may be about 1.0 mm to about 1.4 mm, about 1.2 mm, including all ranges and subvalues ​​therebetween.

[0186] 43 is a perspective view of an exemplary variation of an expandable member (4300) comprising an electrode array (4310) comprising a plurality of spaced-apart, semi-elliptical electrodes. The semi-elliptical electrodes may form a plurality (e.g., 4, 8, 12, 16, 20, or any value therebetween) of parallel or interdigitated lines. Additionally or alternatively, the semi-elliptical electrodes may be raised relative to the substrate of the electrode array and may comprise a rounded or hemispherical shape. In some variations, the electrode array may comprise a tissue-contacting layer disposed over one or more of the electrodes and the spaces between the electrodes, as described in detail herein.

[0187] 44 is a perspective view of another exemplary variation of an expandable member 4450 comprising an electrode array. As shown therein, the electrode array may comprise a plurality of semi-elliptical electrodes 4460 and a plurality of leads 4470 that connect two or more of the electrodes to one another in a zigzag pattern. The electrode array may comprise a flex circuit.

[0188] 45A-45C are schematic diagrams of exemplary variations of electrode array configurations, such as a pair of twisted pair wires driven 90 degrees out of phase with alternating polarity. This configuration may enable the generation of a substantially uniform pulsed or modulated electric field. For example, electrode pair A (4510) and C (4530) may have opposite polarities, while electrode pair B (4540) and D (4520) may have opposite polarities. Other electrode array configuration types may be activated in alternative combinations to provide uniform treatment within the tissue (e.g., electrode pair A and B, electrode pair A and C, electrode pair A and D, electrode pair B and C, electrode pair B and D, electrode pair C and D). The distance between the electrode pairs will directly affect the magnitude of the electric field or the tissue treatment distance into the tissue. Electrode pairs may be selected by the controller to treat tissue at one or more predetermined tissue treatment depths.

[0189] Figure 45D is a plan view of an electric field intensity plot (4500) of an exemplary variation of the electrode array (4550). Figure 45E is a cross-sectional view of the electric field intensity plot (4502) of the electrode array (4550) shown in Figure 45D. The electrode array (4550) can be configured in a bipolar configuration to deliver non-thermal therapy primarily to duodenal tissue. For example, current flows from an anodal electrode, through tissue, to a cathodal electrode.

[0190] In some variations, the depth of electric field penetration into tissue may be based at least in part on the electrode spacing of the electrode array (e.g., 1.2 mm) and the voltage at the electrode array (e.g., 600 V). For example, the electrode array (4550) may be configured to generate a pulsed electric field that penetrates tissue to a depth of about 1 mm, while rapidly dissipating at the ends of the electrode array (4550) beyond a tissue depth of about 1.5 mm.

[0191] Figure 46A is a schematic perspective view of an exemplary variation of a coordinate system for an electrode array (4610) and a corresponding set of planes. Figure 46B shows electric field intensity plots corresponding to the electrode array (4610) at positions defined relative to the major planes shown in Figure 46A. The bottom two charts in Figure 46B show an equipotential plot at the target treatment depth (e.g., z=0.7 mm) and a histogram of the total electric field at the target treatment depth (e.g., z=0.7 mm).

[0192] Figure 47A is a schematic plan view of an exemplary variation in the polarity configuration of the electrode array (4700). Figure 47B shows an electric field intensity plot corresponding to the electrode array (4700) shown in Figure 47A at a location defined relative to the major plane shown in Figure 46A. The bottom two charts in Figure 47B show an equipotential plot at the target treatment depth (e.g., z = 0.7 mm, 1.4 mm) and a histogram of the total electric field at the target treatment depth (e.g., z = 0.7 mm, 1.4 mm). The electric field density corresponding to the electrode array (4700) shown in Figure 47B is denser than that corresponding to the electrode array (4600) shown in Figure 46B. The corresponding inactive electrode set can be at a floating potential while the other electrode set is active.

[0193] Figure 48 is a schematic plan view of an exemplary variation of the electrode array (4800) with exemplary dimensions and thermally bonded traces on the right side of the electrode array (4800). Figure 49 is a perspective view of a variation of the electrode array (4900) of a pulsed electric field device comprising multiple pairs of twisted pair wires. Figure 50 is a perspective view of another variation of the electrode array (5000) of a pulsed electric field device comprising multiple pairs of twisted pair wires. Twisted pair wires with exposed core locations can function similarly to a dot electrode configuration.

[0194] FIG. 85 is a perspective view of variations of an electrode (8530) of a pulsed electric field device (8500). The pulsed electric field device (8500) may include a first catheter (8510) (e.g., an inner shaft) and a second catheter (8520) (e.g., an outer shaft). In some variations, the second catheter (8520) can be slidably advanced over the first catheter (8510) and the electrode (8530) to hold the electrode (8530) in a compressed configuration. As shown in FIG. 85, the first catheter (8510) advanced distally relative to the second catheter (8520) can transition the electrode (8530) to an expanded configuration. In some variations, the electrode (8530) can be coupled (e.g., attached) to the first catheter (8510) at one end and coupled to the second catheter (8520) at the other end. The second catheter (8520) can be slidably advanced and / or retracted over the first catheter (8510). The electrode (8530) can transition between an expanded configuration and a compressed configuration.

[0195] The electrode (8510) may comprise an expandable metal mesh and may be configured to have a first polarity. Another electrode having a second polarity opposite to the first polarity may be disposed, for example, on the patient's skin (e.g., a grounding pad). In some variations, the size of the grounding pad may have a surface area sufficient to minimize current crowding and heat generation. In some variations, the pulsed electric field device (8500) may be configured in a monopolar or bipolar configuration. In some variations, the expandable electrode (8510) may be configured to contact tissue in the expanded configuration. In some variations, negative suction may be applied through the lumen of the electrode (8510) to enhance the tissue-electrode interface. In some variations, the pulsed electric field device (8500) may be flushed using a liquid (e.g., a conductive liquid, saline) while treating tissue as described herein. In some variations, the pulsed electric field device (8500) in the compressed configuration may be configured to be slidably advanced through a lumen (e.g., a working lumen) of a visualization device (e.g., an endoscope). For example, the pulsed electric field device (8500) in the compressed configuration can have a diameter of about 1.5 mm to about 4 mm.

[0196] Cleaning Generally, tissue treatment procedures using the pulsed electric field devices described herein may optionally include fluid delivery (e.g., fluid irrigation) during tissue treatment. In some variations, tissue treatment procedures may benefit from fluid irrigation, which may promote more reliable (e.g., consistent) electrical contact between the pulsed electric field device and the tissue, thus promoting a more uniform electric field and improved treatment results. Liquid irrigation of the tissue may further reduce tissue temperature through forced convection and reduce arcing. Additionally, fluid delivery may reduce corrosion of electrical insulation and the accumulation of electrolysis products. In some variations, the fluid may function as a salt bridge between the electrode and the tissue, allowing for control of resistivity. In variations in which a fluid is delivered, the fluid can be removed from the body cavity (e.g., aspirated from the body cavity) after application of the pulsed or modulated electric field. In some variations, the conductivity of the introduced or removed fluid may affect the delivered treatment. For example, adding a solution that is less conductive than the tissue may facilitate increasing the current introduced into the tissue. A conductivity similar to that of tissue may facilitate the transfer of electric field energy to tissue even in the absence of tissue contact between the electrode and the tissue. Finally, fluids with a higher conductivity than tissue can be removed.

[0197] In some variations, the pulsed electric field devices described herein can be configured to output fluid to irrigate tissue, such as duodenal tissue, of a patient. For example, an electrode array of a pulsed electric field device can engage the duodenum and be configured to output fluid (e.g., saline) where the electrodes contact the tissue. The electrode array, e.g., one or more electrodes of the electrode array, can output fluid between the electrode and the tissue, which can directly target the electrode and allow for a reduction in fluid volume. The electrode array can be energized to treat a predetermined portion of the tissue and resurface the duodenum. Utilizing an electrode array configured to deliver fluid can eliminate the need for a separate irrigation device and / or system. FIGS. 69A and 69B are plan and perspective views, respectively, of an exemplary variation of an electrode array (6900) comprising a substrate (6910) (e.g., a flex circuit) and a plurality of electrodes (6920). For example, the plurality of electrodes (6920) can comprise a plurality of substantially elongated electrodes disposed on the substrate (6910). In some variations, one or more (e.g., all, half, one-third, two-thirds) of the electrodes (6920) may include one or more (e.g., one, two, three, four, or more) fluid openings (6930) configured to output a fluid, such as saline solution, for irrigation. For example, the openings (6930) may be spaced along the length of the electrodes (6920). As shown in FIG. 69C, one or more openings (6930) may be disposed on the top of each electrode (6920), although openings (6930) may be disposed in any portion of the electrode (6920) (e.g., base, sidewall, edge). Additionally or alternatively, the substrate (6910) may include one or more fluid openings (not shown), such as between adjacent electrodes (6920). The electrode array (6900) may be in fluid communication with (e.g., fluidly coupled to) a fluid source (not shown) for fluid irrigation.

