Virtually short-circuited electrodes for an IRE pulse generator

Abstract

To provide a medical apparatus.SOLUTION: The medical apparatus includes a probe, which includes an insertion tube configured for insertion into a body cavity of a patient, and a distal assembly, which is connected distally to the insertion tube and comprises a plurality of electrodes, which are configured to contact tissue within the body cavity. An electrical signal generator is configured to apply biphasic electrical pulses simultaneously to at least one group of two or more of the electrodes, with energy sufficient to irreversibly electroporate the tissue contacted by the electrodes in the at least one group. A controller is coupled to measure time-varying voltage differences between the electrodes in the at least one group and to adjust the biphasic electrical pulses applied to the electrodes in the at least one group so that the voltage differences do not exceed a predetermined threshold at any time during the application of the biphasic electrical pulses.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention broadly relates to medical devices, and more particularly to devices and methods for irreversible electroporation of biological tissue.

Background Art

[0002] Irreversible electroporation (IRE) is a soft tissue ablation technique that applies short pulses of a strong electric field to form permanent, and thus lethal, nanopores in cell membranes, thereby disrupting cell homeostasis (internal physical and chemical conditions). Cell death after IRE is due to apoptosis (programmed cell death) and not necrosis (cell injury that results in the destruction of cells through the action of enzymes within the cells themselves) as in all other heat or radiation-based ablation techniques. IRE is commonly used for ablation of tumors in areas where precision and preservation of the extracellular matrix, blood flow, and nerves are important.

[0003] U.S. Patent Application Publication No. 2010 / 0125315 describes a method and system for providing treatment to a patient in which an array of electrodes is implanted. An electrical stimulation current is transmitted from at least two of the electrodes along at least two electrical paths through the patient's tissue to at least one of the electrodes, and the electrical stimulation current is shifted between the electrical paths by actively adjusting one or more finite resistances each associated with one or more of the electrical paths.

Summary of the Invention

Means for Solving the Problems

[0004] Embodiments of the present invention described below provide improved devices and methods for irreversible electroporation of body tissue.

[0005] Accordingly, according to one embodiment of the present invention, there is provided a medical device including a probe including an insertion tube configured for insertion into a patient's body cavity, a plurality of electrodes configured to contact tissue within the body cavity, and a distal assembly connected to the distal side of the insertion tube. An electrical signal generator is configured to apply a biphasic electrical pulse simultaneously to at least one group consisting of two or more of the electrodes with sufficient energy to irreversibly electroporate tissue contacting the electrodes within the at least one group. A controller is coupled to measure a time-varying voltage difference between the electrodes within the at least one group and to adjust the biphasic electrical pulse applied to the electrodes within the at least one group such that the voltage difference does not exceed a predetermined threshold at any point during the application of the biphasic electrical pulse.

[0006] In some embodiments, the controller is configured to adjust the amplitude of the biphasic electrical pulse to compensate for the difference in the respective peak voltages measured across any pair of electrodes within the at least one group of electrodes. In one embodiment, the controller is configured to adjust the phase of the biphasic electrical pulse to compensate for the phase offset between the respective voltage waveforms measured across any pair of electrodes within the at least one group of electrodes.

[0007] In a further embodiment, the distal assembly includes a balloon configured to be connected to the distal side of the insertion tube and to be inflated within the body cavity by fluid flowing through the insertion tube to the balloon.

[0008] In a further embodiment, the device includes a common electrode configured to be fixed to a location on the patient's body, and the biphasic electrical pulse irreversibly electroporates tissue in monopolar mode by passing through the body from the plurality of electrodes to the common electrode.

[0009] In yet a further embodiment, at least one group includes a first group and a second group, and the biphasic electrical pulse is applied in bipolar mode between the electrodes of the first group and the electrodes of the second group, and the controller measures the time-varying voltage difference between the electrodes of the first group and the electrodes of the second group and is coupled to adjust the biphasic electrical pulse applied to the electrodes of the first group and the electrodes of the second group such that the voltage difference between the electrodes of the first group and the electrodes of the second group includes a predetermined train of biphasic electrical pulses.

