Irreversible electroporation pulse generation device, pulse control method and ablation equipment

Abstract

The invention discloses an irreversible electroporation pulse generation device, a pulse control method and ablation equipment, and belongs to the technical field of medical equipment. The irreversible electroporation pulse generation device comprises a pulse generation module and a control module. The control module is connected with the pulse generation module and used for controlling the pulse generation module to output bipolar pulse signals and controlling the time interval between adjacent pulses in the bipolar pulse signals; wherein the control module controls at least part of positive polarity pulses and at least part of negative polarity pulses in the bipolar pulse signals output by the pulse generation module to be connected end to end to form a first pulse sequence; the frequency of the first pulse sequence is greater than a frequency threshold value, so that the to-be-ablated tissue bearing the first pulse sequence is heated. According to the embodiment of the invention, an electric pulse waveform with a heat effect can be formed, so that an ablation area is expanded.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular, to an irreversible electroporation pulse generating device, a pulse control method, and an ablation device. Background Art

[0002] Irreversible electroporation (IRE) is a tissue ablation technique that creates permanent nanopores on the cell membrane through an extremely strong but extremely short electric field. By disturbing the cell homeostasis to cause cell death, it can be used for ablation of abnormal tissues, such as ablation of tumors. Different from traditional microwave ablation and radiofrequency ablation techniques, due to the extremely short pulse duration of IRE, the thermal effect generated is very small, which can avoid the problems of irreversible damage to adjacent tissue structures during the operation and the heat sink effect. However, the currently used irreversible electroporation technique has the problem of a small ablation area. Summary of the Invention

[0003] The present invention provides an irreversible electroporation pulse generating device, a pulse control method, and an ablation device to form an electric pulse waveform with a thermal effect, thereby expanding the ablation area.

[0004] In a first aspect, an embodiment of the present invention provides an irreversible electroporation pulse generating device, including:

[0005] A pulse generating module;

[0006] A control module, connected to the pulse generating module, for controlling the pulse generating module to output a bipolar pulse signal and controlling the time interval between adjacent pulses in the bipolar pulse signal; wherein, the control module controls at least some of the positive polarity pulses and at least some of the negative polarity pulses in the bipolar pulse signal output by the pulse generating module to be connected end to end to form a first pulse sequence; the frequency of the first pulse sequence is greater than a frequency threshold value to heat up the tissue to be ablated that receives the first pulse sequence.

[0007] Optionally, the pulse generating module includes:

[0008] A first pulse generating circuit, connected to the control module, for generating each of the positive polarity pulses in the bipolar pulse signal;

[0009] A second pulse generating circuit, connected to the control module, for generating each of the negative polarity pulses in the bipolar pulse signal.

[0010] Optionally, the first pulse sequence includes a plurality of first positive polarity pulses and a plurality of first negative polarity pulses;

[0011] The first pulse generating circuit includes: a first pulse generating sub-module, connected to the control module, for generating the first positive polarity pulses;

[0012] The second pulse generation circuit includes: a second pulse generation sub-module, connected to the control module, for generating the first negative-polarity pulse;

[0013] The control module is used to control the first pulse generation sub-module and the second pulse generation sub-module to alternately output, so that the first positive-polarity pulses and the first negative-polarity pulses are connected end to end to form the first pulse sequence.

[0014] Optionally, the bipolar pulse signal further includes: a second pulse sequence; the second pulse sequence includes at least one of a second positive-polarity pulse and a second negative-polarity pulse; and in the second pulse sequence, there is a time interval between adjacent pulses; wherein, the frequency of the second pulse sequence is less than the frequency threshold;

[0015] The first pulse generation circuit further includes: a third pulse generation sub-module; the third pulse generation sub-module is connected to the control module, for generating the second positive-polarity pulse;

[0016] And / or, the second pulse generation circuit further includes: a fifth pulse generation sub-module; the fifth pulse generation sub-module is connected to the control module, for generating the second negative-polarity pulse.

[0017] Optionally, the second pulse sequence further includes at least one of a third positive-polarity pulse and a third negative-polarity pulse; wherein, the pulse width and / or amplitude of the third positive-polarity pulse are different from those of the second positive-polarity pulse, and the pulse width and / or amplitude of the third negative-polarity pulse are different from those of the second negative-polarity pulse;

[0018] The first pulse generation circuit further includes: a fourth pulse generation sub-module; the fourth pulse generation sub-module is connected to the control module, for generating the third positive-polarity pulse;

[0019] And / or, the second pulse generation circuit further includes: a sixth pulse generation sub-module; the sixth pulse generation sub-module is connected to the control module, for generating the third negative-polarity pulse.

[0020] Optionally, the amplitude of the first positive-polarity pulse is less than the amplitude of the second positive-polarity pulse and less than the amplitude of the third positive-polarity pulse; among the second positive-polarity pulse and the third positive-polarity pulse, the one with the smaller amplitude has a wider pulse width;

[0021] The amplitude of the first negative-polarity pulse is less than the amplitude of the second negative-polarity pulse and less than the amplitude of the third negative-polarity pulse; among the second negative-polarity pulse and the third negative-polarity pulse, the one with the smaller amplitude has a wider pulse width.

