Devices and methods for delivering electroporation therapy

Abstract

To provide, generally, medical devices, and particularly, medical devices for delivering electroporation therapy.SOLUTION: An electroporation device includes a shaft 214 and a conformable electrode assembly 220. The shaft 214 includes a proximal end and a distal end, where the conformable electrode assembly 220 is located at the distal end of the shaft 214. The electrode assembly 220 has a first side 244 and a second side 252, where the first side 244 includes a first non-conductive portion 248 and a first electrode 246 that is centrally located on the first side 244. The first non-conductive portion 248 is defined by a first surface area, and the first electrode 246 is defined by a second surface area, where the first surface area is greater than the second surface area.SELECTED DRAWING: Figure 2a

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the priority of U.S. Provisional Application No. 63 / 040,751, entitled "DEVICE AND METHOD FOR DELIVERING ELECTROPORATION THERAPY", filed on June 18, 2020, which is incorporated herein by reference.

[0002] The present invention generally relates to medical devices, and more particularly to medical devices for delivering electroporation therapy.

[0003] Electroporation therapy involves applying an electric field to a cell membrane to increase its permeability. In some applications, electroporation is used to permanently damage or destroy target cells, which is called irreversible electroporation (IRE) therapy. One advantage of IRE therapy is that it can damage or excise target cells without affecting adjacent cells. IRE therapy is applicable to any procedure where ablation of tissue is desired, including, for example, cancer treatment and / or cardiac ablation therapy for alleviating / stopping certain arrhythmia conditions, including atrial fibrillation, atrial flutter, and atrial tachycardia.

[0004] In particular, IRE therapy serves as an alternative to conventional cardiac ablation techniques. The main cause of atrial arrhythmia is suspected to be vagus electrical signals in the left or right atrium of the heart. Conventional cardiac ablation therapy requires the delivery of ablation energy (e.g., radiofrequency (rf) energy, laser, etc.) to heart tissue. The ablation energy, i.e., thermal energy, damages heart tissue and destroys unwanted electrical pathways that cause arrhythmia conditions.

[0005] IRE therapy allows for targeted ablation of cardiac tissue to create desired damage without introducing the thermal energy associated with conventional ablation treatments, thus enabling the destruction of undesirable electrical pathways. [Overview of the Initiative]

[0006] According to one embodiment, the electroporation device includes a shaft having a proximal end and a distal end, and a adaptable electrode assembly disposed at the distal end of the shaft. The electrode assembly includes a first surface and a second surface, the first surface including a first nonconductive portion and a first electrode disposed in the center of the first surface, the first nonconductive portion being defined by a first surface area, and the first electrode being defined by a second surface area, the first surface area being greater than the second surface area.

[0007] In another embodiment, a method for delivering electroporation therapy includes the step of introducing a catheter shaft having a compatible electrode assembly to a target site in a patient. The method may further include the step of positioning a first surface of the compatible electrode assembly in contact with the target tissue, the first surface of the compatible electrode assembly may include a first nonconductive portion and a first electrode positioned in the center of the first surface, the first nonconductive portion surrounding the first electrode. The method may further include the step of delivering electroporation pulses to the first electrode.

[0008] In another embodiment, the electroporation treatment system may include a catheter and an electroporation generator. The catheter may further include a handle, a compatible electrode assembly, and a shaft connected to the handle at its proximal end and to the electrode assembly at its distal end. The compatible electrode assembly may include a first surface and a second surface opposite the first surface, the first surface including a first nonconductive portion and a first electrode attached to the first nonconductive portion, the first electrode being centrally positioned and the nonconductive portion surrounding the first electrode in a plane defined by the first surface. The electroporation generator may be connected to the catheter to deliver electroporation pulses to the first electrode. [Brief explanation of the drawing]

[0009] [Figure 1] This is a block diagram of a medical system for providing electroporation therapy, according to several embodiments. [Figure 2a] This is an isometric view of a catheter and compatible electrode assembly for delivering electroporation therapy according to several embodiments. [Figure 2b] This is an isometric view of a catheter and compatible electrode assembly positioned adjacent to selected tissue for delivering electroporation therapy, according to several embodiments. [Figure 3a] These are isometric views of a non-conductive material and a first electrode and a second electrode separated by the non-conductive material, according to several embodiments. [Figure 3b] This is a side view of a non-conductive material that separates a first electrode and a second electrode according to several embodiments. [Figure 3c] This is a top view of a first surface of a nonconductive material and a first electrode according to several embodiments. [Figure 3d] These are cross-sectional views of a non-conductive material, a first electrode, and a second electrode according to several embodiments. [Figure 4a]This is a top view of the non-conductive portion of a compatible electrode assembly according to several embodiments. [Figure 4b] This is a top view of the non-conductive portion of a compatible electrode assembly according to several embodiments. [Figure 4c] This is a top view of the non-conductive portion of a compatible electrode assembly according to several embodiments. [Figure 5] This is an isometric view of a catheter and a compatible electrode assembly, including a central electrode and multiple peripheral electrodes, according to several embodiments. [Figure 6a] This is an isometric view of a suitable electrode assembly related to several embodiments. [Figure 6b] This is a cross-sectional view of a compatible electrode assembly according to several embodiments. [Figure 6c] This is an isometric view of a circuit board in which a central electrode and multiple peripheral electrodes are arranged, according to several embodiments. [Figure 7a] This is a side view of a catheter and a compatible electrode assembly according to several embodiments. [Figure 7b] This is a top view of a catheter and a compatible electrode assembly according to several embodiments. [Figure 8] This flowchart illustrates a method for delivering irreversible electroporation therapy (IRE) according to several embodiments. [Modes for carrying out the invention]

[0010] The disclosed invention relates to a medical device comprising a catheter and a compatible electrode assembly. The first surface of the compatible electrode assembly includes a first electrode positioned in the center of a compatible nonconductive portion. The surface area of ​​the nonconductive portion is larger than the surface area of ​​the first electrode, and thus the nonconductive portion extends around the first electrode. In some embodiments, the nonconductive portion and the first electrode are located substantially coplanar, and the nonconductive portion surrounds the first electrode in a defined plane. The presence of the nonconductive portion surrounding the first electrode ensures that the conductive path formed between the first electrode and the second electrode during electroporation treatment includes tissue adjacent to the first surface of the compatible electrode assembly.