[0010] Furthermore, according to one embodiment of the present invention, a method for a medical treatment is also provided. The method includes providing a probe for insertion into a patient's body cavity, the probe including an insertion tube and a plurality of electrodes configured to contact tissue within the body cavity, and a distal assembly connected to the distal side of the insertion tube. A biphasic electrical pulse is applied simultaneously to at least one group consisting of two or more of the electrodes with sufficient energy to irreversibly electroporate the tissue contacting the electrodes within the at least one group. A time-varying voltage difference is measured between the electrodes within the at least one group, and the biphasic electrical pulse applied to the electrodes within the at least one group is adjusted such that the voltage difference does not exceed a predetermined threshold at any point during the application of the biphasic electrical pulse.

Brief Description of the Drawings

[0011] The present invention will be more fully understood by considering the following "Detailed Description of the Invention" in conjunction with the drawings.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

[0012] Overview IRE is a mainly non-thermal ablation process that raises the temperature of tissue by only a few degrees over a maximum of a few milliseconds. Thus, IRE is different from RF (radio frequency) ablation, which raises tissue temperature by 20 - 70 °C and destroys cells by heating. IRE uses biphasic pulses (a combination of positive and negative pulses) to avoid muscle contractions due to a non-zero DC voltage component. Biphasic pulses are generally also referred to as "bipolar" pulses. However, as will be explained in more detail below, IRE may be performed in either monopolar or bipolar mode. To avoid confusion, the term "bipolar" is used below only in the context of the bipolar mode of IRE.

[0013] Some IRE procedures use a balloon catheter having a balloon located at the distal end and electrodes arranged on the surface of the balloon. The balloon is inflated within a body cavity and the electrodes are brought into contact with the tissue to be electroporated. A small-diameter balloon having a diameter of less than, for example, 15 mm can be used to electroporate tissue in a small cavity within the body, such as the tissue of the left atrium of the heart.

[0014] IRE can be performed in either a bipolar mode where the electroporation current flows from one electroporation electrode to another on the same catheter, or a monopolar mode where the electroporation current flows between an electroporation electrode on the catheter and an external electrode referred to as a "return patch". The return patch is typically fixed to the subject's body surface, such as on the skin of the subject's torso, while providing an electrical return connection to the IRE signal generator.

[0015] Electrodes arranged on a small-diameter balloon, as well as electrodes arranged on other types of electrode assemblies used in IRE procedures, are generally small in size to enable precise targeting of ablation energy. Typically, an electrical signal generator (also referred to herein as an "IRE pulse generator") that applies IRE pulses to the electrodes enables individual operation of each electrode via a respective channel of the generator. Since each electrode is small in size, it contacts and ablates only a small area of tissue.

[0016] In some cases, it may be desirable to apply IRE over an area of tissue larger than the area that can be covered by a single small electrode. For this purpose, a larger effective electroporation area can be created by grouping two or more adjacent electrodes together by electrically shorting them to each other. However, implementing this approach in hardware requires additional high-voltage switches between the individual output channels of the IRE pulse generator. These additional switches are expensive, require dedicated control lines, and have limited flexibility in generating different groupings of electrodes.

[0017] Embodiments of the invention described herein address this problem by enabling a “virtual short circuit” of a group of two or more electrodes within an IRE system. The electrodes are “virtually shorted” in the sense that all the electrodes within the group apply the same voltage waveform having the same amplitude and phase simultaneously to the tissue with which they are in contact. Thus, the IRE current flows through a larger region of tissue defined by the contact locations of all the electrodes within the group.

[0018] However, this type of virtual short circuit cannot be reliably achieved simply by setting the IRE pulse generator to apply the same waveform to all the electrodes within the group. For example, local differences in tissue impedance, as well as differences in contact impedance between the electrodes within the group and the tissue with which they are in contact, can cause variations in the amplitude and phase of the IRE waveform actually applied to the tissue by the various electrodes. This non-uniformity of the waveform can cause the IRE current to flow through the tissue along an unexpected path, resulting in unsatisfactory ablation results.

[0019] Embodiments of the invention described herein address this problem by measuring the time-varying voltage difference between the electrodes within the group. Based on these measurements, the IRE pulse generator adjusts the biphasic electrical pulse applied to the electrodes within the group so that the voltage difference does not exceed a predetermined threshold at any point during the application of the biphasic electrical pulse.

[0020] In the disclosed embodiments, in a monopolar IRE treatment, the IRE pulse generator applies a biphasic IRE pulse simultaneously to a selected group of electrodes on the probe with sufficient energy to electroporate the tissue in contact with the electrodes. The controller measures the time-varying voltage difference between the electrodes within the group and adjusts the amplitude and phase of the IRE pulse so that the voltage difference does not exceed a predetermined threshold at any point during the application of the IRE pulse. This technique ensures that the group of electrodes applies the IRE pulse as if the group were a single large-area electrode.