[0022] Optionally, the irreversible electroporation pulse generating device further includes:

[0023] A power management module, which is respectively connected to the power supply system, the control module and the pulse generating module; the power management module is used to convert the power supplied by the power supply system and supply power to the control module and the pulse generating module;

[0024] And / or,

[0025] An output switching module, the output switching module is respectively connected to the control module and the pulse generating module, and is connected to each electrode needle in the ablation device; the output switching module is used to receive the bipolar pulse signal and select the electrode needle receiving the bipolar pulse signal according to the control of the control module.

[0026] Optionally, the bipolar pulse signal is a square wave signal;

[0027] And / or, the amplitude of the first pulse sequence is between 0 - 1 kV;

[0028] And / or, the frequency of the first pulse sequence is between 10 Hz - 5 MHz;

[0029] And / or, the pulse width of any pulse in the first pulse sequence is between 100 ns - 10 μs.

[0030] In a second aspect, an embodiment of the present invention further provides an ablation device, including: the irreversible electroporation pulse generating device provided in any embodiment of the present invention.

[0031] Optionally, the ablation device further includes:

[0032] A power supply system, connected to the power management module in the irreversible electroporation pulse generating device;

[0033] And / or, an output interface and a plurality of electrode needles, the output switching module in the irreversible electroporation pulse generating device is connected to each of the electrode needles through the output interface;

[0034] And / or, a human - machine interaction module, connected to the control module.

[0035] In a third aspect, an embodiment of the present invention further provides a pulse control method, which is applied to the irreversible electroporation pulse generating device provided in any embodiment of the present invention, and the pulse control method includes:

[0036] High - frequency output stage: The control module controls the pulse generating module to output at least one first pulse sequence.

[0037] Optionally, the pulse generation module includes a first pulse generation submodule and a second pulse generation submodule; and the process in which the control module controls the pulse generation module to output the first pulse sequence includes:

[0038] Control the pulse generating module to continuously operate for a plurality of pulse cycles; the pulse cycles include:

[0039] Sending a first control signal to the first pulse generating submodule to control the first pulse generating submodule to output a first positive polarity pulse;

[0040] After the first control signal is sent, after a delay equal to the pulse width of the first positive polarity pulse, a second control signal is sent to the second pulse generating submodule to control the second pulse generating submodule to output a first negative polarity pulse;

[0041] Among them, starting from the issuance of the second control signal in the current pulse cycle, after a delay equal to the pulse width of the first negative polarity pulse, the next pulse cycle is controlled to start.

[0042] Optionally, the amplitude of the first pulse sequence is lower than a voltage threshold, and the high-frequency output stage includes one first pulse sequence;

[0043] or,

[0044] The amplitude of the first pulse sequence exceeds the voltage threshold, the high-frequency output stage includes at least two first pulse sequences, and there is a time interval between two adjacent first pulse sequences.

[0045] Optionally, the pulse control method further includes:

[0046] Low-frequency output stage: the control module controls the pulse generation module to output at least one second pulse sequence; the frequency of the first pulse sequence is greater than the frequency of the second pulse sequence.

[0047] Optionally, the second pulse sequence includes: at least one of a second positive polarity pulse, a second negative polarity pulse, a third positive polarity pulse and the third negative polarity pulse;

[0048] Among them, one of the second positive polarity pulse and the third positive polarity pulse is a nanosecond pulse, and the other is a microsecond pulse; one of the second negative polarity pulse and the third negative polarity pulse is a nanosecond pulse, and the other is a microsecond pulse; the amplitude of any of the nanosecond pulses is greater than the amplitude of any of the microsecond pulses.

[0049] Optionally, the pulse control method includes:

[0050] High-frequency mode, including the high-frequency output stage;

[0051] and / or,

[0052] Synergy mode, including the high-frequency output stage and the low-frequency output stage carried out at different times.

[0053] Optionally, when the pulse control method includes the synergy mode, in the synergy mode, the high-frequency output stage is carried out before the low-frequency output stage.

[0054] In an embodiment of the present invention, the control module controls the first pulse sequence in the bipolar pulse signal output by the pulse generation module to be a high-frequency pulse sequence, and applies the bipolar pulse signal containing the first pulse sequence to the tissue to be ablated, which is equivalent to applying electrical energy to the tissue to be ablated. Since there is no time interval between adjacent pulses in the first pulse sequence, the continuous pulses can make the frequency of the first pulse sequence higher, which is beneficial to heat accumulation, increase the temperature of the tissue to be ablated, achieve the purpose of cryothermal effect, and expand the ablation range. At the same time, the thermal effect can also bring a hemostatic effect synchronously and prevent needle tract metastasis when the electrode needle is withdrawn. In summary, compared with the existing irreversible electroporation electrical pulse waveform that does not generate a thermal effect, the embodiment of the present invention can provide a bipolar pulse signal with a cryothermal effect, thereby expanding the ablation area.

