Initiating IRE generation using a lamp

Abstract

To perform ablation using irreversible electroporation (IRE).SOLUTION: A method for ablating tissue in a subject includes providing a probe with an electrode to be inserted into a lumen of the subject, so that the electrode is in proximity to the tissue to be ablated. An immobilizing signal is injected into the subject via the electrode for immobilizing the subject. When the subject is immobilized, an ablation signal is injected via the electrode into the subject, the ablation signal being configured to ablate the tissue of the subject by irreversible electroporation. The ablation signal has at least one train of first pulses, where each of the first pulses in the at least one train has a first pulse absolute amplitude, and the immobilizing signal has one or more trains of second pulses, where each of the second pulses in the one or more trains has a second pulse absolute amplitude less than the first pulse absolute amplitude.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] (Cross-reference of related applications) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 159,412, filed March 10, 2021, which is incorporated herein by reference.

[0002] (Field of Invention) This disclosure generally relates to ablation used in surgical procedures, and more specifically to ablation performed using irreversible electroporation (IRE). [Background technology]

[0003] IRE is a soft tissue ablation technique that applies short pulses of a strong electric field to create permanent, and therefore lethal, nanopores within the cell membrane, thereby disrupting cellular homeostasis (internal physical and chemical conditions). Cell death after IRE is due to apoptosis (programmed cell death) and not necrosis (cell damage resulting from the action of the cell's own enzymes), as in all other heat or radiation-based ablation techniques. IRE is typically used in tumor ablation in areas where precision and preservation of the extracellular matrix, blood flow, and nerves are critical. Several examples of systems using IRE are provided below.

[0004] U.S. Patent No. 9,867,652 to Sano et al. describes an IRE applied through the vascular system of an organ to treat tumors deeply embedded within a tissue or organ, or to decellularize an organ to generate a scaffold from existing animal tissue with an existing complete vascular system. The patent states that "by gradually increasing the voltage and test cells within a given tissue, the point at which irreversible electroporation occurs can be determined."

[0005] U.S. Patent Application No. 2018 / 0289417(A1) to Schweitzer et al. describes an electroporation system and a method for pre-conditioning tissue for electroporation therapy. The electroporation generator includes an electroporation circuit and a pre-conditioning circuit. The pre-conditioning circuit is configured to be coupled to a pre-conditioning electrode to stimulate the patient's skeletal muscle tissue and is further configured to transmit a pre-conditioning signal to the pre-conditioning electrode.

[0006] U.S. Patent No. 10,286,108 to Davalos describes how IRE can be used to prepare tissue scaffolds. The scaffolds are derived from natural tissue and prepared using non-thermal, irreversible electroporation.

[0007] A more complete understanding of the present disclosure can be obtained by reading the following detailed description of the embodiments in conjunction with the drawings. [Brief explanation of the drawing]

[0008] [Figure 1] This is a schematic diagram of an IRE (irreversible electroporation) system used in ablation procedures. [Figure 2] This is a schematic voltage-time graph of a bipolar IRE pulse. [Figure 3] This is a schematic voltage-time graph of a bipolar pulse burst. [Figure 4] This is a schematic graph of the fixed signal and the IRE ablation signal. [Figure 5] This is a flowchart illustrating the steps of the IRE ablation procedure, showing the use of a fixed signal. [Modes for carrying out the invention]

[0009] Overview A fundamental problem with applying IRE ablation is that the subject may jump or convulse when the IRE pulse is first applied to them. Convulsions are caused by the high electric field of the high-voltage IRE pulse, resulting in muscular, skeletal, or diaphragmatic contractions of the subject. Convulsions can lead to traumatic situations, for example, if the catheter probe is initially positioned at the desired location within the myocardium.

[0010] First, instead of applying IRE pulses at their full voltage amplitude, embodiments of the present disclosure incorporate a ramp period into pulse generation. During the ramp period, the pulse amplitude is gradually increased while remaining below the effective IRE voltage. During the ramp period, the pulse amplitude is sufficiently low that no IRE occurs. After the ramp period, the full IRE voltage amplitude may be applied, resulting in IRE occurring.