[0021] In bipolar IRE treatment, the IRE pulse needs to flow through the tissue from one group of electrodes to another group of electrodes. For this purpose, the controller adjusts the relative amplitude and phase between the IRE pulses applied to the two groups to generate a series of IRE pulses between the two groups for bipolar electroporation in the tissue between these two groups of electrodes. In addition, similar to monopolar IRE, the controller adjusts the amplitude and phase of the IRE pulses within each group so that the voltage difference between the electrodes of the group does not exceed a predetermined threshold at any point during the application of the IRE pulse.

[0022] Description of the System FIG. 1 is a schematic drawing of a medical device 20 during an IRE treatment according to an embodiment of the present invention. A physician 22 performs an IRE treatment on a patient 24 using an electroporation catheter 26 (further details of the catheter are described below). The embodiment shown in the figure relates to an example of an IRE treatment within the ventricle of the heart 27 using a balloon 32. In another embodiment, the IRE treatment may be performed using other types of catheters having multiple electrodes, and as will be apparent to those skilled in the art upon reviewing this specification, it can be performed not only on the heart 27 but also on other organs and tissues.

[0023] As shown in the inset FIG. 36, the electroporation catheter 26 includes a shaft 28 and a distal assembly 30. The shaft functions as an insertion tube for inserting the distal assembly into the body cavity of the patient 24, in this case into the ventricle of the heart 27. The distal assembly 30 includes a balloon 32 having a plurality of electroporation electrodes 34. A portion of the distal assembly 30 and the shaft 28 are also shown in the inset FIG. 38. In an alternative embodiment, the distal assembly 30 may have a structure different from the balloon.

[0024] The medical device 20 further includes a controller 42 and an electrical signal generator configured as an IRE pulse generator 44, typically present within the console 46. The controller and the signal generator can each include one or more circuit components. Further details of this type of signal generator are described in U.S. Patent Application No. 16 / 701,989, filed December 3, 2019, and U.S. Patent Application No. 17 / 092,662, filed November 9, 2020, both of which disclosures are hereby incorporated herein by reference. The catheter 26 is connected to the console 46 via an electrical interface 48 that conveys IRE pulses, such as ports or sockets, from the IRE pulse generator 44 to the distal assembly 30. The console 40 includes an input device 49, such as a keyboard and mouse, and a display screen 58.

[0025] The controller 42 receives, from the physician 22 (or other operator), setting parameters 51 for the procedure before and / or during the electroporation procedure. For example, using one or more suitable input devices, such as a keyboard, mouse, or touch screen (not shown), the physician 22 determines the electrical and temporal parameters of the IRE pulses applied to the selected electrodes 34. The controller 42 passes appropriate control signals to the IRE pulse generator 44 to effect the IRE.

[0026] The controller 42 can be further configured to track the respective positions of the electrodes 34 during the IRE procedure using any suitable tracking technique. For example, the distal assembly 30 can include one or more electromagnetic position sensors (not shown) that output a signal that varies according to the position of the sensor in the presence of an external magnetic field generated by one or more magnetic field generators 50. Based on these signals, the controller 42 can confirm the positions of the electrodes 34. The magnetic field generator 50 is connected to the console 46 via a cable 52 and an interface 54. Alternatively, for each electrode 34, the controller 42 can confirm the respective impedance between the electrode and a plurality of external electrodes 56 that are coupled to the patient 24 at various different positions and are connected to the console 46 by a cable 39. The controller 42 calculates the ratio between these impedances, and these ratios represent the positions of the respective electrodes 34. As yet another alternative, the controller may use both electromagnetic tracking and impedance-based tracking, as described, for example, in U.S. Patent No. 8,456,182, the disclosure of which is incorporated herein by reference.

[0027] In some embodiments, the controller 42 annotates and displays on the display screen 58 an image 60 of the subject's body structure in relation to, for example, the current position and orientation of the distal assembly 30.

[0028] The controller 42 and the electrical IRE pulse generator 44 can typically include both analog and digital elements. Accordingly, the controller 42 includes an analog front end having a plurality of inputs each with an analog-to-digital converter (ADC) for monitoring the IRE pulses applied to each electrode 34 by the IRE pulse generator 44. The controller 42 further includes a plurality of digital output circuits for sending commands to the IRE pulse generator 44 to adjust the IRE pulses, as will be detailed below with reference to FIGS. 4-6.