[0055] It should be understood that the content described in this part is not intended to identify the key or important features of the embodiments of the present invention, nor is it used to limit the scope of the present invention. Other features of the present invention will become easily understood through the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0057] Figure 1 is a schematic structural diagram of an irreversible electroporation pulse generation device provided by an embodiment of the present invention;

[0058] Figure 2 is a waveform schematic diagram of a first pulse sequence provided by an embodiment of the present invention;

[0059] Figure 3 is another waveform schematic diagram of a first pulse sequence provided by an embodiment of the present invention

[0060] Figures 4 - 6 is a waveform schematic diagram of three second pulse sequences provided by an embodiment of the present invention;

[0061] Figure 7 is a schematic structural diagram of another irreversible electroporation pulse generating device provided by an embodiment of the present invention;

[0062] Figure 8 is a schematic structural diagram of a first pulse generation sub-module provided by an embodiment of the present invention;

[0063] Figure 9 is a schematic structural diagram of an ablation device provided by an embodiment of the present invention;

[0064] Figure 10 is a schematic structural diagram of another ablation device provided by an embodiment of the present invention;

[0065] Figure 11 is a schematic waveform diagram of a bipolar pulse signal in a high-frequency mode provided by an embodiment of the present invention;

[0066] Figure 12 is a schematic waveform diagram of another bipolar pulse signal in a high-frequency mode provided by an embodiment of the present invention;

[0067] Figures 13 - 17 is a schematic waveform diagram of a bipolar pulse signal in five cooperative modes provided by an embodiment of the present invention;

[0068] Figures 18 - 41 is a schematic diagram of the results of a rabbit liver experiment provided by an embodiment of the present invention;

[0069] Figures 42 - 44 is a bar chart of the results of a rabbit liver experiment provided by an embodiment of the present invention. Detailed implementation manners

[0070] In order to enable those skilled in the art to better understand the solution of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0071] It should be noted that the terms "first", "second", etc. in the specification and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects, and do not necessarily describe a specific order or sequence. It should be understood that such data can be interchanged under appropriate circumstances so that the embodiments of the present invention described herein can be implemented in an order different from those illustrated or described herein. In addition, the terms "include" and "have" and any variations thereof are intended to cover non-exclusive inclusion.

[0072] An embodiment of the present invention provides an irreversible electroporation pulse generating device, which can provide a bipolar pulse signal including a first pulse sequence with high frequency, and form an electric pulse waveform with a thermal effect to expand the ablation area and improve the ablation effect of irreversible electroporation. Figure 1 It is a schematic structural diagram of an irreversible electroporation pulse generating device provided by an embodiment of the present invention. Refer to Figure 1 This irreversible electroporation pulse generating device includes: a pulse generating module 10 and a control module 20.

[0073] Among them, the control module 20 is connected to the pulse generating module 10, and is used to control the pulse generating module 10 to output a bipolar pulse signal and control the time interval between adjacent pulses in the bipolar pulse signal. Among them, each pulse in the bipolar pulse signal includes a plurality of positive-polarity pulses and a plurality of negative-polarity pulses. The control module 20 controls at least some of the positive-polarity pulses and at least some of the negative-polarity pulses in the bipolar pulse signal output by the pulse generating module 10 to be connected end to end to form a first pulse sequence; the frequency of the first pulse sequence is greater than the frequency threshold, so that the tissue to be ablated subjected to the first pulse sequence is heated.

[0074] Among them, the connection end to end between pulses can be understood as: the end moment of the current pulse and the start moment of the next pulse are the same moment, that is, there is no time interval between adjacent two pulses, so that the first pulse sequence is a continuous pulse sequence of positive and negative alternation; the current pulse can be a positive-polarity pulse or a negative-polarity pulse, and the next pulse can be a positive-polarity pulse and a negative-polarity pulse. Exemplarily, each pulse in the bipolar pulse signal is a pulse in the form of a square wave to achieve irreversible electroporation for the tissue to be ablated. The tissue to be ablated is, for example, abnormal tissue in a patient's lesion, such as a tumor. Among them, the frequency threshold can be determined according to the treatment target, and no specific limitation is made here. For example, the frequency threshold is determined according to the lower limit value of the target temperature range that the tissue to be ablated needs to reach during the treatment process. Then, it can be considered that when the frequency of the first pulse sequence is greater than the frequency threshold, the first pulse sequence can make the temperature of the tissue to be ablated reach the target temperature range. The duration of the first pulse sequence, the number of pulses in the sequence, and the parameters of each pulse (such as pulse width and amplitude, etc.) can all be set according to actual needs, and no limitation is made here. Exemplarily, the bipolar pulse signal can be applied to the tissue to be ablated through a treatment output device 30 in the ablation device. The treatment output device 30 is, for example, an electrode needle, which is used to extend into the tissue to be ablated to apply the bipolar pulse signal to the tissue to be ablated. For the convenience of description below, the frequency greater than the preset frequency is called high frequency, and the frequency less than the preset frequency is called low frequency.