[0198] FIG. 69D is a perspective cross-sectional view of the electrode array (6900) showing the electrodes (6920) with fluid paths (6940). The fluid paths (6940) of the electrodes (6920) may be in fluid communication with the fluid openings (6930) of the electrodes (6920). One or more of the fluid paths (6940) may be in fluid communication with a fluid source such that fluid flows through the electrode array (6900). In some variations, the electrode array (6900) has a flow rate of about 0.001 cc / (s·cm 2 ) ~ approx. 1cc / (s cm 2 ) can output fluid at a predetermined rate. For example, the electrode array (6900) can be configured to drain water when in the expanded configuration. The fluid between the electrode array (6900) and the tissue can function in a manner similar to the tissue contact layer described herein.

[0199] In some variations, the expandable member may include one or more fluid pathways. In some variations, the fluid pathways may be configured to facilitate fluid flow for conduction (e.g., ionic fluids) and heat transfer (e.g., temperature control during treatment). In some variations, the fluid pathways may be configured to remove (e.g., via suction or negative pressure) fluids used for conduction, for example. The use of suction or negative pressure applied through the fluid pathways may draw tissue toward the expandable member (e.g., electrodes) and facilitate contact between the tissue and the electrode array (e.g., increase the contact area between the tissue surface and the electrode surface). In some variations, fluid openings may be disposed at the peaks of one or more of the multiple electrodes (6920). In some of these variations, fluid openings may be disposed between the electrodes, for example, at the lowest point (e.g., depression, valley) between a pair of electrodes (6920). In some variations, a fluid source may be in fluid communication with the electrode array (6900). In some variations, removal of fluid may facilitate apposition and / or contact of the tissue with the electrode array (6900).

[0200] Sensor In some variations, the pulsed electric field devices and systems described herein may include one or more sensors. Generally, the sensors can be configured to receive and / or transmit signals corresponding to one or more parameters. In some variations, the sensors may include one or more of a temperature sensor, an imaging sensor (e.g., a CCD), a pressure sensor, an electrical sensor (e.g., an impedance sensor, a voltage sensor, a magnetic sensor (e.g., an RF coil), an electromagnetic sensor (e.g., an infrared photodiode, an optical photodiode, an RF antenna), a force sensor (e.g., a strain gauge), a flow or velocity sensor (e.g., a hot wire anemometer, a vortex flowmeter), an acceleration sensor (e.g., an accelerometer), a chemical sensor (e.g., a pH sensor, a protein sensor, a glucose sensor), an oxygen sensor (e.g., a pulse oximetry sensor), an audio sensor, a sensor for sensing other physiological parameters, combinations thereof, and the like. In some variations, the electrical characteristics of the cell may also be determined by applying an alternating current signal at a particular frequency to measure the voltage.

[0201] Temperature measurements performed during a tissue treatment procedure can be used to determine one or more of tissue contact (e.g., full contact, partial contact, no contact) with the pulsed electric field device and successful energy delivery to the tissue. Thus, the safety of the tissue treatment procedures described herein can be enhanced through temperature measurement and monitoring. In some variations, tissue temperature monitoring can be used to prevent excessive energy delivery to the tissue, which could otherwise result in insufficient or suboptimal treatment results. For example, if tissue temperature measurements exceed a predetermined threshold, energy delivery can be inhibited or delayed.

[0202] As described herein, pulsed or modulated electric field treatment of tissue inevitably heats the tissue around the electrodes locally. Temperature feedback allows for variations in electrical conductivity and contact resistance to be taken into account so as not to overheat the tissue to the point of necrotic cell death (e.g., heat-induced ablation). In some variations, a four-point probe can be configured as an invasive sensor element within the electrode array. In a four-point probe connection, a differential voltage generated through the sense lines can be sensed by a first pair of conductors, and a current drive that generates the differential voltage can be applied by a second pair of conductors. In some variations, the drive current or drive voltage can be pulsed. For example, FIG. 51A is a schematic circuit diagram of an exemplary variation of an expandable member (5100) and a tissue temperature sensor array (5120). The electrode array (5110) can include multiple elongated electrodes parallel to and spaced apart from one another. The electrode array (5110) can further include a tissue temperature sensor array as described herein. For example, in some variations, one or more tissue temperature sensors can be disposed between adjacent electrodes in the array (5110). For example, the tissue temperature sensors can be configured to extend parallel or interdigitated between adjacent elongated electrodes (5110). FIG. 51A illustrates multiple groups of electrodes (e.g., zones A, B, and C) with corresponding temperature sensors. The tissue temperature sensor array can include a common point (5120) where a four-point drive current (e.g., sense current) begins to pass through a temperature sense trace (5140). Multiple temperature sensors can be provided per zone. For example, trace (5140) is between the sense points of zones A and B, and trace (5140) is in series with trace (5130). The voltage difference between the sense current in each zone divided by the sense current flowing through the entire trace can provide the resistance of trace (5140). The measured change in resistance of trace (5140) can correspond to a change in temperature, given the known change in resistance of copper with temperature.

[0203] The temperature sensors can be configured to be thermally coupled and in contact with the tissue so that the measured sensor temperature corresponds to the tissue temperature. The temperature sensors can be electrically isolated from the tissue so that the sense current passes only through the temperature sensors and high voltage driving of the electrodes does not damage the temperature sensors. In some variations, the electrode array can include one or more drive circuits for applying voltage or current pulses to the temperature sensors and sense circuits for measuring the voltage or current across the temperature sensors.

[0204] In some variations, the temperature sensor (5120) may comprise an insulator configured to maintain a pulse waveform configured to generate a pulsed or modulated electric field for treating tissue without breakdown. In some variations, the insulator may comprise a thickness of at least about 0.02 mm. In some variations, the temperature sensor (5120) may comprise a width of up to about 0.07 mm and a length of at least about 2 cm. In some variations, the distance between the temperature sensor (5120) and the electrode (5110) may be at least about 0.2 mm. In some variations, the temperature sensor (5120) may extend substantially parallel to the elongated electrode (5110).

[0205] In some variations, each of the temperature sensors may have a temperature resolution of less than about 0.5° C. For example, a half-ounce copper electrode about 0.075 mm wide and about 2 cm long may have a resistance of about 0.267 ohms at 37° C. and about 0.273 ohms at 43° C., and may provide a resolution of about 0.5° C. for every 2 cm of electrode. Longer electrodes may provide proportionally better sensitivity. In some variations, the temperature sensors may have a thermal diffusion time constant of less than about 5 milliseconds.

[0206] In some variations, the measured temperature can be used to determine whether the electrode array is in contact with tissue. For example, a current pulse of length τ can be applied to the material surrounding the sense wires to approximately

number

number

number

[0207] I s =0.5A and L s = 2cm and R s Using ΔT = 0.276 ohms results in ΔT = 1.6°C. This constant temperature difference is present in all measurements and is therefore removed from the temperature rise measurements. The temperature rise when there is no tissue contact is given by equation (6).

number

[0208] Z f is the thickness of the substrate. Z f = 0.135 mm and τ = 1 ms, resulting in ΔT = 0.65°C. Pulses longer than about 6 ms can cause an increase in the measured temperature corresponding to the tissue temperature due to heating of the wire. The maximum pulse width is given by equation (7). τ=s 2 / κ Equation (7)

[0209] s is the spacing between the temperature sensors. For temperature sensors spaced approximately 0.075 mm apart, the maximum pulse duration may be approximately 21 milliseconds before the wire begins to heat linearly with time. By monitoring the rate of temperature rise, tissue contact can be determined. If the measured temperature exceeds a predetermined threshold, energy delivery may be modified (e.g., reduced, inhibited).

[0210] In some variations, the temperature sensor can be configured to operate in a second mode where one conductor in the temperature sensor carries current and voltage across a fine trace. In the second mode, the temperature can be calculated using V / I=R across the trace, assuming the temperature sensor has a rapidly changing resistance.