[0029] The electrical IRE pulse generator 44 typically comprises an analog circuit for generating and amplifying the IRE pulses for electroporation, and a digital input circuit for receiving digital control signals from the controller 42.

[0030] Alternatively, it is also possible to transmit the control signal from the controller 42 to the electrical IRE pulse generator 44 in analog form, provided that the controller and the IRE pulse generator are configured accordingly.

[0031] Typically, the functions of the controller 42 are at least partially realized in software, as described herein. For example, the controller 42 can comprise a programmed digital computing device comprising at least a central processing unit (CPU) and a random access memory (RAM). Program code, including software programs, and / or data are loaded into the RAM for execution and processing by the CPU. The program code and / or data can be downloaded in electronic form to the processor, for example, via a network. Alternatively or additionally, the program code and / or data may be provided and / or stored on a non-transitory tangible medium such as magnetic, optical, or electronic memory. Such program code and / or data, when brought to the controller, give rise to a machine or a dedicated computer configured to perform the tasks described herein.

[0032] At the start of the IRE treatment, physician 22 inserts the catheter 26 through the sheath 62 with the balloon 32 in the folded state, and inflates the balloon to the intended functional shape with the fluid flowing into the balloon through the shaft 28 only after the catheter exits the sheath. This functional shape is shown in insertion views 36 and 38. By accommodating the folded balloon 32, the sheath 62 also serves to minimize trauma to the blood vessel when the balloon is brought to the target position. Physician 22 guides the catheter 26 to the target position within the heart 27 of patient 24 by manipulating the catheter using the deflections from the manipulator 64 near the proximal end of the catheter and / or the sheath 62. Physician 22 contacts the distal assembly 30 to tissue such as the myocardial tissue of the heart 27. Next, under the control of physician 22 and the controller 42, the IRE pulse generator 44 generates IRE pulses that are carried through different respective channels through the catheter 26 to the electroporation electrodes 34.

[0033] In the monopolar mode of IRE, the electroporation current flows from one or more electroporation electrodes 34 to an external electrode, or typically to a "return patch" 66 coupled externally between the patient 24 and the IRE pulse generator 44 on the conductor skin of the subject. A catheter 26 having a balloon 32 with a diameter of less than 15 mm is often used to electroporate tissue within a small cavity in the body, such as the left atrium of the heart 27. Due to the small size of the electroporation electrodes 34 of these small-diameter balloons, if an IRE pulse is applied to only one of the electrodes, the area where electroporation occurs may be too small. By short-circuiting and grouping several electrodes 34, a substantially larger electroporation area is considered to occur. This can be achieved by adding a short-circuit switch between the individual output channels of the IRE pulse generator 44, but such an addition is expensive. In an embodiment of the present disclosure, at least two electrodes 34 are grouped together and substantially short-circuited by adjusting the amplitude and phase of the IRE pulses at each of these electrodes to be the same. For this purpose, the controller 42 monitors the amplitude and phase of the IRE pulses at each of the electrodes 34 within the group and transmits a control signal to the IRE pulse generator 44 to equalize these amplitudes and phases.

[0034] In the bipolar mode of IRE, the electroporation current flows between two electrodes or two groups of electrodes 34, and a train of IRE pulses between the electrodes is required. In an embodiment of the present disclosure, the controller 42 monitors the amplitude and phase of the IRE pulses at each of the electrodes 34, as in the monopolar IRE embodiment described above, but here adjusts them to generate the required train of IRE pulses between two electrodes or two groups of electrodes. Further, the controller 42 equalizes the amplitude and phase of the IRE pulses within each group, similar to monopolar IRE.

[0035] Further details of the IRE pulse generator 44 and the controller 42 are shown in FIGS. 4 - 6 below.

[0036] Regardless of the particular type of electroporation treatment shown in FIG. 1, it should be noted that the embodiments described herein are applicable to any suitable type of multi-channel IRE treatment.

[0037] FIG. 2 is a schematic diagram of a biphasic IRE pulse 100 according to an embodiment of the present invention.