[0075] In the embodiment of the present invention, the control module 20 controls the first pulse sequence in the bipolar pulse signal output by the pulse generation module 10 to be a high-frequency pulse sequence, and applies the bipolar pulse signal including the first pulse sequence to the tissue to be ablated, which is equivalent to applying electrical energy to the tissue to be ablated. Since there is no time interval between adjacent pulses in the first pulse sequence, the uninterrupted pulses can make the frequency of the first pulse sequence higher, which is beneficial to heat accumulation, increase the temperature of the tissue to be ablated, achieve the purpose of cryothermal effect, and expand the ablation range. At the same time, the thermal effect can also bring a hemostatic effect synchronously and prevent needle tract metastasis when the electrode needle is withdrawn. In summary, compared with the existing irreversible electroporation electrical pulse waveform that does not generate a thermal effect, the embodiment of the present invention can provide a bipolar pulse signal with a cryothermal effect, thereby expanding the ablation area.

[0076] The waveform of the first pulse sequence can be seen in Figure 2 , for example, the positive pulse in the first pulse sequence is the first positive pulse 41, and the negative pulse in the first pulse sequence is the first negative pulse 51. In the first pulse sequence, the first positive pulse 41 and the first negative pulse 51 can be staggered one by one. For example, the odd pulses are the first positive pulse 41 and the even pulses are the first negative pulse 51; or, the odd pulses are the first negative pulse 51 and the even pulses are the first positive pulse 41.

[0077] Such as Figure 2 , the first positive pulse 41 and the first negative pulse 51 can be pulses with equal pulse widths and amplitudes. Or, the pulse widths and / or amplitudes of the first positive pulse 41 and the first negative pulse 51 can be unequal. As shown in Figure 3 , when there are pulses with unequal amplitudes and pulse widths in the first pulse sequence, the amplitude of the pulse with a wider pulse width can be set smaller so that the energy of each pulse corresponds to the requirements of the treatment target, taking into account the effect of the thermal effect and the safety of the treatment. For example, the pulse width of the first positive pulse 41 can be set to be less than the pulse width of the first negative pulse 51, and the amplitude of the first positive pulse 41 can be set to be greater than the amplitude of the first negative pulse 51. It should be noted that the pulse amplitude in this article refers to the absolute value of the pulse voltage; for a positive pulse, its voltage is positive and the amplitude is the maximum value of the voltage; for a negative pulse, its voltage is negative and the amplitude is the absolute value of the minimum value of the voltage.

[0078] Based on the above embodiments, optionally, when the control module 20 controls the output of the pulse generation module 10, it can also control the bipolar pulse signal to include: a second pulse sequence; in the second pulse sequence, there is a time interval between every two adjacent pulses, that is, the second pulse sequence is a discrete pulse sequence. The frequency of the second pulse sequence is lower than the frequency threshold. Then, compared with the first pulse sequence, the second pulse sequence is a low-frequency pulse sequence. Such a setting enables the amplitude of the second pulse sequence to be set higher than that of the first pulse sequence, which is beneficial to improving the effect of irreversible electroporation, such as increasing the number of pores and the pore area. Then, by applying the first pulse sequence and the second pulse sequence to the tissue to be ablated at different times, the advantages of the above two pulse sequences can be combined. That is, the thermal effect of the first pulse sequence can be used to expand the ablation range, and the second pulse sequence can be used to ensure the ablation efficiency, thereby reliably improving the ablation effect. It should be noted that the amplitude of the pulse sequence can be considered as the amplitude of the pulse with the highest amplitude in the pulse sequence; the frequency of the pulse sequence can be considered as the number of pulses in the pulse sequence per unit time.

[0079] The following will give an exemplary description of the composition of the second pulse sequence in conjunction with Figures 4 - 6 ,

[0080] In one embodiment, optionally, the second pulse sequence includes at least one of a second positive polarity pulse 42 and a second negative polarity pulse 52; the amplitude of the second positive polarity pulse 42 is higher than that of the first positive polarity pulse 41, and the amplitude of the second negative polarity pulse 52 is higher than that of the first negative polarity pulse 51.