[0011] Figure 1 is a schematic block diagram of a system 100 for providing electroporation therapy according to several embodiments. The system 100 includes a catheter 102, an electroporation generator 104, a computer system 106, an input / output unit 108, and a display 110. The catheter 102 includes a handle 112 and a shaft 114 having a distal end 116 and a proximal end 118. A adaptable electrode assembly 120 is positioned at the distal end 116 of the shaft 114 and is configured to deliver electroporation therapy to adjacent tissue 122. In the embodiment shown in Figure 1, the adaptable electrode assembly 120 is positioned to deliver electroporation therapy to cardiac tissue within the heart, but in other embodiments, the distal end 116 of the catheter 102, including the electrode assembly 120, may be positioned elsewhere in the body to deliver the desired electroporation therapy. The handle 112 is used to guide the distal end 116 of the shaft 114 to the desired location in the body. In some embodiments, the distal end 116 of the shaft includes one or more sensors (e.g., magnetic, optical, electrical, etc.) used to visualize the distal end 116 and / or to navigate the distal end 116 to a desired location within the body.

[0012] The electroporation pulses delivered by the electrode assembly 120 are generated by the electroporation generator 104. In some embodiments, the magnitude, duration, and number of pulses delivered may be modified by the electroporation generator 104. The electroporation generator 104 is connected to the interface connector 124 of the catheter 102 via a cable 126. The electroporation pulses delivered to the handle 102 are transmitted to the electrode assembly 120 via the shaft 114. In addition, in some embodiments, the catheter 102 includes one or more sensors (e.g., magnetic, electrical, optical, etc.) positioned along the shaft 114 to provide sensor input to the computer system 106. In some embodiments, the same electrodes used to generate the electroporation pulses are also used to collect electrical signals (e.g., electrocardiogram signals, impedance signals, etc.) and thus provided to the computer system 106 via the electroporation generator 104. In other embodiments, the sensed signal, whether electrical, magnetic, or optical, may be provided directly to the computer system 106 (i.e., the cable 126 may be connected directly to the computer system 106 rather than via the electroporation generator 104).

[0013] In some embodiments, the computer system 106 includes a storage device 128 capable of storing computer-readable instructions and an electronic control unit (ECU 130) capable of executing computer-readable instructions. In some embodiments, the computer system 106 communicates bidirectionally with an input / output unit 108 and further displays information via a display 110. In some embodiments, the computer system 106 controls the generation and delivery of electroporation pulses by an electroporation generator 104. This may include changing one or more of the amplitude (i.e., intensity), duration, and number of pulses delivered by the electroporation generator 104.

[0014] Furthermore, computer system 106 may utilize one or more sensed signals, regardless of whether electrical, magnetic, or optical, as an input enabling one or more functions including visualization, navigation, and / or mapping. For example, one or more sensed signals may be utilized to visualize the position of a catheter within a patient's body and to facilitate navigation of the catheter to a desired location within the patient's body via the patient's vasculature. In some embodiments, electrical signals (e.g., electrocardiogram signals) sensed by electrodes disposed on electrode assembly 120 may be utilized to map the propagation of electrical signals within a patient's heart or to confirm that a signal of interest has been blocked following delivery of an electroporation pulse. In some embodiments, surface electrodes 134 are utilized to receive electrical signals and / or to provide electrical signals to the body that are to be received by one or more electrodes disposed on electrode assembly 120. For example, electrical signals generated by surface electrodes 134 (or two or more surface electrodes) may be detected by one or more electrodes disposed at the distal end 116 of catheter 102 within a patient's body. In other embodiments, surface electrodes 134 may function as a return path for electrical signals delivered to electrode assembly 120, such as a return path for an electroporation pulse delivered to electrode assembly 120 by electroporation generator 104.

[0015] In some embodiments, one or more sensed signals are utilized to confirm the position of electrode assembly 120 relative to tissue targeted for electroporation. In particular, in some embodiments, one or more sensed signals are utilized to confirm that a first surface of a conformable electrode assembly including at least a first electrode and a non-conductive material surrounding the first electrode is in contact with tissue. Physical contact between the first surface of a non-conformable electrode assembly and tissue selected to receive electroporation treatment ensures that the conductive path formed between the first electrode and a second electrode includes tissue adjacent to the first electrode.

[0016] Referring here to Figures 2a and 2b, one embodiment of the adaptable electrode assembly 220 is shown in more detail. In some embodiments, the adaptable electrode assembly 220 is located at the distal end 216 of the shaft 214 and includes a first surface 244 and a second surface 252 opposite the first surface 244. In some embodiments, the first surface 244 includes a non-conductive portion 248 having a first surface area and a first electrode 246 centered relative to the non-conductive portion 248 and having a second surface area smaller than the first surface area. That is, the non-conductive portion 248 surrounds the first electrode in the plane defined by the first surface 244 or extends from the first electrode to the edge of the adaptable electrode assembly 220. The upper surface of the first electrode 246 (i.e., the upper surface of the first electrode that will be in contact with the tissue to be treated) is exposed. Furthermore, in some embodiments, the electrode assembly 220 includes one or more ring electrodes 240, 242 disposed on the shaft 214. In some embodiments, a second electrode may also be disposed on the second surface 252 of the adaptable electrode assembly 220 (as shown in Figure 2b). In other embodiments, the second surface 252 of the adaptable electrode assembly 220 does not include a second electrode.