[0038] Curve 102 shows the voltage V of the biphasic IRE pulse 100 as a function of time t in the IRE treatment. The biphasic IRE pulse includes a positive pulse 104 and a negative pulse 106, where the terms "positive" and "negative" refer to the arbitrarily selected polarities of the two electrodes to which the biphasic pulse is applied. In monopolar IRE, the biphasic pulse can be applied either between a single electrode 34 and a return patch 66 or between a group of electrodes 34 and the return patch 66. In the case of bipolar IRE, the biphasic pulse can be applied between two electrodes 34 or between two groups of electrodes 34. The amplitude of the positive pulse 104 is labeled V+, and the time width of the pulse is labeled t+. Similarly, the amplitude of the negative pulse 106 is labeled V-, and the time width of the pulse is labeled t-. The time width between the positive pulse 104 and the negative pulse 106 is labeled t 間隔 and labeled. Typical values of the parameters of the biphasic pulse 100 are shown in Table 1 below.

[0039] FIG. 3 is a schematic diagram of a burst 200 of biphasic pulses according to an embodiment of the present invention.

[0040] In the IRE treatment, the IRE signal is provided to the electrodes 34 as one or more bursts 200 shown by curve 202. The burst 200 includes N T pulse trains 204, each train including N P biphasic pulses 100. The length of the pulse train 204 is labeled t T and labeled. The period of the biphasic pulses 100 within the pulse train 204 is labeled t PP and marked, and the interval between consecutive trains is Δ TIt is marked as "___" and no signal is applied during this period. Typical values of the parameters of the burst 200 are shown in Table 1 below.

[0041]

Table 1

[0042] FIG. 4 is a block diagram schematically showing details of a system 20 (FIG. 1) including connections between an IRE pulse generator 44, a controller 42, an electrode 34, and a return patch 66 according to an embodiment of the present invention.

[0043] The IRE pulse generator 44 bounded by the dotted frame 404 includes a pulse generation assembly 406 and a pulse routing and measurement assembly 408, and the routing and measurement assembly will be described in more detail below in FIGS. 5 and 6.

[0044] The controller 42 receives digital voltage and current signals 412 from the pulse routing and measurement assembly 408, communicates a digital command signal 418 derived from the setting parameter 51 to the pulse generation assembly 406, and commands the IRE pulse generator 44 to generate IRE pulses such as the IRE pulses shown in FIGS. 2 and 3 above. These IRE pulses are transmitted as analog pulse signals 420 to the pulse routing and measurement assembly 408. The pulse routing and measurement assembly 408 is coupled to the electrode 34 via an output channel 422 and to the return patch 66 via a connection 424. FIG. 4 shows ten output channels 422 marked as CH1 to CH10. In the following description, each electrode 34 is referred to by the name of the individual channel to which it is coupled. For example, electrode CH5 refers to the electrode coupled to CH5 of the channel 422. Although FIG. 4 shows ten channels 422, instead, the IRE pulse generator 44 may include a different number of channels, such as, for example, eight, sixteen, or twenty channels, or any other suitable number of channels.

[0045] Figure 5 is an electrical schematic diagram of the pulse routing and measurement assembly 408 of FIG. 4 according to an embodiment of the present invention. For clarity, circuits involved in measuring current and voltage are omitted. These circuits are detailed in FIG. 6 below. Output channels 422 and connections 424 are shown in FIG. 5 using the same markings as in FIG. 4.

[0046] The pulse routing and measurement assembly 408 includes a module 502 having one module for each output channel 422. A pair 504 of adjacent modules 502 configured for bipolar IRE is shown in detail in FIG. 6 below. In an alternative, the BP line 506 connected to the return patch 66 can be used as the return path for a unipolar IRE. The module 502 receives a pulse input via respective transformer secondaries 508, 510 driven by a primary coil in the pulse generation assembly 406.

[0047] Each module 502 comprises switches and relays marked FO i , SO i , N i , and BP i . All of the switches FO i are high-speed switches for switching IRE ablation from channel to channel, controlled by a field programmable gate array (FPGA, not shown in the figure), while the switches SO i , N i , and BP i are slower relays used to configure the pulse routing and measurement assembly 408 to a given mode of IRE ablation. The typical switching time of the high-speed switch FO i is less than 0.3 μs, while the slower relays SO i , N i , and BP i require a switching time of only 3 ms.

[0048] Figure 6 is an electrical schematic of two adjacent modules 601 and 602 of the pulse routing and measurement assembly 408 configured according to the IRE in bipolar mode according to an embodiment of the present invention. The use of module 601 for the unipolar mode will be further described below.