[0211] FIG. 51B is a schematic circuit diagram of an exemplary variation of an electrode array (5110) including multiple temperature sensors (5120) and a reference generator (5160) (described in more detail with respect to FIGS. 52 and 59). FIG. 51C is an image of a visual marker on duodenal tissue produced by the expandable member (5100) shown in FIG. 51B. The expandable member (5100) may define multiple openings (5170) (e.g., fluid openings, through-holes) configured for one or more of suction and / or fluid irrigation, as described in detail herein. Additionally, the expandable member (5100) may include one or more tracks (5180) configured to couple to one or more of gears and friction rollers. The track (5180) may include multiple spaced openings in the expandable member (5100) configured to assist in expansion and contraction of the expandable member between a compressed configuration and an expanded configuration. In some variations, the fiducial generator (5160) may comprise a length of approximately 2 mm and a width of approximately 2 mm. In some variations, one or more of the fiducial generators (5160) may comprise a shape having one or more vertices (e.g., corners, corner points, intersections), such as a square, rectangle, triangle, polygon, etc. Visualization markers formed on tissue may be easier to identify and visualize if they are formed with sharp corners rather than rounded edges. For example, a visual marker having a circular shape may be relatively difficult to distinguish from natural tissue.

[0212] In some variations, one or more of the reference generators (5160) may comprise a DC resistive heater configured to mark the tissue. The reference generators (5160) may be electrically isolated from the electrode array (5110). In some variations, one or more of the reference generators (5160) may be configured to raise the temperature of the top layer of mucosal tissue (e.g., less than 0.1 mm deep) to an average of about 49°C in less than about 2.5 seconds. In this manner, one or more of the visual markers may fade and become visually invisible after about one day. In some variations, histological evidence of the visual markers may disappear after about three days. The visual markers may be configured to identify the treatment site and aid in repositioning the ablation device. For example, an operator may advance the expandable member (5100) past the most distal visual marker in the duodenum during the ablation procedure.

[0213] The duodenal tissue (5102) shown in FIG. 51C includes a pair of visual markers (5162) generated on the tissue (5102) by a fiducial generator (5160). In some variations, the visual markers can be identified based on one or more of the color, shape, number, and size of the markers left on the tissue. The visual markers can be visualized, for example, by using an endoscope. A set of repeating shapes may be easier to distinguish than a single visual marker. FIG. 51B shows a set of eight fiducial generators (5160).

[0214] FIG. 51D is a detailed schematic circuit diagram of the expandable member 5100, showing the temperature sensors 5120 and openings 5170 without the electrode array 5110 for clarity. As shown in FIG. 51D, the temperature sensors 5120 may comprise a serpentine shape that may meander back and forth along a predetermined path. For example, the temperature sensors 5120 may curve around each opening 5170 in the expandable member 5100. As described herein, one or more openings 5170 may extend through the expandable member 5100 such that tissue that may come into contact with the expandable member 5100 can be drawn into and through the openings 5170. In some variations, the reference generator 5160 may be spaced apart between adjacent electrode array 5110 sections (e.g., between section 1 and section 2).

[0215] In some variations, the electrode array (5110) may have a length of approximately 60 mm and a width of approximately 20 mm. Thus, approximately 20 mm of the duodenum can be treated at one time. In some variations, the electrode array (5110) may be divided into two or more independently powered sections to reduce signal generator requirements. For example, the electrode array (5110) may have a circumferential length of approximately 60 mm. In an electrode array (5110) with two sections, each section may have a circumferential length of approximately 27 mm. In some variations, the configuration and arrangement of the electrode array (5110) on the expandable member may facilitate one or more of manufacturing techniques and tissue temperature measurement at a predetermined depth. In some variations, a set of reference generators may be disposed between sections of the electrode array; for example, each reference generator may generate a visual marker having a length and width of approximately 2 mm. The expandable member (5100) illustrated in FIG. 51B and described herein may correspond to the expandable member (7600) illustrated in FIG.

[0216] In some variations, one or more of the temperature sensors (5120) (e.g., temperature traces) can generally extend across the multiple electrodes of the electrode array (5110). For example, one or more of the temperature sensors (5120) can comprise a generally serpentine shape, which can be continuous. In some variations, the temperature sensor (5120) can measure an average temperature across a predetermined portion of the sensor (5120), which can be a better representation of the tissue temperature. In contrast, temperature measurements taken very close to the ends of the electrodes can result in misleadingly high temperatures that are not representative of the temperature throughout the tissue. In some variations, the temperature trace lines can be disposed on the electrode side of the expandable member (5100) and / or along the opposite side of the expandable member (5100). In some variations, temperature measurements from one or more temperature sensors (5120) can correspond to the temperature of the tissue at a predetermined depth.

[0217] In some variations, one or more of the temperature sensors (5120) may have a thickness of about 0.030 mm to about 0.040 mm and a width of about 0.09 mm to about 0.12 mm. In some variations, a temperature sensor may be spaced apart from itself and / or other temperature sensors by about 0.10 mm to about 0.17 mm. In some variations, one or more temperature sensors (5120) may be disposed on the expandable member (5100) using button plating.

[0218] In some variations, visually marking treated tissue can assist an operator in performing tissue treatment procedures in which separate portions of tissue are treated sequentially. In some variations, the reference generator can be configured to generate a visual marker on the tissue, allowing the treated portion of the tissue to be visualized within a body cavity (e.g., the duodenum). In some of these variations, the reference generator can be disposed on the substrate of the electrode array along the periphery of the elongated electrode. In some variations, the reference generator can include one or more temperature sensors as described herein. In some variations, the reference generator can include a spiral or serpentine shape. In some variations, the high-current pulse can be configured to heat one or more reference generators to 80°C or higher, thereby creating a visually discernible mark on the tissue in contact with the reference generator. Figure 52A is a schematic circuit diagram (5200) of an exemplary variation of an electrode array (5210) and multiple (e.g., four) reference generators (5220). Figure 52B is a detailed view of the schematic circuit diagram of the electrode array (5210) and one spiral reference generator (5220). Figure 59 is an image of an exemplary variation of an electrode array (5900) comprising multiple electrodes grouped into different sections (5910, 5920, 5930, 5940), a connector pad (5950), and multiple reference generators (5960). For example, the electrode array (5900) can be grouped into a first section (5910), a second section (5920), a third section (5930), and a fourth section (5940). Each of the sections can be wired to a corresponding pad (S1, S2, S3, S4) of the connector pad (5950). In some variations, each section (5910, 5920, 5930, 5940) may include at least one reference generator (5960). The reference generators (5960) may be wired in series. In some variations, the electrode array (5210) within the tissue may be deployed at different diameters based on the local diameter of the tissue being treated (e.g., the duodenum).The electrode array (5210) can be configured such that only sections of the electrode array (5900) that are in at least partial contact with tissue can be energized by the signal generator. In some variations, the signal generator can be configured to sequentially drive each section of the electrode array (5900).

[0219] In some variations, one or more reference generators can be disposed between electrodes of the electrode array, for example, the reference generators can have elongated shapes between adjacent electrodes and be disposed near the edges of the electrode array, which can reduce the length of one or more of the elongated electrodes.

[0220] expander Generally, the dilators described herein can be configured to aid in the advancement of one or more portions of a pulsed electric field device into and through a body cavity or lumen, such as the duodenum. In some variations, the dilator can be generally configured to dilate a body cavity or lumen, such as the lumen of the duodenum. The dilator can be atraumatic in shape to minimize inadvertent or unintended injury and can comprise any shape (e.g., conical) suitable for enlarging a tissue lumen. For example, in some variations, the dilator can comprise a cone shape with a taper of about 1 degree to about 45 degrees, which can facilitate the advancement of the PEF device through the gastrointestinal tract. In some variations, the dilator can comprise PET, PEBA, PEEK, PTFE, silicone, PS, PEI, latex, sulfate, barium sulfate, copolymers, combinations thereof, or the like. In some variations, the dilator can comprise a solid construction. In some variations, the dilator can comprise multiple materials configured to provide desired stiffness and compliance along the length of the dilator. In some variations, the dilator may include one or more components configured to facilitate advancement of the guidewire.

[0221] In some variations, the dilator may have a length of about 2 mm to about 10 cm. In some variations, the dilator may have a taper of about 5 degrees to about 30 degrees relative to the longitudinal axis of the dilator. In some variations, the distal end of the dilator may be atraumatic (e.g., rounded, blunt). In some variations, the pulsed electric field device may include multiple dilators (e.g., 2, 3, 4, 5, 6, or more). For example, each dilator may be disposed proximally and distally of the expandable member. This allows for smooth advancement of the pulsed electric field device proximally and distally.