[0017] As shown in Figure 2a, the first electrode 246 is positioned in the center of the first surface 244 of the adaptable electrode assembly 220. In some embodiments, the first electrode 246 and the nonconductive portion 248 together provide a relatively flat surface. In some embodiments, the nonconductive portion 248 includes a recess for housing the first electrode 246, and the first electrode 246 is surrounded by the nonconductive portion 248 on all surfaces except the surface that will be in contact with the tissue. In some embodiments, the first electrode 246 is mounted within the recess of the nonconductive portion 248, and the upper surfaces of the first electrode 246 and the nonconductive portion 248 are relatively flat. In some embodiments, the first electrode 246 is recessed within the nonconductive portion 248, and the nonconductive portion 248 is raised or protruding relative to the first electrode 246. In some embodiments, the first electrode 246 is mounted on the nonconductive portion 248 such that the first electrode 246 protrudes from the nonconductive portion 248.

[0018] In some embodiments, the presence of a non-conductive portion 248 surrounding the first electrode 246 ensures that the conductive path formed between the first electrode 246 and the second electrode (wherever it may be located) includes tissue adjacent to the first electrode 246. That is, contact between the non-conductive material 248 surrounding the first electrode 246 and the adjacent tissue ensures that the conductive path formed between the first electrode 246 and the second electrode includes tissue adjacent to the first electrode 246. If there is no non-conductive portion 248 surrounding the first electrode 246, and / or if the non-conductive portion 248 does not contact the tissue surrounding the first electrode 246, a conductive path may be formed that bypasses the tissue adjacent to the first electrode 246 via a blood pool adjacent to the first electrode 246. As a result, the electric field applied to the selected tissue may be reduced, which may decrease the effectiveness of the electroporation treatment. Therefore, it is desirable that the non-conductive portion 248 that comes into contact with the tissue be larger in size than the surface of the first electrode 246, and that the non-conductive portion 248 that surrounds the first electrode 246 and comes into contact with the tissue ensure that it includes tissue adjacent to the electrode assembly 220 to which the conductive path formed between the first electrode 246 and the second electrode can be adapted. For this purpose, in some embodiments, the non-conductive portion 248 is made of a flexible material such as silicon, and the shape of the non-conductive portion 248 can be changed to conform to the geometric shape of the tissue being treated. In other embodiments, many other suitable materials, including, for example, Pebax, nylon, and rubber, may be used for the non-conductive portion 248. In other embodiments, the non-conductive portion 248 may be made of a more rigid material. In some embodiments, the first surface 244, which includes at least the non-conductive portion 248, is relatively flat when there is no external force (i.e., when the first surface is not pressed against the tissue). In other embodiments, the first surface 244, which includes at least the non-conductive portion 248, has a geometric shape other than a plane when no external force is present. For example, the first surface 244 may have a concave or convex shape.In some embodiments, in order to ensure contact between the non-conductive material 248 and the corresponding tissue, a flexible non-conductive material 248 may be utilized by using a geometric shape other than planar on the first surface 244. That is, since the non-conductive material 248 can bend and conform to the tissue, the contact between the non-conductive material 248 and the tissue in the region surrounding the first electrode 246 is ensured.

[0019] Furthermore, as shown in FIG. 2b, in some embodiments, the electrode assembly 220 is connected to the shaft 214 via a hinge 258, and the hinge 258 can change or deflect the orientation of the main plane defined by the electrode assembly 220 with respect to the shaft 214. In some embodiments, the deflection of the electrode assembly 220 is controlled by an operator via a handle 112 (shown in FIG. 1). In other embodiments, the deflection of the electrode assembly 220 depends on the force applied to the electrode assembly 220 when it is brought into contact with adjacent tissue. Thus, the hinge 218 helps the first surface 244 to contact the tissue 250 to be treated.

[0020] During electroporation treatment, the first surface 244 is positioned to be in contact with the tissue 250 (e.g., cardiac tissue) selected to receive electroporation treatment. Electroporation pulses or a series of pulses are delivered between the first electrode 246 and the second electrode, with one electrode acting as the anode and the other as the cathode. A conductive path is formed between the first electrode 246 and the second electrode. For example, in the embodiment shown in Figure 2b, the second electrode may be realized by an electrode 254 positioned on the second surface 252 of a compatible electrode assembly 220. The non-conductive portion 248 surrounding the first electrode 246 ensures that the conductive path includes the tissue 250 adjacent to the first electrode 246. That is, the non-conductive portion 248 prevents the formation of a conductive path between the first electrode 246 and the second electrode 254 that does not include the tissue 250 adjacent to the first electrode 246. In the embodiment shown in Figure 2b, the second surface 252 of the adaptable electrode assembly 220 is substantially symmetrical to the first surface 244 (shown in Figure 2a). This is beneficial because, in some embodiments, either the first surface 244 or the second surface 252 only needs to be in contact with the tissue to be treated. In some embodiments, the determination of which electrode should be used as the anode and which as the cathode is made depending on which of the first electrode 246 and the second electrode 254 is in contact with the tissue 250. However, in other embodiments, whether the electrode in contact with the tissue 250 is the anode or the cathode does not affect the effectiveness of the electroporation treatment.

[0021] In some embodiments, the second surface 252 does not have to be symmetrical with respect to the first surface 244. For example, in some embodiments, only the first surface 244 is always in contact with the tissue 250 to be treated. In this case, the second electrode 254 does not need to be surrounded by the non-conductive material 256. As a result, the position and size of the second electrode 254 can be changed as desired. For example, the second electrode 254 may be positioned at a different location along the second surface 252, or it may encompass the entire surface area of ​​the second surface 252. In yet another embodiment, the second electrode does not have to be positioned on the second surface 252. For example, in some embodiments, the role of the second electrode as either a cathode or anode to the first electrode 246 is provided by a ring electrode 240 or 242. In yet another embodiment, the role of the second electrode is provided by a surface electrode 134 shown in Figure 1. In another embodiment, the second electrode may be positioned on a separate catheter or medical device. As will be described in more detail below, in some embodiments, one or both of the first electrode 246 and the second electrode 254 may be used to perform functions other than the delivery of electroporation pulses. For example, these other functions may include one or more of the mapping, navigation, and / or visualization of the medical device.