[0049] Modules 601 and 602 are configured to represent the pair 504 of FIG. 5 by a dashed frame with the same label (504). Modules 601 and 602 are each supplied by a pulse generation circuit 603 and a pulse generation circuit 604 that include a part of the pulse generation assembly 406 with respect to FIG. 4. Then, modules 601 and 602 supply channels CH1 and CH2, respectively, in the same manner as module 502 of pair 504 in FIG. 5. In FIG. 6, two modules 601 and 602 are shown to indicate the connection 605 between the modules. Since the two modules are identical (and identical to additional modules within the pulse routing and measurement assembly 408), only module 601 will be described in detail below.

[0050] The pulse generation assembly 406 includes one pulse generation circuit similar to circuits 603 and 604 for each channel of the IRE pulse generator 44. The pulse generation circuit 603 is coupled to the module 601 by a transformer 606. High-speed switch FO 1 , as well as low-speed relay SO 1 , N 1 , and BP 1 are labeled in the same manner as in FIG. 5.

[0051] The voltage V 1 and current I 1 coupled to CH1 are shown in FIG. 6 as the voltage between channels CH1 and CH2 and the current flowing into CH1 and returning from CH2.

[0052] V 1 and I 1is measured by a measurement module 612 that includes an operational amplifier 614 for measuring voltage and a differential amplifier 616 for measuring the current across a current sensing resistor 618. The voltage V 1 is measured from a voltage divider 620 that includes resistors R 1 、R 2 、and R 3 、as well as an analog multiplexer 622. The analog multiplexer 622 couples to either resistor R 1 / R 3 or R 2 / R 3 such that the voltage division ratio of the voltage divider 620 is either one of them. The measurement module 612 further includes an analog-to-digital converter (ADC) 624 for converting the measured analog voltages V 1 or R 2 and current I 1 into digital signals DV 1 and DI 1 1 . These digital signals are transmitted as signal 412 (FIG. 4) to the controller 42 via a digital isolator 626. The controller 42 generates a command signal 418 that is transmitted to the pulse generation assembly 406 to adjust the amplitude and phase of the IRE pulses coupled to channels CH1 and CH2 using the received digital signal 412.

[0053] For the purpose of "virtual short circuit", the controller 42 receives signal 412 from each module 502. As an example of the IRE of a diode having "virtually short-circuited electrodes", electrodes CH1, CH2, and CH3 (coupled to channels CH1, CH2, and CH3) are selected as one of the enlarged electrodes, and electrodes CH4, CH5, and CH6 are selected as the other enlarged electrode. Signals from electrodes CH1, CH2, and CH3 are coupled to channels CH4, CH5, and CH6 after passing through the tissue of the patient 24 using the relays shown in FIG. 5. The controller 42 receives signal 412 representing the respective measured voltages and currents from channels CH1, CH2, and CH3, V 1 、V 2 、and V​3 Generate respective command signals 418 such that each of them has the same amplitude and phase (i.e., is virtually short-circuited). Similarly, the controller 42 receives signals 412 from channels CH4, CH5, and CH6, and V 4 V 5 and V 6 each have the same amplitude and the same phase, but are different from the amplitudes and phases of V 1 V 2 and V 3 ; thus, generate respective command signals 418 such that a desired sequence of IRE pulses flows between two groups of channels (and as a result, between two groups of electrodes 34 coupled to these channels).

[0054] As an example of monopolar IRE with "virtually short-circuited electrodes", electrodes CH1, CH2, and CH3 are selected as one enlarged electrode, while the return patch 66 functions as a return electrode for the IRE ablation signals emitted from electrodes CH1, CH2, and CH3. The return patch 66 is coupled to respective modules 502 of channels CH1, CH2, and CH3 by relays BP 1 BP 2 and BP 3 through connection 424. Similar to the bipolar IRE described above, the controller 42 receives signals 412 from channels CH1, CH2, and CH3, and generates respective command signals 413 such that each of V 1 V 2 and V 3 has the same amplitude and phase, thus virtually short-circuiting the electrodes 34 coupled to these channels.

[0055] The digital isolator 626 protects the subject 24 (FIG. 1) from unwanted voltages and currents.

[0056] Switch FO 1 Relay SO 1 BP 1 N 1and 610, and the analog multiplexer 622 are driven by the controller 42. For simplicity, the respective control lines are not shown in FIG. 6.