[0222] In some variations, the dilator may include a recess configured to facilitate mating or coupling with another elongate member, such as a visualization device (e.g., an endoscope). For example, this may allow the dilator and expandable member to be removably coupled to the visualization device during a treatment procedure. The lengths and tapers of the multiple dilators of the pulsed electric field device may be the same or different. For example, the distal dilator may have a steeper taper than the proximal dilator.

[0223] Long, slender body Generally, the elongate bodies (e.g., catheters) described herein can be configured to deliver an electrode array to the duodenum to treat tissue, such as duodenal tissue. In some variations, the elongate body can include a shaft constructed from a flexible polymeric material such as Teflon, nylon, Pebax, urethane, combinations thereof, or the like. In some variations, the pulsed electric field device can include one or more steerable or deflectable catheters (e.g., one-way, two-way, four-way, omnidirectional). In some variations, the elongate body can include one or more pull wires configured to steer or deflect a portion of the elongate body. In some variations, the elongate body can have a length of about 5 cm to about 23 cm and / or a bend radius of about 45 degrees to about 270 degrees. In some variations, the elongate bodies described herein can include a lumen through which another elongate body and / or a guidewire can slide. In some variations, the elongate body can include multiple lumens. For example, the elongate body may include one or more of an inflation lumen, a fluid lumen, a guidewire lumen, and a lead lumen.

[0224] In some variations, the elongate body may be woven, braided, and / or coiled and may be constructed from materials (e.g., nylon, stainless steel, nitinol, polymers) configured to enhance pushability, twistability, and flexibility. In some variations, one or more of the first and second elongate bodies may include a metal-based radiopaque marker comprising one or more of rings, bands, and inks (e.g., platinum, platinum-iridium, gold, nitinol, palladium) configured to enable fluoroscopic visualization. In some variations, one or more of the first and second elongate bodies may include a magnetic member configured to attract and bond the bodies to each other. In this manner, the first elongate body need not include a lumen for the second elongate body. In some variations, the elongate body may include from about 2 to about 15 layers of material to achieve a predetermined set of properties.

[0225] handle Generally, the handles described herein can be configured to allow an operator to grasp and control one or more of the position, orientation, and operation of the pulsed electric field device. In some variations, the handle can include actuators that allow translation and / or rotation of the first and second elongate bodies in addition to steering with an optional delivery catheter. In some variations, control of the expandable member can be performed by an expansion member of the handle (e.g., a screw / rotation actuator, an inflation actuator). In some variations, the handle can be configured to control PEF energy delivery to the electrode array of the expandable member using, for example, a handheld switch and / or a foot switch.

[0226] FIG. 84 is a cross-sectional perspective view of a set of lead wires (8400) (e.g., power transmission wires, wiring harness). In some variations, the set of lead wires (8400) can couple a signal generator and / or handle to one or more distal components (e.g., electrodes, reference generator, temperature sensor) of a pulsed electric field device (not shown for clarity). The lead wires (8400) can be configured for one or more of power delivery, temperature sensing, and reference generation. In some variations, the power transmission wires (8430) can comprise multiple twisted pair wires. In some variations, the set of twisted pair wires (8430) can comprise from about 1 to about 20 twisted pairs, based on the frequency and current of the energy being delivered. In some variations, the set of twisted pair lead wires (8430) can facilitate high amperage and frequency transmission while minimizing losses. The set of twisted pair wires (8430) can be the same diameter or different diameters. For example, the wire size and insulation thickness can be configured to minimize one or more of inter-wire inductance, wire resistance, wire temperature rise, and wire skin effect. Additionally or alternatively, specially woven Litz wire and / or tubular conductors (e.g., coaxial cable) can be used to minimize these variations (e.g., inductance, resistance, temperature, skin effect) and mitigate losses. In some variations, the reference generating wire (8410) can be configured to deliver energy to one or more reference generators as described herein. In some variations, the reference generating wire (8410) may be untwisted. In some variations, the temperature sense wire (8420) can be configured to measure temperature from one or more temperature sensors of the pulsed electric field device. In some variations, the reference generating wire (8410) can be untwisted and have a larger diameter than the power transmission wire (8430) and the reference generating wire (8410).

[0227] insulator Generally, the insulators described herein can be configured to electrically insulate another portion of the electrode array, the expandable member, the inflatable member, the dilator, and / or the elongate body of the pulsed electric field device from one another. In some variations, the insulator may comprise one or more of poly(p-xylylene) polymers (e.g., Parylene C, Parylene N), polyurethane (PU), polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), polyimide (PI), polyester, polyethylene terephthalate (PET), PEEK, polyolefin, silicone, copolymers, ceramic, combinations thereof, and the like.

[0228] Guidewire In some variations, a guidewire can be slidably disposed within the lumen of the elongate body of the pulsed electric field device. The guidewire can be configured to aid in the advancement of the pulsed electric field device through the gastrointestinal tract. In some variations, the first and second elongate bodies of the pulsed electric field device can translate along the guidewire, relative to each other, and / or relative to the duodenum. In some variations, the guidewire can comprise one or more of stainless steel, nitinol, platinum, and other suitable biocompatible materials. In some variations, the guidewire can have variable stiffness along its length. For example, the distal tip can be configured to be malleable (e.g., floppy), and the elongate body of the guidewire can be relatively stiff to aid in pushability through the patient's anatomy. In some variations, the guidewire can have a diameter of about 0.014 inches to about 0.060 inches and a length of about 180 cm to about 360 cm.

[0229] signal generator Generally, the signal generators described herein can be configured to provide energy (e.g., a PEF energy waveform) to a pulsed electric field device to treat a predetermined portion of tissue, such as duodenal tissue. In some variations, the PEF systems described herein can include a signal generator having an energy source and a processor configured to deliver a waveform for delivering energy to the tissue. The waveforms disclosed herein can assist in the treatment of diabetes. In some variations, the signal generator can be configured to control the generation and delivery of the waveform in response to received sensor data. For example, if a temperature sensor measurement identifies that the tissue temperature exceeds a predetermined threshold or range (e.g., exceeds a predetermined maximum temperature), energy delivery can be inhibited.

[0230] The signal generator can generate and deliver several types of signals, including, but not limited to, AC current, square-wave AC current, sinusoidal AC current, AC current interrupted at predetermined time intervals, multiple profile current pulse trains of various power intensities, current (DC) impulses, stimulation range impulses, and / or hybrid electrical impulses. For example, the signal generator can generate monophasic (DC) pulses and biphasic (DC and AC) pulses. In some variations, the signal generator can be configured to generate a current of about 1 A to about 200 A delivered to a system resistance of about 1 V to about 3,000 V and about 2 Ω to about 30 Ω at a frequency of about 50 kHz to about 950 kHz. The signal generator may include a processor, memory, an energy source (e.g., a current source), and a user interface. The processor can incorporate data received from one or more of the memory, the energy source, the user interface, and the pulsed electric field device. The memory may further store instructions that cause the processor to execute modules, processes, and / or functions associated with the system, such as generating and delivering waveforms. For example, the memory may be configured to store patient data, clinical data, treatment data, safety data, etc.

[0231] Generally, to induce an electric field across a cell membrane of greater than about 0.5 V in the duodenum, a voltage of about 1,000 V / cm to about 2,500 V / cm or more is required at the treatment depth of the tissue. In some variations, to induce an electric field across a cell membrane of greater than about 0.5 V in the duodenum, a voltage of about 1,500 V / cm to about 4,500 V / cm or more is required at the treatment depth of the tissue, including all ranges and subvalues ​​therebetween. Even with relatively low tissue conductivity (e.g., about 0.3 S / m), a bulk tissue heating rate of at least about 800°C / sec can be produced. The maximum temperature rise to be generated is about 8°C, and as a result, the maximum continuous on-time (100% duty cycle of alternating polarity pulses) can be about 10 milliseconds. For example, a pulse waveform can comprise pairs of about 1 μs unipolar pulses in about 5 to about 500 groups, with a delay between each group. In some variations, series of these groups can be applied repeatedly, with increasingly longer delays between series. In some variations, a series of sequences may be applied with a longer delay between sequences, hi some variations, a cumulative on-time of about 15 milliseconds may be distributed over about 10 seconds.