[0022] Referring here to Figures 3a to 3d, adaptable electrode assemblies 320 according to several embodiments are shown. In particular, Figure 3a is an isometric view of the adaptable electrode assembly 320, Figure 3b is a side view of the adaptable electrode assembly 320, Figure 3c is a top view of the adaptable electrode assembly 320, and Figure 3d is a cross-sectional view along line dd in Figure 3b. In some embodiments, the adaptable electrode assembly 320 includes a first nonconductive portion 360, a second nonconductive portion 362, an intermediate nonconductive portion 364, a first electrode 346, and a second electrode 354. In this embodiment, the first electrode 346 is mounted in a recess of the first nonconductive portion 360, as shown in Figures 3b and 3d, forming a substantially flat surface. Similarly, the second electrode 354 is mounted in a recess of the second nonconductive portion 362, forming a substantially flat surface. As described above, in other embodiments, the first electrode 346 and / or the second electrode 354 may be more recessed, and the first nonconductive portion 360 and / or the second nonconductive portion 362 may be raised relative to the corresponding electrodes. In particular, in some embodiments, the first nonconductive portion 360 and / or the second nonconductive portion 362 may be flexible and / or compressible, in which case it may be desirable that the first electrode 346 and the second electrode 354 be recessed from the upper part of the corresponding nonconductive portion 360 and nonconductive portion 362.

[0023] In some embodiments, the first electrode 346 and / or the second electrode 354 may protrude from the upper surfaces of the corresponding nonconductive portions 360 and 362. In some embodiments, the presence of an intermediate nonconductive portion 364 causes the first nonconductive portion 360 to be separated from the second nonconductive portion 362. In some embodiments, the intermediate nonconductive portion 364 provides electrical insulation between the first electrode 346 and the second electrode 354. In the embodiments shown in Figures 3a to 3d, the first nonconductive portion 360 and the second nonconductive portion 362 have a cylindrical shape and a diameter greater than the diameter of the intermediate nonconductive portion 364. In some embodiments, as shown in Figure 3d, the difference in diameter creates a space 366 defined by the distance w between the first nonconductive portion 360 and the second nonconductive portion 362. In some embodiments, the space 366 formed between the first nonconductive portion 360 and the second nonconductive portion 362 is configured to receive features for attaching a compatible electrode assembly 320 to the shaft of the catheter.

[0024] In some embodiments, the first nonconductive portion 360 and the second nonconductive portion 362 are flexible. In some embodiments, the intermediate nonconductive portion 364 is made of the same material as the first nonconductive portion 360 and the second nonconductive portion 362. However, in other embodiments, the intermediate nonconductive portion 364 is made of a different nonconductive material having higher or lower flexibility than the first nonconductive portion 360 and the second nonconductive portion 362. For example, in some embodiments, the first nonconductive portion 360 and the second nonconductive portion 362 may be made of one or more of silicon, Pebax, nylon, and / or rubber, and the intermediate nonconductive portion 364 may be made of polyimide circuit material. In some embodiments, the first nonconductive portion 360 and the second nonconductive portion 362 may be fitted to a shaft tube (i.e., they may be wound up). When removed from the shaft, the first conductive part 360 and the second conductive part 362 return to a desired shape, such as a planar shape as shown in Figures 3a to 3d. In other embodiments, the desired shape (i.e., when there is no external force) may be another shape, such as a concave shape or a convex shape.

[0025] As shown in Figure 3c, the first nonconductive portion 360 surrounds the first electrode 346, and the surface area of ​​the first nonconductive portion 360 (including the recess that holds the first electrode 346) is larger than the surface area of ​​the first electrode 346. In the embodiments shown in Figures 3a to 3d, both sides of the electrode assembly are symmetrical, so the same applies to the second nonconductive portion 362 and the electrode 354. As described above, in some embodiments, the second surface 352 is not positioned in contact with tissue for the purpose of providing treatment, in which case the geometric shapes of the second electrode 354 and the second nonconductive portion 362 may be modified (for example, the position of the second electrode 354 on the second surface 352 may be changed, the size of the second electrode 354 may be enlarged to the total surface area of ​​the second surface 354, etc.).

[0026] The cross-sectional view shown in Figure 3d shows the presence of a non-conductive material between the first electrode 346 and the second electrode 354. Specifically, the cross-sectional view shows that the first electrode 346 and the second electrode 354 are surrounded on each side by the non-conductive material (excluding the electrode portions exposed along the first surface 344 and the second surface 352). As shown in Figure 3d, the conductive path formed between the first electrode 346 and the second electrode 354 must pass around the first non-conductive portion 360 and the second non-conductive portion 362. This ensures that the conductive path includes tissue adjacent to either the first surface 344 or the second surface 352.

[0027] Referring here to Figures 4a to 4c, top views of several nonconductive sections 470, 474, and 478 are shown. The nonconductive sections 470, 474, and 478 each include recesses 472, 476, and 480 for receiving and holding electrodes. In each of these embodiments, the size of the recesses 472, 476, and 480 is the same. By changing the size of the nonconductive sections, the size of the area to be treated by electroporation can be changed accordingly. A smaller nonconductive section reduces the size of the area to be treated by electroporation. A larger nonconductive section increases the size of the area to be treated by electroporation. Depending on the application, various configurations of electrode assemblies with nonconductive sections of various sizes may be selected to increase or decrease the area to be treated by electroporation. For example, in cardiac ablation type treatments that rely on irreversible electroporation (IRE) treatment, it may be beneficial to use an electrode assembly with larger nonconductive sections (e.g., as shown in Figure 4c) to reduce the time required to ablate the desired tissue. In other embodiments, more targeted cell selection may be required, and smaller diameter non-conductive portions (such as those shown in Figure 4a) may be used.