[0081] Furthermore, the second pulse sequence can also include at least one of a third positive polarity pulse 43 and a third negative polarity pulse 53; the amplitude of the third positive polarity pulse 43 is higher than that of the first positive polarity pulse 41, and the amplitude of the third negative polarity pulse 53 is higher than that of the first negative polarity pulse 51. Moreover, the third positive polarity pulse 43 is different from the second positive polarity pulse 42, for example, the pulse width and / or amplitude are different, and the third negative polarity pulse 53 is different from the second negative polarity pulse 52, for example, the pulse width and / or amplitude are different. Such a setting enables the second pulse sequence to combine the advantages of different types of pulses. Specifically, it can be set that among the second positive polarity pulse 42 and the third positive polarity pulse 43, the one with the smaller amplitude has a wider pulse width; and among the second negative polarity pulse 52 and the third negative polarity pulse 53, the one with the smaller amplitude has a wider pulse width to ensure the ablation effect and the safety of the ablation process.

[0082] Exemplarily, one of the second positive polarity pulse 42 and the third positive polarity pulse 43 can be set as a nanosecond pulse, and the other as a microsecond pulse; also, one of the second negative polarity pulse 52 and the third negative polarity pulse 53 can be set as a nanosecond pulse, and the other as a microsecond pulse. Among them, the pulse width of the nanosecond pulse is in the nanosecond level, the pulse width of the microsecond pulse is in the microsecond level, and the amplitude of the nanosecond pulse is higher than that of the microsecond pulse. Figures 4 - 6 Exemplarily, the second positive polarity pulse 42 and the second negative polarity pulse 52 are high-amplitude narrow pulses, such as nanosecond pulses; the third positive polarity pulse 43 and the third negative polarity pulse 53 are low-amplitude wide pulses, such as microsecond pulses. Correspondingly, the amplitude of the first positive polarity pulse 41 is less than the amplitude of the third positive polarity pulse 43, and the amplitude of the third positive polarity pulse 43 is less than the amplitude of the second positive polarity pulse 42; the pulse width of the third positive polarity pulse 43 is greater than the pulse width of the second positive polarity pulse 42. The amplitude of the first negative polarity pulse 51 is less than the amplitude of the third negative polarity pulse 53, and the amplitude of the third negative polarity pulse 53 is less than the amplitude of the second negative polarity pulse 52; the pulse width of the third negative polarity pulse 53 is greater than the pulse width of the second negative polarity pulse 52. The above settings are not intended to limit the present invention. The second pulse sequence can include one, two, three, or all of the second positive polarity pulse 42, the third positive polarity pulse 43, the second negative polarity pulse 52, and the third negative polarity pulse 53 in any combination, and the number of pulses in the second pulse sequence and the parameters of each pulse can be set according to actual needs.

[0083] Exemplarily, the second pulse sequence can include at least one of a plurality of second positive polarity pulses 42 and a plurality of second negative polarity pulses 52; one or more second negative polarity pulses 52 can be set at intervals of one or more second positive polarity pulses 42. As Figure 4 shown, the second pulse sequence can be set as a nanosecond pulse sequence, and the second positive polarity pulse 42 and the second negative polarity pulse 52 can also be staggered one by one.

[0084] Alternatively, the second pulse sequence can include at least one of a plurality of third positive polarity pulses 43 and a plurality of third negative polarity pulses 53; one or more third negative polarity pulses 53 can be set at intervals of one or more third positive polarity pulses 43. As Figure 5 shown, the second pulse sequence can be set as a microsecond pulse sequence, and the third positive polarity pulse 43 and the third negative polarity pulse 53 can also be staggered one by one.

[0085] Or, the second pulse sequence can include at least one of a plurality of second positive polarity pulses 42 and a plurality of second negative polarity pulses 52, and at least one of a plurality of third positive polarity pulses 43 and a plurality of third negative polarity pulses 53, forming a pulse sequence mixed with nanosecond and microsecond pulses; one or more microsecond pulses can be set at intervals of one or more pulses in nanosecond form. As Figure 6, multiple groups of second positive polarity pulses 42 and second negative polarity pulses 52 can be set, and are interleaved with multiple groups of third positive polarity pulses 43 and third negative polarity pulses 53 group by group.

[0086] Among the second positive polarity pulses 42, third positive polarity pulses 43, second negative polarity pulses 52 and third negative polarity pulses 53, pulses with high amplitude and narrow pulse width, such as nanosecond pulses, can punch more holes in the cell membrane during irreversible electroporation; pulses with low amplitude and wide pulse width, such as microsecond pulses, can expand the holes punched in the cell membrane to convert the holes into an irreversible state. Combining pulses with high amplitude and narrow pulse width and pulses with low amplitude and wide pulse width is beneficial to ensuring the electroporation efficiency and enhancing the ablation effect.

[0087] An exemplary description of the possible structure of the pulse generating device will be given below.

[0088] Continue to refer to Figure 1 , in one embodiment, optionally, the pulse generating module 10 includes: a first pulse generating circuit 110 and a second pulse generating circuit 120. The first pulse generating circuit 110 is connected to the control module 20 and is used to generate each positive polarity pulse in the bipolar pulse signal. The second pulse generating circuit 120 is connected to the control module 20 and is used to generate each negative polarity pulse in the bipolar pulse signal. By separately arranging the generating circuit of the positive polarity pulse and the generating circuit of the negative polarity pulse, the first pulse generating circuit 110 and the second pulse generating circuit 120 can adopt similar or the same structure, and adopt similar or the same control method. Only by changing the current flow direction, the control logic can be effectively simplified.