[0232] In some variations, the signal generator can be configured to generate current, voltage, and power in a pulsed or modulated electric field spectrum of about 250 kHz to about 950 mMHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A per square centimeter of tissue. In some variations, the signal generator can be configured to drive a tissue resistance load of about 5 ohms to about 30 ohms. For example, the current density can be about 0.6 A to about 100 A per square centimeter of tissue from the electrode array. In some variations, the pulse waveform can include about 1 to about 50 pulse groups, with about 1 to about 100 pulses per group. In some of these variations, the pulse waveform can include a group delay of about 10 μs to about 4000 μs and an escaping rate of about 50 milliseconds to about 4000 milliseconds. For example, a balanced bipolar pulse waveform (e.g., within 10%) can reduce sympathetic excitation, thereby reducing perceived pain and voluntary muscle contractions. Microsecond pulses of approximately 1 μs to approximately 10 μs can induce cell lysis while minimizing nerve stimulation. The electric field distribution produced by short bipolar pulses is less dependent on tissue homogeneity, especially in anisotropic regions.

[0233] In some variations, the set of bipolar pulses can be divided into bursts of bipolar pairs with a time delay between bursts. This allows the heat generated at the cell membrane to dissipate, allowing for more treatment before cell lysis transitions to necrosis. The total time the pulsed or modulated electric field is applied to the tissue determines the density and size of the membrane pores and the extent to which ionic flow has altered the cell contents. For example, if the thermal diffusivity κ of the tissue is 0.13 mm, 2 / s, the cell diameter D cell If the temperature is 10 microns, the thermal diffusion time is approximately

number

[0234] Figure 53 is a circuit block of a signal generator (5300) including a power supply (5310), a high-voltage DC power supply (5320), an output amplifier (5330), a controller (5340), a user interface (5350), and a display (5360). The controller (5340) may include a processor. Generally, a processor (e.g., a CPU) described herein can process data and / or other signals to control one or more components of the system. The processor can be configured to receive, process, compile, calculate, store, access, read, write, and / or transmit data and / or other signals. In some variations, the processor can be configured to access or receive data and / or other signals from one or more of a sensor (e.g., a temperature sensor) and a storage medium (e.g., a memory, a flash drive, a memory card). In some variations, the processor may be any suitable processing device configured to operate and / or execute a set of instructions or code, and may comprise one or more data processors, image processors, graphics processing units (GPUs), physical processing units, digital signal processors (DSPs), analog signal processors, mixed-signal processors, machine learning processors, deep learning processors, finite state machines (FSMs), compression processors (e.g., data compression to reduce data rates and / or memory requirements), encryption processors (e.g., for secure wireless data and / or power transfer), and / or central processing units (CPUs). The processor may be, for example, a general-purpose processor, a field-programmable gate array (FPGA), an application-specific integrated circuit (ASIC), etc. The processor may be configured to operate and / or execute application processes and / or other modules, processes and / or functions associated with the system.The underlying device technology may be provided in a variety of component types (e.g., metal-oxide semiconductor field effect transistor (MOSFET) technologies such as complementary metal-oxide semiconductor (CMOS), bipolar technologies such as emitter-coupled logic (ECL), polymer technologies (e.g., silicon-conjugated polymers and metal-conjugated polymer-metal structures), mixed analog and digital technologies, etc.).

[0235] The systems, devices, and / or methods described herein can be implemented by software (executed on hardware), hardware, or a combination thereof. Hardware modules may include, for example, general-purpose processors (or microprocessors or microcontrollers), field-programmable gate arrays (FPGAs), and / or application-specific integrated circuits (ASICs). Software modules (executed on hardware) may be expressed in various software languages ​​(e.g., computer code), including C, C++, Java, Python, Ruby, Visual Basic, and / or other object-oriented, procedural, or other programming languages ​​or development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, machine instructions such as those generated by a compiler, code used to create web services, and files containing high-level instructions executed by a computer using an interpreter. Additional examples of computer code include, but are not limited to, control signals, encryption code, and compression code.

[0236] In general, the pulsed electric field devices described herein may include memory configured to store data and / or information. In some variations, the memory may include one or more of random access memory (RAM), static RAM (SRAM), dynamic RAM (DRAM), memory buffer, erasable programmable read-only memory (EPROM), electrically erasable read-only memory (EEPROM), read-only memory (ROM), flash memory, volatile memory, non-volatile memory, combinations thereof, etc. In some variations, the memory may store instructions that cause a processor to perform modules, processes, and / or functions associated with the pulsed electric field device, such as signal waveform generation, pulsed electric field device control, data and / or signal transmission, data and / or signal reception, and / or communications. Some variations described herein relate to computer storage products with non-transitory computer-readable media (which may also be referred to as non-transitory processor-readable media) having instructions or computer code for performing various computer-implemented operations. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not include a transitory, propagating signal itself (e.g., a propagating electromagnetic wave that carries information over a transmission medium such as space or a cable). The medium and computer code (also called code or algorithms) may be designed and constructed for a specific purpose or for a variety of purposes.

[0237] In some variations, the pulsed electric field device may further include a communications device configured to allow an operator to control one or more of the devices of the PEF system. The communications device may include a network interface configured to connect the pulsed electric field device to another system (e.g., the Internet, a remote server, a database) via a wired or wireless connection. In some variations, the pulsed electric field device may communicate with other devices (e.g., a mobile phone, a tablet, a computer, a smartwatch, etc.) via one or more wired and / or wireless networks. In some variations, the network interface may include one or more of a radio frequency receiver / transmitter, an optical (e.g., infrared) receiver / transmitter, etc. configured to communicate with one or more devices and / or networks. The network interface may communicate with one or more of the pulsed electric field device, the network, the database, and the server via a wired and / or wireless connection.

[0238] The network interface may include RF circuitry configured to receive and / or transmit RF signals. The RF circuitry converts electrical signals to / from electromagnetic signals and can communicate with communication networks and other communication devices via electromagnetic signals. The RF circuitry may include known circuits for performing these functions, including, but not limited to, an antenna system, an RF transceiver, one or more amplifiers, a tuner, one or more oscillators, a mixer, a digital signal processor, a CODEC chipset, a subscriber identity module (SIM) card, memory, etc.

[0239] Wireless communication through any of the devices may use any of a number of communication standards, protocols, and technologies, including Global System for Mobile Communications (GSM), Enhanced Data GSM Environment (EDGE), High Speed ​​Downlink Packet Access (HSDPA), High Speed ​​Uplink Packet Access (HSUPA), Evolution, Data Only (EV-DO), HSPA, HSPA+, Dual Cell HSPA (DC-HSPA), Long Term Evolution (LTE), Near Field Communication (NFC), Wideband Code Division Multiple Access (W-CDMA), Code Division Multiple Access (CDMA), Time Division Multiple Access (TDMA), Bluetooth, Wireless Fidelity (WiFi) (e.g., IEEE 802.11b / g), and the like. 2.11a, IEEE 802.11b, IEEE 802.11g, IEEE 802.11n, etc.), Voice over Internet Protocol (VoIP), Wi-MAX, protocols for email (e.g., Internet Message Access Protocol (IMAP) and / or Post Office Protocol (POP)), instant messaging (e.g., Extensible Messaging and Presence Protocol (XMPP), Session Initiation Protocol for Instant Messaging and Presence Leverage Extension (SIMPLE), Instant Messaging and Presence Service (IMPS)), and / or Short Message Service (SMS), or any other suitable communication protocol. In some variations, devices herein may communicate directly with each other without transmitting data over a network (e.g., via NFC, Bluetooth, WiFi, RFID, etc.).

[0240] In some variations, the user interface may include an input device (e.g., a touchscreen) and an output device (e.g., a display device) and may be configured to receive input data from one or more of a pulsed electric field device, a network, a database, and a server. For example, operator control of the input device (e.g., a keyboard, a button, a touchscreen) may be received by the user interface and then processed by a processor and memory for the user interface to output a control signal to the pulsed electric field device. Some variations of the input device may include at least one switch configured to generate a control signal. For example, the input device may include a touch surface for an operator to provide an input (e.g., a finger touch on the touch surface) corresponding to the control signal. Input devices with touch surfaces may be configured to detect contact and movement on the touch surface using any of a number of touch sensitivity technologies, including capacitive, resistive, infrared, optical imaging, dispersive signal, acoustic pulse recognition, and surface acoustic wave technologies. In variations of input devices that include at least one switch, the switch may comprise, for example, at least one of a button (e.g., hard key, soft key), a touch surface, a keyboard, an analog stick (e.g., a joystick), a directional pad, a mouse, a trackball, a jog dial, a step switch, a rocker switch, a pointer device (e.g., a stylus), a motion sensor, an image sensor, and a microphone. The motion sensor can receive operator movement data from the optical sensor and classify the operator's gestures as control signals. The microphone can receive audio data and recognize the operator's voice as a control signal.