[0011] The initial low-voltage pulse fixes the subject's muscles without causing IRE, so the subject remains fixed and does not spasm when the full IRE voltage is achieved.

[0012] The ramp can take any convenient shape, such as linear or exponential. The typical length of the ramp period is approximately 0.5 seconds.

[0013] System Description Referring now to Figure 1, which is a schematic diagram of a multichannel IRE system 20 used in an IRE (irreversible electroporation) ablation procedure. In the depicted embodiment, physician 22 performs a multichannel IRE ablation procedure using the IRE system 20. Physician 22 performs the procedure on the heart 52 of subject 24 using an ablation catheter probe 26 having a distal end 28, the distal end 28 comprising a plurality of ablation electrodes 30 arranged along the length of the distal end.

[0014] The IRE system 20 includes a processor 32 and an IRE module 34, the IRE module including an IRE generator 36 and an IRE controller 38. An IRE generator similar to the generator 36 is described in U.S. Patent Application No. 16 / 701,989. As detailed below, the IRE generator 36 generates a series of electrical pulses directed to a selected electrode 30 to generate a current 72 in between in order to perform an IRE procedure. The waveform (timing and amplitude) of the series of electrical pulses is controlled by the IRE controller 38. The processor 32 also operates the input and output interfaces between the IRE system 20 and the physician 22, as detailed below.

[0015] The processor 32 and the IRE controller 38 each typically include a programmable processor, which is programmed with software and / or firmware to perform the functions described herein. Alternatively, or in addition to, the processor and controller may include hardwired and / or programmable hardware logic circuits to perform at least some of these functions. For simplification, the processor 32 and the IRE controller 38 are shown in the figure as separate monolithic functional blocks, but in practice, some of these functions may be combined within a single processing and control unit. In some embodiments, the IRE controller 38 typically resides within the IRE module 34, as high-speed control signals are sent from the IRE controller to the IRE generator 36. However, the IRE controller 38 may reside within the processor if sufficiently high-speed signals can be sent from the processor 32 to the IRE generator 36.

[0016] Processor 32 and IRE module 34 typically reside within console 40. Console 40 includes an input device 42, such as a keyboard and mouse, operated by physician 22. Display screen 44 is positioned proximate to console 40. Display screen 44 may optionally include a touch screen, thereby providing another input device.

[0017] IRE system 20 may further include one or more of the following modules (typically residing within console 40). · An electrocardiogram (ECG) module 46 is coupled via cable 48 to ECG electrodes 50 attached to subject 24. ECG module 46 is configured to measure the electrical activity of subject 24's heart 52. · A temperature module 54 is coupled to a temperature sensor 56, such as a thermocouple, positioned adjacent to each electrode 30 on the distal end 28 of catheter 26, and is configured to measure the temperature of adjacent tissue 58. · A tracking module 60 is coupled to one or more electromagnetic position sensors 61 within distal end 28. In the presence of an external magnetic field generated by magnetic field generator 62, the electromagnetic position sensors output signals that vary with the position of the sensors. Based on these signals, tracking module 60 can identify the position of electrodes 30 within heart 52.

[0018] The position tracking method using an external magnetic field is implemented in the CARTO (trademark) system manufactured by Biosense Webster Inc., Irvine, California, and is described in detail in U.S. Patent Nos. 5,391,199, 6,690,963, 6,484,118, 6,239,724, 6,618,612, and 6,332,089, International Publication No. 96 / 05768, and U.S. Patent Application Publication Nos. 2002 / 0065455(A1), 2003 / 0120150(A1), and 2004 / 0068178(A1).