[0089] On the basis of the above embodiments, optionally, the first pulse generating circuit 110 may include: a first pulse generating sub-module 111, connected to the control module 20, for generating a first positive polarity pulse. The second pulse generating circuit 120 includes: a second pulse generating sub-module 121, connected to the control module 20, for generating a first negative polarity pulse. Based on the first pulse generating sub-module 111 and the second pulse generating sub-module 121, combined with the control of the control module 20, a first pulse sequence in the bipolar pulse signal can be generated. Specifically, the control module can control the first pulse generating sub-module 111 and the second pulse generating sub-module 112 to output alternately, so that multiple first positive polarity pulses and multiple first negative polarity pulses are connected end to end to form a first pulse sequence.

[0090] More specifically, the process of the control module 20 controlling the pulse generating module 10 to output the first pulse sequence may include:

[0091] The control pulse generation module 10 operates continuously for multiple pulse cycles. Among them, one pulse cycle includes: sending a first control signal to the first pulse generation sub-module 111 to control the first pulse generation sub-module 111 to output a first positive-polarity pulse; starting from the issuance of the first control signal, after a delay equal to the pulse width of the first positive-polarity pulse, sending a second control signal to the second pulse generation sub-module 121 to control the second pulse generation sub-module 121 to output a first negative-polarity pulse. Among them, starting from the issuance of the second control signal in the current pulse cycle, after a delay equal to the pulse width of the first negative-polarity pulse, the next pulse cycle is controlled to start. In this way, based on the control of the output time of each control signal, the time for different pulse generation sub-modules to release corresponding pulses can be controlled, so as to form a first pulse sequence in the form of Figure 2 or Figure 3 or other forms.

[0092] Figure 7 FIG. Figure 7 is a schematic structural diagram of another irreversible electroporation pulse generation device provided by an embodiment of the present invention. Refer to Figure 7 , on the basis of the above embodiments, optionally, the first pulse generation circuit may further include: a third pulse generation sub-module 112, the third pulse generation sub-module 112 is connected to the control module 20 and is used to generate a second positive-polarity pulse. And / or, the second pulse generation circuit 120 may further include: a fifth pulse generation sub-module 122; the fifth pulse generation sub-module 122 is connected to the control module 20 and is used to generate a second negative-polarity pulse.

[0093] Further, the first pulse generation circuit may further include: a fourth pulse generation sub-module 113; the fourth pulse generation sub-module 113 is connected to the control module 20 and is used to generate a third positive-polarity pulse. And / or, the second pulse generation circuit 120 may further include: a sixth pulse generation sub-module 123; the sixth pulse generation sub-module 123 is connected to the control module 20 and is used to generate a third negative-polarity pulse.

[0094] Based on the control of the output time of the control signals of at least one of the third pulse generation sub-module 112, the fourth pulse generation sub-module 113, the fifth pulse generation sub-module 122, and the sixth pulse generation sub-module 123 by the control module 20, the time for the pulse generation sub-module to release the corresponding pulse can be controlled, so as to form a second pulse sequence in the bipolar pulse signal. It should be noted that the number of pulse generation sub-modules listed here is not a limitation to the present invention. In other embodiments, when more types of pulses need to be generated, more corresponding pulse generation sub-modules can be equipped.

[0095] Preferably, it can be set that the pulse generation module 10 includes Figure 7All six pulse generation sub - modules therein are used to improve the diversity and configuration flexibility of the bipolar pulse signals output by the irreversible electroporation pulse generation device.

[0096] Based on the above - mentioned embodiments, optionally, different pulse generation sub - modules may adopt the same or similar structures. Here, the structure of one pulse generation sub - module (for example, the first pulse generation sub - module) will be taken as an example for illustration. The structures of other pulse generation sub - modules can refer to this structure and will not be elaborated further. Figure 8 It is a schematic structural diagram of a first pulse generation sub - module provided by an embodiment of the present invention. Refer to Figure 8 , exemplarily, the first pulse generation sub - module 111 may include a plurality of first pulse generation units 1111, and each first pulse generation unit 1111 is used to generate a first positive - polarity pulse. The power supply terminals of each first pulse generation unit 1111 are all connected to the first power supply unit 61. The output voltage of the first power supply unit 61 can, for example, determine the amplitude of each first positive - polarity pulse. The control terminals of each first pulse generation unit 1111 are all connected to the control module 20, and the control module 20 is used to control the time when each first pulse generation unit 1111 outputs the first positive - polarity pulse. The output terminals of each first pulse generation unit 1111 are all connected to the load corresponding to the first pulse generation sub - module 111, such as an electrode in an electrode needle, so as to apply the first positive - polarity pulse to the tissue to be ablated through the electrode in the electrode needle. The first pulse generation unit 1111 can adopt any existing pulse generation structure. For example, the first pulse generation unit 1111 can be a combined structure of a capacitor, a transistor, and a diode. The capacitor can store and release energy. The on - off of the transistor is used to control whether the first pulse generation unit 1111 outputs a pulse, and the diode controls the direction of the electrical signal.