[0241] A haptic device can be incorporated into one or more of the input and output devices to provide additional sensory output (e.g., force feedback) to the operator. For example, the haptic device may generate a haptic response (e.g., vibration) to confirm an operator input to the input device (e.g., touch surface). As another example, the haptic feedback may indicate that an operator input is overridden by a pulsed electric field device.

[0242] II. Method Also described herein are methods for treating tissue. In some variations, the methods may include treating diabetes in a patient using the systems and devices described herein. In particular, the systems, devices, and methods described herein can use pulsed or modulated (e.g., sinusoidal) electric fields to resurface a predetermined portion of tissue, e.g., duodenal tissue, for, e.g., treating diabetes. In some variations, the generated pulsed or modulated electric field can be substantially uniform such that pulsed or modulated electric field energy for tissue treatment can be delivered to a predetermined portion of the duodenum (e.g., the mucosal layer) without significant energy delivery to deeper layers of the duodenum. Thus, these methods can improve the efficiency and effectiveness of energy delivery to duodenal tissue. Furthermore, the methods described herein can avoid excessive thermal tissue heating that is inevitably generated by the application of one or more other thermal energy modalities to tissue.

[0243] In some variations, the method may include using a pulsed electric field system with a closed-loop temperature feedback system. The temperature feedback system may include a temperature sensor configured to monitor tissue temperature. In these variations, the method may inhibit delivery of a pulse waveform by the signal generator based on the sensor measurement. In some variations, the temperature rise of the tissue may be limited to about 3°C ​​to about 10°C, about 2°C to about 5°C, or about 3°C ​​to about 8°C, including all subvalues ​​and ranges therebetween. In some of these variations, the reference generator may be configured to thermally generate visual markers (e.g., fiducials) on the tissue. The visual markers may assist in identifying the tissue treatment area during and after treatment.

[0244] How to Treat Diabetes Generally, methods for treating diabetes can involve generating pulsed or modulated electric fields to induce changes in (e.g., treat) duodenal tissue. Normally, the small intestine sends signals to the brain, pancreas, and liver to promote glycemic hemostasis. For example, enteroendocrine cells in the mucosal villi can generate these signals. Duodenal mucosal resurfacing using the systems, methods, and devices described herein can be used, for example, to treat type 2 diabetes. Clinical studies have shown that duodenal mucosal resurfacing of the duodenal mucosal layer is a safe procedure that can positively impact glycemic hemostasis in patients with type 2 diabetes.

[0245] In some variations, the pulsed or modulated electric field can cause cell lysis in the tissue that is at least 50% pore-induced and less than 50% heat-induced. In some variations, a method of treating diabetes can include advancing a pulsed electric field device toward a patient's duodenum. In some of these variations, the patient can be positioned in a left lateral decubitus position during the procedure, and the duodenum can optionally be insufflated (e.g., using CO2 or saline). The pulsed electric field device can include an elongate body and an expandable member comprising an electrode array. Upon entering the duodenum, the expandable member can transition to an expanded configuration. In some variations, one or more turns of the expandable member can be deployed to contact the duodenum. In some variations, a visualization device (e.g., an endoscope) can be advanced into the duodenum to visualize, inspect, and / or confirm the treatment area during the procedure. For example, one or more transparent portions of the pulsed electric field device can enable the visualization device to identify the ampulla of the duodenum. Once the device is positioned at a desired location within the duodenum, a pulse waveform can be delivered to the electrodes to generate a pulsed electric field to treat a portion of the duodenum. It should be understood that any of the systems and devices described herein can be used in the methods described herein.

[0246] In some variations, the method for treating diabetes may include one or more of applying a radially outward force to the tissue to stretch (e.g., expand) the tissue and applying a negative pressure (e.g., suction) to the tissue to facilitate a consistent tissue-electrode interface. For example, tissue stretched or expanded by the expandable member of a pulsed electric field device in the expanded configuration, whether by application of a radial force and / or negative pressure, may have a more uniform tissue thickness, which may aid in consistent energy delivery and treatment. In some variations, the tissue may contact the expandable member in the expanded configuration within the duodenum. A visualization device (e.g., an endoscope) may be advanced into and disposed within the lumen of the expandable member in the expanded configuration. The visualization device may then be configured to generate sufficient negative pressure to draw the tissue into and / or through one or more openings (e.g., fluid openings) in the expandable member. This may reduce tissue tenting and / or air pockets on the electrode and ensure a consistent tissue-electrode interface around the duodenum. Additionally, suction can allow for a reduction in the radial force applied by the expandable member. In some variations, the negative pressure (e.g., suction) applied to the tissue can be about 50 mmHg to about 75 mmHg. In some variations, the negative pressure (e.g., suction) applied to the tissue can be about 100 mmHg to about 250 mmHg, applied intermittently or for relatively short periods of time. For example, higher negative pressures can be applied in bursts or quickly to ensure contact between the tissue and the electrode without tissue pressure necrosis.

[0247] Figure 71B is a cross-sectional image of an undistracted duodenum (7100), which has a varying thickness around its circumference. As shown therein, in a natural state (e.g., no external force is applied, undistracted), duodenal tissue has a variable thickness around the circumference of the duodenum. Figure 71A is a cross-sectional image of a pulsed electric field device (7110) in an expanded configuration within the duodenum (7100). The pulsed electric field device (7110) comprises an expandable member (7120), an electrode array (7122), a dilator (7130), and an elongate body (7140). The expanding pulsed electric field device (7110) expands to apply a radial force to the duodenal tissue, expanding the duodenum (7110), reducing the thickness of the duodenal tissue, and / or creating a more uniform thickness of the duodenal tissue around the circumference of the duodenum compared to an unexpanded duodenum. The stretched or expanded tissue may have a narrower range of tissue thickness than unexpanded tissue. In some variations, approximately 1 inch to approximately 15 inches of water (inH2O) can be applied to expand but not damage the tissue through pressure necrosis. For example, the expandable member can be configured to generate approximately 2 inches to approximately 6 inches of water (inH2O) to slightly expand tissue, such as duodenal tissue. Expanded tissue stretched by the expandable member in the expanded configuration can reduce the thickness of the tissue wall, thereby allowing for a lower dose of energy to treat a given depth of tissue. The stretched tissue may have a realigned (e.g., reoriented) cellular structure that increases the circumference of the tissue. Reducing the total energy delivery may correspond to a lower overall temperature rise in the tissue, which may promote a faster and safer healing cascade as well as improve the safety profile of the treatment procedure.

[0248] In some variations, negative pressure can be applied to the tissue to ensure uniform contact between the tissue and the electrode array during treatment. For example, negative pressure or suction can be applied by the expandable member to the tissue lumen (e.g., the duodenum, duodenal tissue) to facilitate tissue apposition with the expandable member's electrode array. Higher tissue apposition can further enable reduced total energy delivery and improved treatment outcomes.

[0249] In some variations, the range of tissue thicknesses can be reduced by stretching the tissue using an expandable member to apply a radially outward force and / or by applying negative pressure from the expandable member to the tissue, as shown in Figure 71 A. For example, the expandable member can stretch the tissue such that the ratio of the manipulated (e.g., compressed / stretched / expanded) tissue thickness to the unmanipulated tissue thickness is about 0.5.

[0250] 71C and 71D are cross-sectional images of an undistracted (e.g., unstretched) duodenum. 71E and 71F are cross-sectional images of a distended (e.g., stretched) duodenum. In some variations, the resection devices described herein can transition to an expanded configuration to expand (e.g., stretch, elongate) tissue during a treatment procedure. In some variations, tissue can be treated within a predetermined range of expansion ratios. In some variations, the ratio of expanded mucosal tissue to undistracted mucosal tissue can be about 0.40 to about 0.60, about 0.45 to about 0.55, and about 0.50, including all ranges and subvalues ​​therebetween. In some variations, the ratio of expanded submucosal tissue to undistracted submucosal tissue can be about 0.15 to about 0.35, about 0.20 to about 0.30, and about 0.26, including all ranges and subvalues ​​therebetween. In some variations, the ratio of distended duodenal diameter to undistended duodenal diameter can be about 1.5 to about 2.3, about 1.7 to about 2.1, and about 1.91, including all ranges and subvalues ​​therebetween. In some variations, the ratio of distended duodenal diameter to undistended duodenal diameter can be about 1.5 to about 2.3, about 1.7 to about 2.1, and about 1.91, including all ranges and subvalues ​​therebetween.