[0057] It should be understood that the embodiments described above are given by way of example, and the present invention is not limited to those specifically illustrated and described hereinabove. Rather, the scope of the present invention includes both the various combinations and sub - combinations of the features described hereinabove, as well as those variations and modifications thereof which would occur to those skilled in the art upon reading the foregoing description and which are not disclosed in the prior art.

[0058] 〔Embodiment〕 (1) A medical device for irreversible electroporation, A probe, An insertion tube configured for insertion into a body cavity of a patient, A distal assembly including a plurality of electrodes configured to contact tissue within the body cavity, the distal assembly being connected to the distal side of the insertion tube A probe comprising: An electrical signal generator configured to apply a biphasic electrical pulse to at least one group of two or more of the electrodes with sufficient energy to irreversibly electroporate the tissue contacting the electrodes within the at least one group, A controller coupled to measure a time - varying voltage difference between the electrodes within the at least one group and to adjust the biphasic electrical pulse applied to the electrodes within the at least one group so that the voltage difference does not exceed a predetermined threshold at any point during the application of the biphasic electrical pulse, An apparatus comprising: (2) The apparatus according to Embodiment 1, wherein the controller is configured to adjust the amplitude of the biphasic electrical pulse so as to compensate for the difference in the respective peak voltages measured for any pair of the electrodes in the at least one group. (3) The controller is configured to adjust the phase of the biphasic electrical pulse so as to compensate for the phase offset between each of the voltage waveforms measured in any pair of the electrodes of the at least one group, according to the apparatus of Embodiment 1. (4) The distal assembly comprises a balloon, the balloon is connected to the distal side of the insertion tube, and is configured to be inflated within the body cavity by the fluid flowing through the insertion tube into the balloon, according to the apparatus of Embodiment 1. (5) Comprising a common electrode configured to be fixed to a position on the patient's body, the biphasic electrical pulse passes through the body from the plurality of electrodes to the common electrode to irreversibly electroporate the tissue in monopolar mode, according to the apparatus of Embodiment 1.

[0059] (6) The at least one group comprises a first group and a second group, the biphasic electrical pulse is applied between the electrodes of the first group and the electrodes of the second group in bipolar mode, the controller measures the time-varying voltage difference between the electrodes of the first group and the electrodes of the second group, and is coupled to adjust the biphasic electrical pulse applied to the electrodes of the first group and the electrodes of the second group so that the voltage difference between the electrodes of the first group and the electrodes of the second group includes a predetermined train of biphasic electrical pulses, according to the apparatus of Embodiment 1. (7) A method for a medical treatment using irreversible electroporation, which comprises preparing a probe for insertion into a body cavity of a patient, the probe comprising an insertion tube, a plurality of electrodes configured to contact tissue within the body cavity, and a distal assembly connected to the distal side of the insertion tube and Applying a biphasic electrical pulse simultaneously to at least one group consisting of two or more of said electrodes with sufficient energy to irreversibly electroporate the tissue in contact with the electrodes within said at least one group, Measuring a time-varying voltage difference between the electrodes within said at least one group and adjusting the biphasic electrical pulse applied to the electrodes within said at least one group such that the voltage difference does not exceed a predetermined threshold at any point during the application of the biphasic electrical pulse, A method comprising. (8) Adjusting the biphasic electrical pulse comprises adjusting the amplitude of the biphasic electrical pulse to compensate for the difference in respective peak voltages measured in any pair of the electrodes of said at least one group, the method according to embodiment 7. (9) Adjusting the biphasic electrical pulse comprises adjusting the phase of the biphasic electrical pulse to compensate for the phase offset between the respective voltage waveforms measured in any pair of the electrodes of said at least one group, the method according to embodiment 7. (10) The distal assembly comprises a balloon, the balloon is connected to the distal side of the insertion tube and is configured to be inflated within the body cavity by fluid flowing through the insertion tube to the balloon, the method according to embodiment 7.

[0060] (11) Fixing a common electrode at a position on the patient's body, the biphasic electrical pulse irreversibly electroporating the tissue in monopolar mode by passing through the body from the plurality of electrodes to the common electrode, the method according to embodiment 7. (12) The at least one group comprises a first group and a second group, and applying the biphasic electrical pulse comprises applying the biphasic electrical pulse in a bipolar mode between the electrodes of the first group and the electrodes of the second group, measuring a time-varying voltage difference between the electrodes of the first group and the electrodes of the second group, and adjusting the biphasic electrical pulse applied to the electrodes of the first group and the electrodes of the second group such that the voltage difference between the electrodes of the first group and the electrodes of the second group includes a predetermined sequence of biphasic electrical pulses, the method according to embodiment 7.