[0097] Based on the above - mentioned embodiments, optionally, the irreversible electroporation pulse generation device may further include a power management module, which is respectively connected to the power supply system, the control module 20, and the pulse generation module 10. The power management module is used to convert the power supplied by the power supply system and supply power to the control module 20 and the pulse generation module 10. Specifically, the power management module may include an energy storage unit and a plurality of power supply units. The plurality of power supply units are respectively used to provide different power supply voltages. The plurality of power supply units include, for example, a plurality of high - voltage power supply units, which are used to output voltages to each pulse generation sub - module. Each high - voltage power supply unit includes, for example, the above - mentioned first power supply unit 61. Pulse generation sub - modules that output pulses with the same amplitude can be connected to the same power supply unit, and pulse generation sub - modules that output pulses with different amplitudes can be connected to different power supply units. In addition, the power management module may also include a low - voltage power supply unit for supplying power to the control module and other functional modules in the device, which will not be listed one by one here.

[0098] Based on the above embodiments, optionally, the irreversible electroporation pulse generating device may further include an output switching module to facilitate the output state switching function of multiple electrode needles. The output switching module is respectively connected to the control module 20 and the pulse generating module 10, and is connected to the treatment output device, such as each electrode needle in the ablation device. The output switching module is used to receive bipolar pulse signals and select the electrode needles that receive bipolar pulse signals according to the control of the control module 20.

[0099] Based on the above embodiments, optionally, the bipolar pulse signal is a square wave signal, and each pulse in the bipolar pulse signal is a square wave pulse. The parameters of the first pulse sequence can be set as follows: the amplitude of the first pulse sequence is between 0 - 1 kV; the amplitude of any pulse in the first pulse sequence can be between 0 - 1 kV. The frequency of the first pulse sequence is between 10 Hz - 5 MHz. The pulse width of any pulse in the first pulse sequence is between 100 ns - 10 μs.

[0100] The embodiment of the present invention also provides an ablation device, including the irreversible electroporation pulse generating device provided in any embodiment of the present invention, and having corresponding beneficial effects. Figure 9 is a schematic structural diagram of an ablation device provided by an embodiment of the present invention. Refer to Figure 9 , exemplarily, the ablation device includes an irreversible electroporation pulse generating device 1 for outputting bipolar pulse signals capable of achieving irreversible electroporation. Exemplarily, the treatment output device 30 of the ablation device may include multiple electrode needles, and the electrode needles can adopt any existing structure. For example, two unipolar electrode needles can be used to form a set of treatment devices, with one electrode provided in each electrode needle; or, one bipolar electrode needle can be used to form a treatment device, with two electrodes provided in each electrode needle.

[0101] Figure 10 is a schematic structural diagram of another ablation device provided by an embodiment of the present invention. Combining Figure 9 and Figure 10 , based on the above embodiments, optionally, the ablation device further includes a power supply system 70, connected to the power management module 60 in the irreversible electroporation pulse generating device 1, and connected to the power supply E. The power supply system 70 may include structures such as a power filter and an isolation transformer.

[0102] Based on the above embodiments, optionally, the ablation device may further include an output interface P1, and the output switching module 90 in the irreversible electroporation pulse generating device 1 can be connected to each electrode needle through the output interface P1.

[0103] Based on the above embodiments, optionally, the ablation device may further include a human-machine interaction module 80 and a connection control module 20 for providing various human-machine interaction functions. Exemplarily, the human-machine interaction module 80 may include a host computer 81, specifically including a host and a display, for visualizing the treatment process; the host computer 81 and the control module 20 may be communicatively connected via an optical fiber. In addition, the human-machine interaction module 80 may further include an emergency stop switch K1, a foot switch K2, and various signal line interfaces P2 respectively connected to the control module 20 to implement various control functions and signal interactions of the ablation device.

[0104] The embodiment of the present invention also provides a pulse control method, which is applied to the irreversible electroporation pulse generating device provided in any embodiment of the present invention and has corresponding beneficial effects. The pulse control method includes:

[0105] High-frequency output stage: The control module controls the pulse generation module to output at least one first pulse sequence.