[0028] In some embodiments, the diameter of the recess 472 configured to receive the electrode is 50% or less of the diameter of the non-conductive portion 470, as shown in Figure 4a. In some embodiments, the diameter of the recess 476 is 33% or less of the diameter of the non-conductive portion 474, as shown in Figure 4b. In some embodiments, the diameter of the recess 480 is 25% or less of the diameter of the non-conductive portion 478, as shown in Figure 4c.

[0029] For example, in some embodiments, the diameter of the non-conductive portion 470 shown in Figure 4a is approximately 6-10 mm, and the diameter of the recess 472 is approximately 3-5 mm. Similarly, the diameter of the non-conductive portion 474 shown in Figure 4b is approximately 10-12 mm, and the diameter of the recess remains approximately 3-5 mm. Similarly, the diameter of the non-conductive portion 478 shown in Figure 4c is approximately 12-14 mm, and the diameter of the recess remains approximately 305 mm.

[0030] Referring to Figure 5, another embodiment of the adaptable electrode assembly 520 is shown according to several embodiments. In the embodiment shown in Figure 5, the adaptable electrode assembly 520 is again positioned at the distal end 516 of the shaft 514 and includes a first surface 544 and a second surface 552 opposite the first surface 544. In some embodiments, the first surface 544 includes a non-conductive portion 548, a first central electrode 546, and a plurality of additional electrodes 584 positioned on the outer edge of the first surface 544. In some embodiments, the first central electrode 546 and the plurality of additional electrodes 584 are fabricated on a flexible circuit board 582 (shown in more detail in Figure 6). Furthermore, in some embodiments, the adaptable electrode assembly 520 may also include one or more ring electrodes 540, 542 positioned on the shaft 514. As described above, in some embodiments, the signals measured by the ring electrodes 540, 542 may be used for localization / navigation purposes. In some embodiments, one of the ring electrodes 540, 542 may be used as a return electrode for the electroporation pulse delivered to the first central electrode 546. In some embodiments, a second central electrode (not shown) may also be located on the second surface 552 of the electrode assembly 520. In some embodiments, the second surface 552 may also include a plurality of additional electrodes located on the outer edge of the second surface 552. In some embodiments, the second surface 552 is symmetrical to the first surface 544. In other embodiments, the second surface 552 may have fewer or more electrodes than the first surface 544, or may not contain any electrodes at all.

[0031] As shown in Figure 5, the first central electrode 546 is surrounded by a non-conductive portion 548. In some embodiments, the non-conductive portion 548 includes a recess for housing the first central electrode 546, and the first central electrode 546 is surrounded by the non-conductive material 548 on all surfaces except the surface that is in contact with the tissue. Here again, the surface area of ​​the first central electrode 546 is smaller than the surface area of ​​the non-conductive portion 548. In some embodiments, the first central electrode 546 and the non-conductive portion 548 are relatively planar along the first surface 544. In some embodiments, the first central electrode 546 is recessed within the non-conductive portion 548, and the non-conductive portion 548 is raised relative to the first central electrode 546. As described above, the purpose of the non-conductive portion 548 surrounding the first central electrode 546 is to ensure that the conductive path formed between the first central electrode 546 and the second electrode (for example, positioned on the second surface 552) during electroporation treatment includes the tissue adjacent to the first central electrode 546. In other words, the non-conductive portion 548 includes the tissue adjacent to the conductive path as desired.

[0032] In some embodiments, the non-conductive portion 548 is also recessed to receive and hold the flexible circuit board 582, the plurality of electrodes 584, and the first central electrode 546. In some embodiments, the non-conductive portion 508 is recessed so that the plurality of electrodes 584 and the first central electrode 546 are relatively planar with the non-conductive portion 548. In other embodiments, the plurality of electrodes 584 may be recessed so that the non-conductive portion 584 is raised or protrudes relative to the plurality of electrodes 584 (as described above with respect to the first central electrode 546). In some embodiments, the plurality of electrodes 584 are not used to deliver electroporation pulses but are used for purposes such as mapping, navigation, and / or visualization, so it may be desirable for the plurality of electrodes 584 to protrude from the non-conductive portion 548. The advantage of the plurality of electrodes 584 protruding from the non-conductive portion 548 is that it is easier to ensure good physical contact with adjacent tissue to sense signals used for one or more of mapping, navigation, and / or visualization.

[0033] Multiple additional electrodes 584 are used to provide one or more additional functions related to the electrode assembly 520. For example, multiple additional electrodes 584 may be used to perform a mapping function, in which case the first surface 544 is positioned in contact with the tissue and electrical signals within the tissue are detected by each of the multiple electrodes 584. The detected electrical signals may be used to detect and map electrical activity within the cardiac tissue, such as abnormal or erroneous electrical signals that result in an arrhythmia. In addition, multiple additional electrodes 584 may be used for visualization and / or navigation of the distal end 516 of the shaft 514 within the patient's body. In some embodiments, the first central electrode 546 may be used in combination with the multiple electrodes 584 to help perform one or more of the mapping, visualization, and / or navigation functions.

[0034] As described above, during electroporation treatment, it is desirable that the first surface 544 (or, if the second surface includes an electroporation electrode, the second surface 552) be positioned in contact with the tissue to be treated, thereby ensuring that the conductive path between the first central electrode 546 and the second electrode includes the tissue adjacent to the first central electrode 546. In some embodiments, a plurality of additional electrodes 584 may be used to detect whether the first surface 544 is in contact with the desired tissue. In some embodiments, contact with tissue is detected based on an electrical signal sensed by one or more of the plurality of additional electrodes 584. For example, sufficient contact of the non-conductive portion 548 surrounding the first central electrode 546 may be determined based on an electrical signal sensed by an electrode 584 in contact with adjacent tissue (i.e., an electrical signal transmitted through cardiac tissue). If an electrode 584 cannot detect an electrical signal, this indicates that the non-conductive portion 548 may not be in contact with the underlying tissue. In other embodiments, one or more other sensing signals may be utilized. For example, the impedance between one or more of the multiple electrodes 584 and the first central electrode 546 (and / or between each other) may be used to determine whether the first surface 544 is in contact with the desired tissue. In some embodiments, the determination of whether the nonconductive portion 548 is in sufficient contact with the underlying tissue is based on a threshold number of electrodes 584 that sense signals indicating physical contact with the underlying tissue. For example, in embodiments in which the multiple electrodes 584 include a total of eight electrodes, the threshold may require that six of the electrodes 584 sense signals indicating contact with the tissue in order to prove that the nonconductive portion 548 is in contact with the underlying tissue.