[0019] Alternatively, or in addition to the above, module 60 may use a tracking system based on the current transmitted by the electrode 30 or the impedance seen from the electrode 30. In such a system, module 60 estimates the position of a given electrode 30 in response to the current or impedance between the given electrode and a plurality of surface electrodes 63 bonded to the skin of the subject 24. For example, the Advanced Current Location (ACL) system manufactured by Biosense-Webster (Irvine, California), described in U.S. Patent No. 8,456,182, is such a tracking system.

[0020] The catheter 26 is connected to the console 40 via an electrical interface 64, such as a port or socket. Thus, the IRE signal is transmitted to the distal end 28 via the interface 64. Similarly, signals for tracking the position of the distal end 28 and / or signals for tracking the temperature of the tissue 58 are received by the processor 32 via the interface 64 and can be applied by the IRE controller 38 when controlling the pulses generated by the IRE generator 36.

[0021] An external electrode 65, or "return patch," may be additionally coupled externally between the subject 24, typically on the skin of the subject's torso, and the IRE generator 36.

[0022] The IRE signals generated by the IRE module are described below with reference to Figures 2 and 3 and Table I. Except as otherwise provided below, the signals generated by the module are used by the selected electrode 30 to ablate the tissue 58 adjacent to the electrode.

[0023] Figure 2 is a schematic diagram of a voltage-to-time graph of a bipolar IRE pulse 100 according to one embodiment of the present disclosure.

[0024] Graph 102 depicts the voltage V of the bipolar IRE pulse 100 as a function of time t. The bipolar IRE pulse includes a positive pulse 104 and a negative pulse 106, where the terms "positive" and "negative" refer to the arbitrarily selected polarity of the two selected electrodes 30 to which the bipolar pulse is applied. The amplitude of the positive pulse 104 is denoted as V+, and the pulse duration is denoted as t+. Similarly, the amplitude of the negative pulse 106 is denoted as V-, and the pulse duration is denoted as t-. The time between the positive pulse 104 and the negative pulse 106 is t 間隔 It is labeled as such. Typical values ​​for the parameters of bipolar pulse 100 are shown in Table 1 below.

[0025] Figure 3 is a schematic diagram of a voltage-to-time graph of a bipolar pulse burst 200 according to one embodiment of the present disclosure.

[0026] In an IRE procedure, the IRE signal is typically carried between a selected pair of electrodes 30 as one or more bursts 200, as depicted by graph 202, so that one of the pairs can be considered to act as the injection electrode, while the other acts as the return electrode. Alternatively, the IRE signal may be carried between one selected electrode 30 and an external electrode 65, in which case the selected electrode 30 can be considered to act as the injection electrode, while the external electrode 65 acts as the return electrode.

[0027] Burst 200 is, N T It includes pulse train 204, each train being N P Includes bipolar pulse 100, N T , N P is a positive integer. The length of pulse train 204 is t. T It is labeled as such. The period of the bipolar pulse 100 in pulse train 204 is t PP Labeled as such, the spacing between consecutive columns is Δ T It is labeled as such, and no signal is applied during this time. Typical values ​​for the signal definition parameters of the burst 200 IRE ablation signal are shown in Table 1 below.

[0028] [Table 1]

[0029] fixed signal As is evident from Figures 2 and 3, and Table I, the IRE signal delivered to the subject 24 via one or a pair of selected electrodes 30 includes a high-voltage pulse, i.e., a pulse with an amplitude of up to 2000V. The inventors observed that when the IRE signal was first delivered to the subject, the subject may convulse, and that the convulsions were thought to be caused by the high voltage / field of the IRE pulse, which triggers skeletal or diaphragmatic contractions of the subject's muscles.

[0030] Seizures in the subject can cause trauma. Seizures can also lead to displacement of the electrode 30 from its initial position, thus requiring repositioning of the electrode, which increases the duration of the ablation procedure.

[0031] An example of this disclosure involves preventing a subject from convulsing by injecting a fixation signal into the subject 24 before injecting an IRE ablation signal. The fixation signal fixes the subject's muscles so that the subject no longer convulses when the IRE ablation signal is injected. Typically, the fixation signal is generally similar to the IRE ablation signal, except that the fixation signal has a lower absolute amplitude. The fixation signal is described in detail below.