Claims

1. A medical device for irreversible electroporation, comprising a probe, comprising an insertion tube configured for insertion into a body cavity of a patient, and a distal assembly having a plurality of electrodes configured to contact tissue within the body cavity, the distal assembly being connected to a distal side of the insertion tube ; an electrical signal generator configured to apply a biphasic electrical pulse simultaneously to at least one group of two or more of the electrodes with sufficient energy to irreversibly electroporate the tissue contacting the electrodes within the at least one group; a controller coupled to measure a time-varying voltage of each of the electrodes within the at least one group and to adjust the biphasic electrical pulse applied to the electrodes within the at least one group such that the voltages measured at each of the electrodes within the at least one group have the same amplitude and the same phase during application of the biphasic electrical pulse; a device comprising the above.

2. The device according to claim 1, wherein the controller is configured to adjust the amplitude of the biphasic electrical pulse to compensate for a difference in respective peak voltages measured at any pair of the electrodes of the at least one group.

3. The device according to claim 1, wherein the controller is configured to adjust the phase of the biphasic electrical pulse to compensate for a phase offset between respective voltage waveforms measured at any pair of the electrodes of the at least one group.

4. The device according to claim 1, wherein the distal assembly comprises a balloon, the balloon being connected to a distal side of the insertion tube and configured to be inflated within the body cavity by fluid flowing through the insertion tube to the balloon.

5. The device according to claim 1, further comprising a common electrode configured to be fixed at a location on the patient's body, wherein the biphasic electrical pulse irreversibly electroporates the tissue in a monopolar mode by passing through the body from the plurality of electrodes to the common electrode.

6. The at least one group comprises a first group and a second group, and the biphasic electrical pulse is applied between the electrodes of the first group and the electrodes of the second group in a bipolar mode. The controller measures the time-varying voltages of the respective electrodes within the first group and the second group, and during the application of the biphasic electrical pulse, the voltages measured at the respective electrodes within the first group have the same amplitude and the same phase, and the voltages measured at the respective electrodes within the second group have the same amplitude and the same phase. The apparatus according to claim 1, wherein the biphasic electrical pulse applied to the electrodes of the first group and the second group is adjusted.

7. A method of operating a medical device according to claim 1, wherein the electrical signal generator applies a biphasic electrical pulse simultaneously to at least one group consisting of two or more of the electrodes with sufficient energy to irreversibly electroporate the tissue in contact with the electrodes within the at least one group. wherein the controller measures the time-varying voltages of the respective electrodes within the at least one group, and during the application of the biphasic electrical pulse, adjusts the biphasic electrical pulse applied to the electrodes within the at least one group such that the voltages measured at the respective electrodes within the at least one group have the same amplitude and the same phase. A method comprising the steps of:

8. Adjusting the biphasic electrical pulse includes the controller adjusting the amplitude of the biphasic electrical pulse to compensate for the difference in the respective peak voltages measured at any pair of the electrodes of the at least one group. The method according to claim 7.

9. Adjusting the biphasic electrical pulse includes the controller adjusting the phase of the biphasic electrical pulse to compensate for the phase offset between the respective voltage waveforms measured at any pair of the electrodes of the at least one group. The method according to claim 7.

10. The method according to claim 7, wherein the distal assembly comprises a balloon, the balloon is connected to the distal side of the insertion tube, and is configured to be inflated in the body cavity by a fluid flowing through the insertion tube into the balloon.

11. The at least one group comprises a first group and a second group. Applying the biphasic electrical pulse includes the electrical signal generator applying the biphasic electrical pulse in a bipolar mode between the electrodes of the first group and the electrodes of the second group. Adjusting the biphasic electrical pulse includes the controller measuring the time-varying voltages of the respective electrodes in the first group and the second group, and during the application of the biphasic electrical pulse, the voltages measured at the respective electrodes in the first group have the same amplitude and the same phase, and the voltages measured at the respective electrodes in the second group have the same amplitude and the same phase, and adjusting the biphasic electrical pulse applied to the electrodes of the first group and the second group. The method according to claim 7.

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