[0035] In some embodiments, the circuit board 582 is a flexible circuit that allows the circuit board 582 to bend together with the flexible non-conductive portion 548. In some embodiments, the circuit board 582 includes a shape memory material. In some embodiments, the adaptable electrode assembly 520 is made of a flexible material that allows the adaptable electrode assembly 520 to be wound up to fit onto the tube of the shaft 514 during catheter navigation to a desired position in the patient's body. In some embodiments, when the adaptable electrode assembly 520 is removed from the shaft 514, the shape memory material used in the circuit board 582 works to return the adaptable electrode assembly 520 to the desired shape. For example, in the embodiment shown in Figure 5, both the first surface 544 and the second surface 552 extend substantially parallel to each other, and the geometric shape of the adaptable electrode assembly 520 is relatively flat. In other embodiments, the shape memory material allows other shapes to be realized by the electrode assembly 520. For example, the first surface 544 may have a concave shape, a convex shape, or other desired geometric shape.

[0036] Referring to Figures 6a to 6c, an electrode assembly 620 is shown that utilizes the circuit board 682 in combination with the non-conductive part 648. Figure 6a is an isometric view of the electrode assembly 620, Figure 6b is a cross-sectional view of the electrode assembly 620, and Figure 6c is an isometric view of the flexible circuit board 682.

[0037] As shown in Figure 6c, the circuit board 682 includes a first central electrode 646, as well as a plurality of electrodes 684 arranged around the periphery of the circuit board 682. In some embodiments, the circuit board 682 may be attached to a non-conductive portion of the electrode assembly (e.g., a non-conductive portion 548 shown in Figure 5). In other embodiments shown in Figures 6a and 6b, the non-conductive portion 648 is present around (i.e., surrounds) at least a portion of the circuit board 682 and includes a plurality of recesses or openings that expose one or more electrodes associated with the circuit board 682. In the embodiment shown in Figure 6a, the non-conductive portion 648 includes a central recess 645 that exposes the first central electrode 646, and a plurality of peripheral recesses 685, each of which exposes one of a plurality of peripheral electrodes 684. In some embodiments, the first central electrode 646 and the plurality of peripheral electrodes 684 are recessed relative to the plane of the non-conductive portion 648. In other embodiments, one or both of the first central electrode 646 and the plurality of peripheral electrodes 684, together with the non-conductive portion 648, form a substantially flat surface for contact with tissue. In some embodiments, the components and geometric shapes provided on the first surface 644 of the electrode assembly 620 are very similar on the second surface 652 of the electrode assembly 620. In other embodiments, the second surface 652 may not contain electrodes (and therefore may not have recesses in the non-conductive portion 648), or it may contain only a subset of the electrodes and recesses included in the first surface 644.

[0038] The cross-sectional view shown in Figure 6b shows layers not visible in the diagram shown in Figure 6a. For example, in the embodiment shown in Figure 6b, the intermediate layer 692 is positioned adjacent to the circuit board 682. In some embodiments, the intermediate layer 692 is located between the first circuit board 682 (including electrodes 646 and 684 associated with the first face 644) and the second circuit board 694 associated with electrodes (not indicated) positioned on the second face 652. In some embodiments, the intermediate layer 692 includes a shape memory material such as nitinol (i.e., nickel-titanium). In some embodiments, the shape memory material of the intermediate layer 692 allows the intermediate layer to be deformable (e.g., rolled up to fit onto a catheter tube) and then returned to the substantially planar shape shown in Figures 6a-6b. By combining the flexible circuit boards 682, 694 with the flexible non-conductive portion 648, the electrode assembly 620 may be deformed to fit onto a catheter tube while navigating the electrode assembly 620 to the desired location. When the electrode assembly 620 is unfolded from the tube, the shape memory material (whether included as part of the intermediate layer 692 or in other parts) can return to its original shape, such as the planar shape shown in Figures 6a-6b, or a predetermined shape. In some embodiments, the circuit boards 682 and / or 694 are made of shape memory material, either in conjunction with or instead of the intermediate layer 692 being made of shape memory material, with the first circuit board 682 and / or the second circuit board 694 being made of shape memory material. In the examples shown in Figures 6a-6c, the predetermined configuration or shape of the electrode assembly is relatively flat. However, in other embodiments, this shape or configuration may include a number of possible geometric shapes, such as concave shapes or composite shapes.

[0039] Figure 6c shows the circuit board 682 separated from the non-conductive portion 648. In some embodiments, the circuit board 682 includes a proximal portion 690 extending into the tube of the shaft, the proximal portion 690 including a plurality of contact pads 686 for providing contact to a plurality of electrodes 684 arranged on the outer circumference of the circuit board 682, and a contact pad 687 for providing contact to a first central electrode 646. The circuit board 682 further includes a distal portion 689 and a ring portion 688 extending from the proximal portion 690. In particular, the ring portion 688 forms a ring around the distal portion 689. In some embodiments, the distal portion 689 extends across the diameter of the ring portion 688. The first central electrode 646 is mounted or fabricated on the distal portion 689. The plurality of electrodes 684 are equidistant along the ring portion 688. Each of the electrodes 684 is connected to one of the plurality of contact pads 686 via a conductive trace. Similarly, the first central electrode 646 is connected to the contact pad 687 via a conductive trace.