[0032] In one embodiment of the present disclosure, the fixed signal comprises a set of pulse trains having monotonically increasing amplitudes, all of which have an absolute value smaller than the absolute value of the ablation IRE signal. The fixed signal is described with reference to Figure 4 below.

[0033] Figure 4 is a schematic graph 300 of an immobilization signal and an IRE ablation signal according to an embodiment of the present disclosure. Graph 300 is a voltage versus time graph, and a section 302 of the graph includes an immobilization signal, also referred to herein as immobilization signal 302. A section 306 of the graph includes an IRE ablation signal, which comes temporally after the immobilization signal as shown. The IRE ablation signal is also referred to herein as IRE ablation signal 306.

[0034] The parameters of the IRE ablation signal 306 are configured according to Table I. As an example, signal 306 is assumed to include four pulse trains 310, also referred to herein as burst 306. Each pulse train 310, V+, V-, t+, t-, t 間隔 、t PP 、t T 、N P is configured to have the same parameters, and the interval Δ T between consecutive pulse trains 310 is also as described in Table I.

[0035] The immobilization signal 302 includes one or more pulse trains 314A, 314B, 314C,... generally referred to as pulse train 314. As an example, signal 302 is assumed to include three pulse trains 314. In one embodiment of the present disclosure, except for the pulse amplitudes V+ and V-, the pulse train 314 has the same parameters as the pulse train 310. Further, the interval between the pulse trains 314 is the same as that of the pulse train 310, and the interval between the last pulse train of the immobilization signal and the initial pulse train of the ablation signal is also the same.

[0036] In the case of the ablation signal 306, the amplitude of the pulses within a given pulse train of the immobilization signal is constant. However, in contrast to the ablation signal 306, herein the amplitudes of consecutive pulse trains of the immobilization signal called V+ imm and V- imm are not equal to each other, but rather vary monotonically with time. That is, the value of V+ imm increases monotonically with time, and V- immThe value of [[ID=]] monotonically decreases over time. Therefore, the absolute value of the amplitude of the consecutive pulse train of the immobilization signal monotonically increases in a ramp-like manner.

[0037] In the disclosed embodiment, the amplitude of the immobilization signal pulse train changes from the lower limit values of the amplitudes V+, V− of the ablation signal 306 to the upper limit values “u” of the amplitudes V+, V−, and 0 < b < u < 1. The change can be linear or non-linear, for example, exponential. In the disclosed embodiment, b = 20% and u = 70%, but other values of u and b are possible under the condition of following the above inequality. Typically, as illustrated in FIG. 4, the overall time ΔT imm of the immobilization signal 302 is approximately 0.5 seconds, but an overall time greater than or less than 0.5 seconds is possible.

[0038] Typical values of the amplitude of the immobilization signal pulse train and of the overall time of the immobilization signal are shown in Table II listing the signal definition parameters of the immobilization signal.

[0039]

Table 2

[0040] FIG. 5 is a flowchart of the steps of an IRE ablation procedure illustrating the use of an immobilization signal according to an embodiment of the present disclosure.

[0041] The IRE ablation procedure typically includes applying a plurality of bursts 200 of the IRE signal between different selected pairs of electrodes 30 and / or between different selected electrodes 30 and an external electrode 65. (Each burst is typically applied sequentially to the first, second, third,... pairs of electrodes.) In an embodiment of the present disclosure, the immobilization signal 302 can be applied before each of the bursts. Alternatively, the immobilization signal 302 can be applied before selected ones of the bursts. Further alternatively, the immobilization signal 302 can be applied only before the first of the bursts.

[0042] For the sake of simplicity in the following description, it is assumed that the IRE procedure involves one burst 200 delivered between a pair of electrodes, so that one electrode 30 acts as the injection electrode, and the other electrode of the pair, which may be electrode 30 or electrode 65, acts as the return electrode. Those skilled in the art may modify the description by applying it mutatis mutandis to other cases, namely, multiple bursts 200 applied to two or more pairs of electrodes.