[0251] In some variations, the ablation device can be configured to simultaneously expand tissue and aspirate it into the ablation device. In some variations, the ratio of aspirated and expanded mucosal tissue to unexpanded mucosal tissue can be about 0.40 to about 0.60, about 0.45 to about 0.55, and about 0.47, including all ranges and subvalues ​​therebetween. In some variations, the ratio of aspirated and expanded submucosal tissue to unexpanded submucosal tissue can be about 0.20 to about 0.50, about 0.30 to about 0.40, and about 0.33, including all ranges and subvalues ​​therebetween.

[0252] In some variations, suction can be applied by the device itself while in the expanded configuration. Additionally or alternatively, suction can be applied by a visualization device, such as an endoscope. The amount of suction can be configured to ensure tissue apposition to the surface of the expandable member (e.g., the electrode surface). However, the amount of suction should not exceed a predetermined threshold corresponding to pressure necrosis. In some variations, the negative pressure (e.g., suction) applied to the tissue can be from about 50 mmHg to about 75 mmHg for less than about 1 minute. In some variations, the negative pressure (e.g., suction) applied to the tissue can be from about 10 mmHg to about 200 mmHg. The amount of suction can be a function of one or more of the total surface area of ​​the expandable member, the number and size of the openings, the time the suction is applied, the condition of the opening edges, the compliance of the tissue, the vascularization of the tissue, and the fragility of the tissue.

[0253] In some variations, the amount of tissue compliance may correspond to the amount of expansion and suction necessary to ensure uniform electrode surface contact and desired tissue treatment. In some variations, tissue may respond better to less expansion and more suction (or vice versa), depending on compliance and structure. In some variations, apposition can be assessed visually and / or through impedance measurements. In some variations, apposition can be measured using one or more temperature and / or pressure sensors.

[0254] The introduction and advancement of various devices into the duodenum is illustrated in the schematic diagrams of FIGS. 55A-55F, in which the gastrointestinal tract (5500) comprises a stomach (5510), a pylorus (5520), and a duodenum (5530). FIG. 55B shows a visualization device (e.g., an endoscope) (5540) being advanced through the stomach (5510) and into the duodenum (5530). The visualization device (5540) can be configured to image tissue, pulsed electric field devices, and visual markers (e.g., anatomical landmarks, thermal markers, fiducials) to aid in location determination. For example, the imaged tissue can be used to identify the tissue as one or more of treated, marked, affected, untreated, etc. FIG. 55C shows a guidewire (5560) advanced through the stomach (5510) and into the duodenum (5530). In some variations, as shown in FIG. 55D, a visualization device (5540) can be advanced over a guidewire (5530) into the duodenum (5530). In some variations, as shown in FIG. 55D, a treatment device (5560) can be advanced over a guidewire (5560) positioned with the visualization device (5540) into the duodenum (5530). FIGS. 56A-56H are detailed perspective views of a pulsed electric field device (5650) and visualization device (5640) within the duodenum (5630), as described in more detail herein with respect to methods for treating diabetes. FIGS. 81A-81C are schematic illustrations of another variation of a method for treating diabetes, as described in more detail herein. FIGS. 82A-82D are images corresponding to the method shown in FIGS. 81A-81C.

[0255] FIG. 54 is a flowchart generally illustrating a variation of a method (5400) for treating diabetes. The method (5400) may include advancing a pulsed electric field device comprising an expandable member comprising an electrode array toward a first portion of the duodenum (5402). For example, FIG. 55E shows a pulsed electric field device (5550) advanced over a guidewire through the stomach (5510) and into the duodenum (5530). Similarly, a visualization device may be advanced into the duodenum. FIG. 55F shows a visualization device (5540) (e.g., an endoscope) advanced into the duodenum (5530) alongside (e.g., substantially parallel to) the pulsed electric field device (5550). In FIG. 56A, a pulsed electric field device (5650) comprises an expandable member (5652) in a compressed configuration within the duodenum (5630). For example, the expandable member (5652) is in a wound configuration comprising multiple turns around the longitudinal axis of the pulsed electric field device (5650). In the compressed configuration, the expandable member (5652) may comprise a lumen having a first inner diameter. The visualization device (5640) may be operated independently of the pulsed electric field device (5650). Similarly, FIG. 81A illustrates a method (8100) for treating diabetes including a pulsed electric field device (8120) comprising an expandable member (8130) and a visualization device (8140) advanced into the duodenum (8110) along a guidewire (8122). In some variations, one or more of the device (8120) and the visualization device (8140) may be disposed distal to the papilla. FIG. 82A is an image of the expandable member (8220) of a pulsed electric field device from the perspective of the distal end of a visualization device (e.g., an endoscope). The expandable member (8220) can be in a compressed configuration when advanced through the duodenum (8210).

[0256] In step 5404, the expandable member of the pulsed electric field device or modulated electric field device may transition from a compressed configuration to an expanded configuration, for example, to engage tissue and / or allow a visualization device to advance through the lumen of the expandable member. As shown in the expanded configuration in FIG. 56B , the expandable member (5652) may include a lumen having a second inner diameter larger than the first inner diameter. In some of these variations, the visualization device (5640) may advance through the lumen of the expandable member (5652) in the expanded configuration, allowing the visualization device (5640) to visualize, for example, the tissue (5600) and a distal portion of the pulsed electric field device (5650). Additionally or alternatively, the pulsed electric field device (5650) may include a second expandable member (e.g., an inflatable member, balloon) (not shown) disposed distal to the expandable member (5652). In some of these variations, the second expandable member can be expanded to assist in one or more of advancing, positioning, and visualizing the pulsed electric field device (5650) and tissue (5630). For example, one or more portions of the second expandable member can be transparent to allow a visualization device to see through the second expandable member.

[0257] As shown in FIG. 56B, the expandable member (5652) can be deployed through one or more turns to transition the expandable member (5652) to an expanded configuration (e.g., a deployed configuration). As shown in FIG. 56C, the pulsed electric field device (5650) can include a first elongate body (5654) and a second elongate body (5656) positioned within the first elongate body (5654). The expandable member (5652) can be wrapped around the second elongate body (5656) a predetermined number of turns. In some of these variations, the second elongate body (5656) can be rotated relative to the first elongate body (5654) to deploy the expandable member (5652) and bring the expandable member into contact with the duodenum (5630). Full circumferential contact between the expandable member (5652) and the duodenum (5630) can improve energy delivery and treatment outcomes. For example, Figure 64B is an image of a deformed pulsed electric field device (6400) in a deployed configuration within a tissue lumen (6430) imaged with a visualization device retracted relative to the pulsed electric field device (6400) to allow visualization of the proximal end of the expandable member (6410) and the tissue (6430).

[0258] In some variations, as shown in FIG. 81B, the expandable member (8130) of the device (8120) may transition to an expanded configuration and contact tissue. In some variations, the distal end of the visualization device (8120) may be disposed either within the lumen of the expandable member (8130), proximal to the proximal end of the expandable member (8130), or distal to the distal end of the expandable member (8130). As shown in FIG. 81B, the visualization device (8120) may be configured to generate negative pressure (e.g., suction) within the lumen of the expandable member (8130) that draws the tissue (8110) onto the surface of the expandable member (8130). Additionally or alternatively, the device (8120) may be configured to generate negative pressure to draw the tissue (8110) onto the surface of the expandable member (8130). In some variations, suction can be applied during delivery of the pulsed waveform and reduced during periods when pulsed electric field energy is not being delivered. For example, suction can be reduced (or stopped) when the tissue is cooling after energy delivery and when one or more of the device (8130) and visualization device are advancing within the tissue (8110). Thus, suction can be applied intermittently throughout the treatment process. The amount of suction applied to one or more portions of the tissue can be as described herein.

[0259] Figure 82B is an image of the expandable member (8220) in an expanded configuration, with the expandable member (8220) in contact with the duodenum (8210). Figure 82C is an image of tissue (8210) in contact with the expandable member (8220) after applying negative pressure as described herein. In Figure 82C, the tissue is pulled through multiple openings (8222) extending through the thickness of the expandable member (8220). Intimate contact between the tissue (8210) and the expandable member (8220) can improve energy delivery and treatment outcomes. One or more pulse waveforms can be delivered while suction is applied.