[0040] In some embodiments, the circuit board 682 may have a multilayer structure (not shown in Figure 6c). For example, in some embodiments, the circuit board 682 includes an upper and lower surface, with at least some of the conductive traces formed between the contact pads 686 and the electrodes 684 located on the upper surface and some of the conductive traces formed on the lower surface. For example, the embodiment shown in Figure 6a shows a subset of conductive traces extending along the upper surface of the circuit board 682.

[0041] Referring now to Figures 7a and 7b, side and top views of the shaft 714 and electrode assembly 720 are shown, respectively, according to several embodiments. In Figure 7a, the electrode assembly 720 is oriented so that the first surface 744 and the second surface 752 of the electrode assembly are not visible. In Figure 7b, a top view of the shaft 714 and electrode assembly 720 is shown, with the first central electrode 746 and additional electrodes 784 positioned on the outer edge of the electrode assembly 720 visible.

[0042] Figure 8 is a flowchart of steps used to provide electroporation therapy in several embodiments. In step 800, a catheter shaft including a compatible electrode assembly is introduced into the patient's body and moved to a target location. In some embodiments, one or more sensors including one or more electrodes placed on the compatible electrode assembly may be used to help navigate and / or visualize the position of the catheter within the patient's body.

[0043] In step 802, one or more physiological signals are measured using one or more electrodes positioned on the first face of a compatible electrode assembly. In some embodiments, the compatible electrode assembly includes a plurality of electrodes positioned on the outer edge of the first face, each of which may be used to sense one or more electrical signals. For example, the sensed signal may include an electrical signal sensed within myocardial tissue. In other embodiments, the sensed signal may include an impedance signal measured between two or more electrodes. In other embodiments, one or more signals or combinations of signals may be measured. In some embodiments, a first central electrode used to deliver electroporation therapy may also be used to measure one or more physiological signals.

[0044] In step 804, tissue contact is detected based on one or more signals measured in step 802. It is desirable to ensure that the first surface (including the first electroporation electrode) is in contact with the tissue to be treated before applying electroporation therapy (including irreversible electroporation (IRE)). In some embodiments, it is desirable that the non-conductive portion surrounding the first electroporation electrode is also in good contact with the tissue in order to ensure that a conductive path is formed between the electroporation electrodes, including the tissue adjacent to the first electroporation electrode. In some embodiments, the determination is made based only on the signal measured by the first central electrode. In other embodiments, the determination is made based on the signal detected using one or more of the multiple electrodes (if any) arranged on the outer edge of the first surface (as shown, for example, in Figures 5 and 6). In some embodiments, sufficient tissue contact is detected when a threshold number of electrodes detect signals indicating tissue contact. For example, in some embodiments, sufficient tissue contact is detected when six of the eight electrodes arranged on the outer edge of the first surface detect contact with adjacent tissue. In other embodiments, other thresholds based on available sensors may be used to determine whether the first surface is in contact with an adjacent tissue.

[0045] If no tissue contact is detected in step 804, the electrode assembly is repositioned in step 806, and the process is repeated in step 802 by measuring one or more physiological signals using one or more of the electrodes. If tissue contact is detected in step 804, the electroporation treatment is initiated in step 808. In some embodiments, the electroporation treatment may include irreversible electroporation (IRE). In some embodiments, the electroporation treatment includes a series of pulse deliveries between a pair of electrodes, i.e., between a cathode and an anode, with one of the electrodes positioned on a first surface of the electrode assembly adjacent to the tissue.

[0046] In some embodiments, in step 810, one or more physiological signals are measured by one or more of a plurality of electrodes arranged on the first surface (in some embodiments, including one or more of an electroporation electrode and / or a plurality of electrodes arranged on the outer edge of the first surface). In some embodiments, the measured physiological signals are used to determine the effectiveness of the electroporation treatment delivered to the tissue. For example, in some embodiments, this may include monitoring electrical signals within the tissue to determine whether the electroporation has successfully blocked the propagation of these signals through the electroporated tissue.

[0047] In step 812, a determination is made as to whether the electroporation treatment was successful based on one or more physiological signals measured in step 810. If one or more physiological signals indicate that the electroporation treatment was successful, the process ends (or the catheter is moved to a new location and the process is repeated). If one or more physiological signals indicate that the electroporation treatment was unsuccessful (for example, if electrical signals propagating through the electroporated tissue are detected), the process is repeated from step 802, in which one or more physiological signals are measured to determine whether the first surface of the electrode assembly is in good contact with the tissue being treated.

[0048] While the present invention has been described with reference to exemplary embodiments, those skilled in the art will understand that various modifications can be made and equivalents can be used in place of elements without departing from the scope of the invention. In addition, many modifications can be made to adapt the teachings of the invention to specific situations or materials without departing from the essential scope of the invention. Thus, the present invention is not limited to the specific embodiments disclosed, and is intended to include all embodiments that fall within the scope of the appended claims.

[0049] Discussion of the disclosed embodiments The following is a non-exclusive description of possible embodiments of the present invention.

[0050] According to one embodiment, the electroporation device includes a shaft having a proximal end and a distal end, and a adaptable electrode assembly located at the distal end of the shaft. The electrode assembly includes a first surface and a second surface, the first surface including a first nonconductive portion and a first electrode located in the center of the first surface, the first nonconductive portion being defined by a first surface area, and the first electrode being defined by a second surface area, the first surface area being greater than the second surface area.

[0051] The devices described in the preceding paragraph may optionally include, in addition and / or alternatively, any one or more of the following features, configurations, and / or additional components:

[0052] For example, in some embodiments, the first electrode and the first nonconductive portion may form a relatively flat surface for contact with the tissue.

[0053] In some embodiments, the first electrode may be recessed within the first nonconductive portion, and the first nonconductive portion may be positioned higher than the first electrode.

[0054] In some embodiments, the first electrode may be mounted in a recess provided in the first nonconductive portion, and the first electrode may be positioned higher than the first nonconductive portion.

[0055] In some embodiments, the first nonconductive portion may be flexible.