[0043] In the initial setup step 400, the physician 22 selects the IRE signal parameters to be used for the procedure. The values ​​are listed in Table I and selected as described above with reference to Figures 2 and 3. In addition, the physician 22 selects the values ​​for the fixed signal parameters, listed in Table II and selected as described above with reference to Figure 4. The selection can be carried out in any convenient way, such as by displaying protocols with preset values ​​for the IRE signal parameters and fixed signal parameters on the screen 44, and by allowing the physician to select a specific protocol.

[0044] In the setup step, the physician also selects a pair of electrodes to be used to inject the IRE and immobilization signals. The pair of electrodes may comprise one electrode 30 acting as the injection electrode and another electrode 30 acting as the return electrode. Alternatively, the pair may comprise one electrode 30 acting as the injection electrode and an external electrode 65 acting as the return electrode. With respect to signal parameters, selection may also allow the physician to select the electrode pair to be used for IRE ablation by displaying a pre-configured protocol on screen 44.

[0045] In insertion step 404, to initiate the procedure, physician 22 inserts catheter 26 into subject 24 through the subject's lumen and then navigates the catheter using control handle 70 so that the selected injection electrode 30 is close to a selected portion of tissue 58 called the target tissue to be ablated. Processor 32 uses tracking module 60 for navigation. The module typically displays the position of the distal end 28 and the electrode 30 (including the injection electrode 30 selected in step 400) on an image of the heart 52 presented on screen 44.

[0046] When the injection electrode is positioned close to the target tissue, the physician 22 initiates IRE ablation by providing a control signal to the processor 32 by any convenient means, such as using the control handle 70, the input device 42, or a foot switch (not shown).

[0047] Upon receiving a control signal, the processor 32 implements the fixation step 408 and subsequently implements the conclusion ablation step 412.

[0048] In the immobilization step 408, the processor uses the IRE module 34 to generate an immobilization signal 302 configured according to the values ​​selected in the setup step 400 and generally illustrated in Figure 4. The processor directs the immobilization signal to the injection electrode 30, which in turn injects the immobilization signal into the subject 24. The immobilization signal immobilizes the subject 24.

[0049] Upon completion of the injection of the immobilization signal, when the subject 24 is immobilized, the processor proceeds to the ablation step 412. In step 412, the processor uses the IRE module 34 to generate an ablation signal 308 configured according to the values ​​selected in the setup step 400 and generally illustrated in Figure 4. For step 408, in step 412, the processor directs the ablation signal to the injection electrode 30, and as a result, the electrode injects the ablation signal into the subject 24 and ablates the target tissue.

[0050] As used herein, the terms “about” or “approximately” for any number or range of numbers indicate a preferred dimensional tolerance that would enable the entity to function in accordance with the intended purpose set forth herein. More specifically, “about” or “approximately” may refer to a range of values ​​within ±20% of the listed values; for example, “about 90%” may refer to a range of values ​​from 72% to 108%, and “approximately 0.5 seconds” may refer to a range of values ​​from 0.4 seconds to 0.6 seconds. [Examples]

[0051] Example 1. A method for ablating tissue (58) within a subject (24), To provide a probe (26) having an electrode (30) configured to be inserted into the lumen of a subject, thereby providing that the electrode is in close proximity to the tissue to be ablated, The process involves injecting an immobilization signal, configured to immobilize the subject, into the subject via electrodes, The procedure includes injecting an ablation signal into a subject via electrodes while the subject is immobilized, wherein the ablation signal is configured to ablate the subject's tissue by irreversible electroporation. A method comprising an ablation signal comprising at least one column of first pulses, each of the first pulses in at least one column having a first pulse absolute amplitude, and a fixation signal comprising one or more columns of second pulses, each of the second pulses in one or more columns having a second pulse absolute amplitude smaller than the first pulse absolute amplitude.