[0260] In step 5406, one or more pulse waveforms can be delivered to the electrode array of the expandable member to generate a pulsed or modulated electric field. For example, FIG. 56C shows the expandable member (5652) in an expanded configuration with electrodes (not shown) configured to receive the pulse waveforms to generate a pulsed or modulated electric field for treating the duodenum (5630). In some variations, one or more of the visualization member (5640) and the pulsed electric field device (5650) can be configured to apply suction or negative pressure to the tissue to increase apposition of the tissue (5630) to the expandable member (5652) electrode array. In some variations, fluid can be drawn or aspirated between the pulsed electric field device and the duodenum from the expandable member. For example, suction or negative pressure can be applied by the visualization device.

[0261] In some variations, the pulse waveform comprises a frequency of about 250 kHz to about 950 kHz, about 250 kHz to about 950 kHz, or about 350 kHz, inclusive of all ranges and subvalues ​​therebetween, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A or about 0.6 A to about 65 A per square centimeter of tissue. For example, the current density can be about 0.6 A to about 100 A, or about 0.6 A to about 65 A per square centimeter of tissue from the electrode array.

[0262] In some variations, the pulse waveform may comprise about 1 to about 100 pulse groups, with about 1 to about 100 pulses per group. In some of these variations, the pulse waveform may comprise a group delay of about 10 μs to about 2000 μs or about 10 μs to about 500 μs and an evacuating rate of about 50 ms to about 4000 ms or about 50 ms to about 500 ms. In some variations, the pulsed or modulated electric field generated by the pulsed electric field device (5650) varies spatially within the tissue (5360) by up to about 20% at a given treatment distance from the expandable member (5652). For example, at a 4 cm depth of the duodenum,2 Treatment of a treatment area of ​​approximately 81,000 watts or approximately 20,250 watts / cm 2 , or about 1,800 watts / cm 2 The voltage may include delivering about 900 V applied to 10 Ω or about 600 V applied to 50 Ω, respectively, for an instantaneous power of about 0.04 Joules / cm 2 for about 2 μs, or about 27 Joules / cm for a corresponding dose of 2 In some variations, the treatment pulse may be repeated about 1000 times to equal about 40.5 Joules of total energy. For example, about 400 cm 2 As another example, a treatment area of ​​about 100 cm of duodenum may be provided with a dose of about 16,200 J. 2 A treatment area of ​​the duodenum may provide a dose of approximately 27 kJ.

[0263] In some variations, the pulse waveform delivered to a portion (e.g., section) of tissue may comprise multiple pulse waveforms, i.e., the portion may be treated multiple times (e.g., two, three, four times).

[0264] In some variations, a temperature sensor may measure the temperature of the tissue and use that temperature to inhibit delivery of the pulse waveform, thereby adding a margin of safety to the procedure. In step 5408, the temperature of the tissue may be measured using a temperature sensor. For example, the temperature may be measured at least during delivery of the pulse waveform or immediately after each packet of energy. In step 5410, the delivery of the pulse waveform may be adjusted in response to the measured temperature. For example, if the measured temperature exceeds a predetermined threshold, the delivery...

Claims

1. 1. An apparatus comprising: a first elongate body having a lumen; a second elongate body positioned at least partially within the lumen; and an expandable member wrapped around the second elongate body, the expandable member comprising an inner end coupled to the second elongate body, an outer end coupled to the first elongate body, and an electrode array; an actuator coupled to the expandable member, the actuator comprising one or more of a gear and a friction roller coupled to an exterior surface of the second elongate body, the expandable member comprising a track configured to couple to the one or more of the gear and the friction roller, and rotation of the actuator deploys the expandable member; An apparatus comprising:

2. The device of claim 1 , wherein the expandable member includes a plurality of turns around the second elongate body.

3. The device of claim 1 , further comprising a connector coupling the first elongate body to the outer end of the expandable member.

4. 10. The device of claim 1, wherein the second elongate body is configured to rotate relative to the first elongate body to transition the expandable member between a rolled configuration and a deployed configuration.

5. The device of claim 4 , wherein the expandable member comprises a lumen having a diameter of at least 10 mm in the deployed configuration.

6. 1. A system for treating tissue of a patient, comprising: An apparatus according to claim 5; a third elongate body disposed within the lumen of the expandable member; and A system comprising:

7. The system of claim 6 , wherein the third elongate body comprises an endoscope.

8. 10. The device of claim 1, further comprising a distal dilator and a proximal dilator coupled to one of the first elongate body and the second elongate body, the expandable member being disposed between the distal dilator and the proximal dilator.

9. The device of claim 1 , wherein the track comprises a plurality of spaced openings in the expandable member.

10. 10. A system comprising the apparatus of claim 1, further comprising a signal generator coupled to the electrode array, the signal generator configured to generate a pulse waveform comprising a frequency of about 250 kHz to about 950 kHz, a pulse width of about 0.5 μs to about 4 μs, a voltage applied by the electrode array of about 100 V to about 2 kV, and a current density from the electrode array of about 0.6 A to about 100 A per square centimeter of tissue.

11. 10. The device of claim 1, wherein the electrode array is configured to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm.

12. The device of claim 1 , wherein the expandable member defines one or more openings therethrough.

13. 10. The device of claim 1, wherein the electrode array is configured to generate a therapeutic electric field, the therapeutic electric field treating a predetermined set of cell types and not treating muscle tissue.

14. The device of claim 1 , wherein the electrode array is configured to generate a therapeutic electric field that treats cells but leaves a tissue scaffold intact.

15. 10. The device of claim 1, wherein the electrode array comprises a plurality of elongated electrodes with a ratio of center-to-center distance between adjacent electrodes to width of the electrodes of about 2.3:1 to about 3.3:

1.

16. 16. The device of claim 15, wherein the plurality of elongated electrodes includes a first electrode and a second electrode, the second electrode being parallel to the first electrode or interdigitated with the first electrode.

17. 16. The apparatus of claim 15, wherein the center-to-center distance between adjacent electrodes and the widths of the elongated electrodes are substantially equal.

18. 16. The apparatus of claim 15, wherein at least one of the plurality of elongated electrodes comprises a semi-elliptical cross-sectional shape.

19. 16. The device of claim 15, wherein the ratio of electrode height to electrode width is from about 1:4 to about 1:

8.

20. 16. The device of claim 15, wherein the plurality of adjacent electrodes are spaced apart by a weighted average distance of about 0.3 mm to about 6 mm.

21. The device of claim 15, wherein the surface area of ​​the plurality of electrodes comprises about 20% to about 45% of the surface area of ​​the expandable member in a given configuration.

22. 1. A system comprising: a first elongate body having a lumen; a second elongate body positioned at least partially within the lumen; and an expandable member wrapped around the second elongate body, the expandable member having an inner end coupled to the second elongate body and an outer end coupled to the first elongate body, the expandable member coupled to the first elongate body, the expandable member having a compressed configuration and an expanded configuration, the expandable member further comprising an electrode array comprising a plurality of electrodes; an actuator coupled to the expandable member, the actuator comprising one or more of a gear and a friction roller coupled to an outer surface of the second elongate body, the expandable member comprising a track configured to couple to the one or more of the gear and the friction roller; a signal generator coupled to the electrode array, the signal generator configured to deliver a pulsed or modulated electric field waveform to the electrode array to generate a therapeutic electric field at a first tissue depth of about 1 mm and a non-therapeutic electric field at a second tissue depth of at least about 1.5 mm; A system comprising:

23. 23. The system of claim 22, wherein a ratio of a center-to-center distance between adjacent electrodes of the electrode array to a width of at least one electrode of the plurality of electrodes is between about 2.3:1 and about 3.3:

1.

24. 23. The system of claim 22, wherein the pulsed electric field waveform comprises a frequency of about 350 kHz to about 500 kHz, a pulse width of about 0.5 μs to about 4 μs, and a voltage of about 400 V to about 750 V applied by the electrode array.

25. 25. The system of claim 24, wherein the signal generator generates a drive voltage of about 500V to about 750V delivered to the electrode array.

26. The device of claim 12 , wherein the one or more openings are configured for one or more of fluid ejection, fluid aspiration, and tissue aspiration.

27. The device of claim 12, wherein the device is configured for application of suction through the expandable member from about 10 mmHg to about 200 mmHg.

28. The device of claim 1 , wherein the expandable member is wrapped around the second elongate body or the gear.

29. 23. The system of claim 22, wherein the expandable member is wrapped around the second elongate body or the gear.

30. 23. The system of claim 22, wherein the track comprises a plurality of spaced openings in the expandable member.

Images