[0056] In some embodiments, the device may further include a second electrode, the first and second electrodes configured to deliver electroporation therapy to tissue adjacent to the first surface of the electrode assembly.

[0057] In some embodiments, the second electrode may be positioned on the second surface of a compatible electrode assembly that faces the first surface.

[0058] In some embodiments, the second surface may include a second nonconductive portion, and the second electrode may be attached to the second nonconductive portion and positioned in the center of the second surface, the second nonconductive portion may be defined by a third surface area, and the second electrode may be defined by a fourth surface area, the third surface area being larger than the fourth surface area.

[0059] In some embodiments, the second electrode may be a ring electrode positioned on the shaft.

[0060] In some embodiments, the device may further include a circuit board, the first electrode may be mounted on the circuit board, and the non-conductive portion may surround the circuit board.

[0061] In some embodiments, the non-conductive portion may include an opening aligned with the first electrode, and the first electrode may be recessed relative to the non-conductive portion.

[0062] In some embodiments, the circuit board may be a flexible circuit board including a shape memory layer, the shape memory layer having a predetermined geometric shape.

[0063] In some embodiments, the predefined geometric shape may be one of a convex shape, a concave shape, or a planar shape.

[0064] In some embodiments, the first set of peripheral electrodes may be positioned on the outer edge of the first surface of the compatible electrode assembly.

[0065] In another embodiment, a method for delivering electroporation therapy includes the step of introducing a catheter shaft having a compatible electrode assembly to a target site in a patient. The method may further include the step of positioning a first surface of the compatible electrode assembly in contact with the target tissue, the first surface of the compatible electrode assembly may include a first nonconductive portion and a first electrode located in the center of the first surface, the first nonconductive portion surrounding the first electrode. The method may further include the step of delivering electroporation pulses to the first electrode.

[0066] The method described in the preceding paragraph may optionally include, in addition and / or alternatively, one or more of the following steps:

[0067] For example, in some embodiments, the method may further include the step of measuring one or more signals using one or more of a first plurality of peripheral electrodes positioned on a first surface of a adaptable electrode assembly. The method may further include the step of determining, based on one or more measured signals, whether the first surface of the adaptable electrode assembly is in contact with tissue, and, in response to the determination that the adaptable electrode assembly is not in contact with tissue, the step of repositioning the adaptable electrode assembly.

[0068] In some embodiments, the step of measuring one or more signals may include measuring one or more of the electrical activity within the tissue and the impedance between one or more of a plurality of peripheral electrodes.

[0069] In some embodiments, the method may further include the step of measuring one or more signals using one or more of a first plurality of peripheral electrodes arranged on a first face of a compatible electrode assembly. The method may further include the step of determining, based on one or more measured signals, whether the delivered electroporation treatment was effective, and, in response to the determination that the delivered electroporation treatment was ineffective, rearranging the compatible electrode assembly and delivering the next electroporation treatment.

[0070] In another embodiment, the electroporation treatment system may include a catheter and an electroporation generator. The catheter may further include a handle, a compatible electrode assembly, and a shaft coupled to the handle at its proximal end and to the electrode assembly at its distal end. The compatible electrode assembly may include a first surface and a second surface opposite to the first surface, the first surface including a first nonconductive portion and a first electrode attached to the first nonconductive portion, the first electrode being centrally positioned and the nonconductive portion surrounding the first electrode in a plane defined by the first surface. The electroporation generator may be coupled to the catheter to deliver electroporation pulses to the first electrode.

[0071] The electroporation treatment system described in the preceding paragraph may optionally include, in addition to and / or alternatively, any one or more of the following features, configurations, and / or additional components:

[0072] For example, in some embodiments, the adaptable electrode assembly may further include a plurality of first peripheral electrodes positioned on the outer edge of the first surface of the adaptable electrode assembly.

[0073] In some embodiments, the first electrode and a first plurality of electrodes may be arranged on a shape-memory flexible substrate having a predetermined geometric shape, and the compatible electrode assembly is configured to fit into a shaft tube.

Claims

1. Electroporation device, A shaft having a proximal end and a distal end, An electrode assembly positioned at the distal end of the shaft, Equipped with, The electrode assembly is The first side, A second surface located on the opposite side of the first surface and parallel to the first surface, It has an outer surface located around the first surface and the second surface, The outer surface is connected to the distal end, The first surface includes a first electrode positioned in the center of the first surface, a non-conductive portion surrounding the first electrode, and a plurality of peripheral electrodes positioned on the outer edge of the first surface. Electroporation device.

2. The electroporation device according to claim 1, wherein the first electrode and the non-conductive portion form a relatively flat surface for contact with tissue.

3. The first electrode is recessed within the non-conductive portion. The electroporation device according to claim 1, wherein the non-conductive portion is positioned higher than the first electrode.

4. The electroporation device according to claim 1, wherein the non-conductive portion is flexible.

5. The first electrode and the plurality of peripheral electrodes are arranged on a shape-memory flexible substrate having a predetermined geometric shape. The electroporation device according to claim 1, wherein the electrode assembly is configured to fit into the tube of the shaft.

6. The electroporation device according to claim 1, wherein the second surface includes a second electrode.

7. Further comprising a plurality of additional electrodes, The second electrode is positioned in the center of the second surface, The electroporation device according to claim 6, wherein the plurality of additional electrodes are arranged on the outer edge of the second surface.

8. The electroporation device according to claim 7, wherein the second surface is symmetrical to the first surface.

9. The electroporation device according to claim 1, wherein the second surface has fewer electrodes than the first surface.

10. The electroporation device according to claim 1, wherein the second surface has more electrodes than the first surface.

11. The electroporation device according to claim 1, wherein the second surface has no electrodes.

12. The electroporation device according to claim 1, wherein the plurality of peripheral electrodes protrude from the nonconductive portion and are arranged on the outer edge of the first surface.

13. The electroporation device according to claim 1, further comprising one or more ring electrodes arranged on the shaft.

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