[0052] Example 2. The method according to Example 1, wherein the fixed signal comprises multiple rows of second pulses, and the absolute amplitude of each of the multiple second pulses increases monotonically over time.

[0053] Example 3. The method according to Example 2, wherein the monotonically increasing function is linear.

[0054] Example 4. The method according to Example 2, wherein the monotonically increasing function is non-linear.

[0055] Example 5. The method according to Example 1, wherein each row in at least one column of the first pulse and each row in one or more columns of the second pulse contains multiple pulses.

[0056] Example 6. The method according to Example 1, wherein the absolute amplitude of the second pulse is 20% to 70% of the absolute amplitude of the first pulse.

[0057] Example 7. The method according to Example 1, wherein the first pulse and the second pulse include a bipolar pulse.

[0058] Example 8. The method according to Example 1, wherein the overall time of the fixed signal is in the range of 0.4 seconds to 0.6 seconds.

[0059] Example 9. The method according to Example 1, wherein the probe comprises an additional electrode (30) configured to receive an injected ablation signal and an injected immobilization signal.

[0060] Example 10. The method according to Example 1, further comprising an external electrode (65) located on the skin of a subject, configured to receive injected ablation signals and injected immobilization signals.

[0061] Example 11. A device for ablating tissue (58) within a subject (24), A probe (26) comprising an electrode (30) configured to be inserted into the lumen of a subject, wherein the electrode is in close proximity to the tissue to be ablated, and A processor (32), The process involves injecting an immobilization signal, configured to immobilize the subject, into the subject via electrodes, A processor is configured to inject an ablation signal into a subject via electrodes while the subject is immobilized, wherein the ablation signal is configured to ablate the subject's tissue by irreversible electroporation. An apparatus wherein the ablation signal comprises at least one column of first pulses, each of the first pulses in at least one column having a first pulse absolute amplitude, and the fixation signal comprises one or more columns of second pulses, each of the second pulses in one or more columns having a second pulse absolute amplitude smaller than the first pulse absolute amplitude.

[0062] The embodiments described above are for illustrative purposes only, and it should be understood that this disclosure is not limited to those specifically illustrated and described above. Rather, the scope of this disclosure includes both combinations and partial combinations of the various features described above, as well as variations and modifications thereof not disclosed in the prior art, which would be conceived by those skilled in the art upon reading the foregoing description.

[0063] [Implementation Method] (1) A method for ablating tissue within a subject, To provide a probe comprising an electrode configured to be inserted into the lumen of the subject, wherein the electrode is in close proximity to the tissue to be ablated, An immobilization signal configured to immobilize the subject is injected into the subject via the electrodes. The procedure includes, while the subject is immobilized, injecting an ablation signal into the subject via the electrodes, wherein the ablation signal is configured to ablate the subject's tissue by irreversible electroporation. A method wherein the ablation signal comprises at least one column of first pulses, each of the first pulses in the at least one column having a first pulse absolute amplitude, and the fixing signal comprises one or more columns of second pulses, each of the second pulses in the one or more columns having a second pulse absolute amplitude smaller than the first pulse absolute amplitude. (2) The method according to Embodiment 1, wherein the fixed signal comprises a plurality of rows of the second pulses, and the absolute amplitude of each of the plurality of the second pulses increases monotonically over time. (3) The method according to Embodiment 2, wherein the monotonically increasing function is linear. (4) The method according to Embodiment 2, wherein the monotonically increasing is non-linear. (5) The method according to Embodiment 1, wherein each row in at least one row of the first pulses and each row in one or more rows of the second pulses comprises a plurality of pulses.

[0064] (6) The method according to Embodiment 1, wherein the absolute amplitude of the second pulse is 20% to 70% of the absolute amplitude of the first pulse. (7) The method according to Embodiment 1, wherein the first pulse and the second pulse include a bipolar pulse. (8) The method according to Embodiment 1, wherein the overall time of the fixed signal is in the range of 0.4 seconds to 0.6 seconds. (9) The method according to Embodiment 1, wherein the probe comprises a further electrode configured to receive the injected ablation signal and the injected immobilization signal. (10) The method according to Embodiment 1, comprising external electrodes located on the skin of the subject, configured to receive the injected ablation signal and the injected immobilization signal.

[0065] (11) A device for ablating tissue within a subject, A probe comprising an electrode configured to be inserted into the lumen of the subject, wherein the electrode is in close proximity to the tissue to be ablated, It is a processor, An immobilization signal configured to immobilize the subject is injected into the subject via the electrodes. A processor is configured to inject an ablation signal into the subject via the electrodes while the subject is immobilized, wherein the ablation signal is configured to ablate the subject's tissue by irreversible electroporation. An apparatus wherein the ablation signal comprises at least one column of first pulses, each of the first pulses in the at least one column having a first pulse absolute amplitude, and the fixation signal comprises one or more columns of second pulses, each of the second pulses in the one or more columns having a second pulse absolute amplitude smaller than the first pulse absolute amplitude. (12) The apparatus according to Embodiment 11, wherein the fixed signal comprises a plurality of rows of the second pulses, and the absolute amplitude of each of the plurality of the second pulses increases monotonically over time. (13) The apparatus according to Embodiment 12, wherein the monotonically increasing function is linear. (14) The apparatus according to Embodiment 12, wherein the monotonically increasing is non-linear. (15) The apparatus according to Embodiment 11, wherein each row in at least one row of the first pulses and each row in one or more rows of the second pulses comprises a plurality of pulses.

[0066] (16) The apparatus according to Embodiment 11, wherein the absolute amplitude of the second pulse is 20% to 70% of the absolute amplitude of the first pulse. (17) The apparatus according to Embodiment 11, wherein the first pulse and the second pulse include a bipolar pulse. (18) The apparatus according to Embodiment 11, wherein the overall time of the fixed signal is in the range of 0.4 seconds to 0.6 seconds. (19) The apparatus according to embodiment 11, wherein the probe comprises a further electrode configured to receive the injected ablation signal and the injected immobilization signal. (20) The apparatus according to embodiment 11, comprising external electrodes located on the skin of the subject, configured to receive the injected ablation signal and the injected immobilization signal.

Claims

1. A device for ablating tissue within a subject, A probe comprising an electrode configured to be inserted into the lumen of the subject, wherein the electrode is in close proximity to the tissue to be ablated, It is a processor, An immobilization signal configured to immobilize the subject is injected into the subject via the electrodes. A processor is configured to inject an ablation signal into the subject via the electrodes while the subject is immobilized, wherein the ablation signal is configured to ablate the subject's tissue by irreversible electroporation. The ablation signal comprises at least one column of first pulses, and each of the first pulses in the at least one column has a first pulse absolute amplitude. The immobilization signal comprises a plurality of rows of second pulses, each of which has a second pulse absolute amplitude smaller than the first pulse absolute amplitude and is not configured to ablate the tissue. A device in which the absolute amplitude of the second pulse increases monotonically over time.

2. The apparatus according to claim 1, wherein the monotonically increasing function is linear.

3. The apparatus according to claim 1, wherein the monotonically increasing portion is non-linear.

4. The apparatus according to claim 1, wherein at least one row of the first pulses includes a plurality of pulses.

5. The apparatus according to claim 1, wherein the absolute amplitude of the second pulse is 20% to 70% of the absolute amplitude of the first pulse.

6. The apparatus according to claim 1, wherein the first pulse and the second pulse include a bipolar pulse.

7. The apparatus according to claim 1, wherein the overall time of the fixed signal is in the range of 0.4 seconds to 0.6 seconds.

8. The apparatus according to claim 1, wherein the probe comprises a further electrode configured to receive the injected ablation signal and the injected immobilization signal.

9. The apparatus according to claim 1, further comprising an external electrode located on the skin of the subject, configured to receive the injected ablation signal and the injected immobilization signal.

Images