[0106] Wherein, the frequency of the first pulse sequence is higher than the frequency threshold. By setting the high-frequency output stage, the high-frequency first pulse sequence is applied to the tissue to be ablated. Since the pulses in the first pulse sequence are continuous, it is beneficial to achieve heat accumulation and generate a thermal effect, so that the temperature of the tissue to be ablated rises, achieving the purpose of low-temperature thermal effect, realizing thermal ablation, and expanding the ablation range. Exemplarily, the tissue temperature can be controlled between 40°C and 60°C. With this setting, compared with the existing IRE electric pulse waveform that does not generate a thermal effect, the embodiment of the present invention can provide a bipolar pulse signal with a thermal effect, expanding the ablation area. At the same time, the thermal effect can also bring a hemostatic effect synchronously and prevent needle tract metastasis when the electrode needle is withdrawn. And, compared with the existing radiofrequency ablation, the first pulse sequence provided by the embodiment of the present invention is a square wave pulse sequence, and its electric field strength is much higher than that of radiofrequency, which is easy to achieve energy accumulation and temperature control.

[0107] Based on the above embodiments, optionally, it may be set that the pulse control method includes: a high-frequency mode, which only includes the above high-frequency output stage. In the high-frequency mode, the ablation device applies the bipolar pulse signal including at least one first pulse sequence output in the high-frequency output stage to the tissue to be ablated through the electrode needle.

[0108] Based on the above embodiments, in the high-frequency mode, there are various waveforms of the bipolar pulse signal. Several of them are described below, but they are not intended to limit the present invention. Figure 11 It is a waveform schematic diagram of a bipolar pulse signal in the high-frequency mode provided by the embodiment of the present invention. Refer to Figure 11, in one embodiment, optionally, when the amplitude of the first pulse sequence is lower than the voltage threshold, it can be set that only one first pulse sequence L1 is included in the high-frequency output stage TH. Wherein, the voltage threshold can be determined according to the safe voltage that can be continuously applied to the organism. By applying continuously uninterrupted positive and negative alternating pulses throughout the high-frequency output stage TH, good energy accumulation is achieved, and the pulse amplitude is lower than the voltage threshold, which can ensure treatment safety.

[0109] Figure 12 It is a waveform schematic diagram of a bipolar pulse signal in another high-frequency mode provided by an embodiment of the present invention. Refer to Figure 12 , in another embodiment, optionally, the amplitude of the first pulse sequence exceeds the voltage threshold, and at least two first pulse sequences are included in the high-frequency output stage TH, and there is a time interval between two adjacent first pulse sequences. Figure 12 Three first pulse sequences, namely L1-1, L1-2, and L1-3, are exemplarily given in . Exemplarily, the number of pulses in the first pulse sequence with an amplitude higher than the voltage threshold is less than the number of pulses in the first pulse sequence with an amplitude lower than the voltage threshold. In this embodiment, by intermittently providing multiple first pulse sequences with a relatively high amplitude throughout the high-frequency output stage TH, the thermal effect can also be achieved, and it can avoid electric injury to the human body caused by excessive continuous voltage.

[0110] It should be noted that Figure 11 and Figure 12 The waveform of the first pulse sequence in is only for exemplary illustration and is not a limitation to the present invention. The first pulse sequence in the high-frequency output stage TH can adopt the first pulse sequence provided by any embodiment of the present invention. Exemplarily, the first pulse sequence is a square wave pulse sequence, and its parameters can be set as follows: the amplitude of the first pulse sequence is between 0 - 1 kV; the amplitude of any pulse in the first pulse sequence can be between 0 - 1 kV. The frequency of the first pulse sequence is between 10 Hz - 5 MHz. The pulse width of any pulse in the first pulse sequence is between 100 ns - 10 μs.

[0111] On the basis of the above embodiments, optionally, the process of the control module controlling the pulse generation module to output the first pulse sequence includes: controlling the pulse generation module to continuously work for multiple pulse periods.

[0112] Each pulse period includes:

[0113] 1) Send a first control signal to the first pulse generation sub-module to control the first pulse generation sub-module to output a first positive-polarity pulse.

[0114] 2) After a delay equal to the pulse width of the first positive pulse from the issuance of the first control signal, a second control signal is issued to the second pulse generation sub-module to control the second pulse generation sub-module to output a first negative pulse.

[0115] Among them, from the issuance of the second control signal in the current pulse period, after a delay equal to the pulse width of the first negative pulse, the next pulse period is controlled to start until the first pulse sequence ends.

[0116] Based on the above embodiments, optionally, the pulse control method further includes:

[0117] Low-frequency output stage: The control module controls the pulse generation module to output at least one second pulse sequence; among them, the frequency of the first pulse sequence is greater than the frequency of the second pulse sequence, and the amplitude of the first pulse sequence is less than the amplitude of the second pulse sequence.

[0118] Among them, in the low-frequency output stage, the ablation device can apply a bipolar pulse signal including at least one second pulse sequence output in the low-frequency output stage to the tissue to be ablated through the electrode needle, which is equivalent to providing non-thermal ablation. By providing pulses with a large instantaneous power and a short action time, it is beneficial to achieve irreversible electroporation.

[0119] Among them, the second pulse sequence includes at least one of a second positive pulse, a second negative pulse, a third positive pulse, and a third negative pulse. Among them, one of the second positive pulse and the third positive pulse is a nanosecond pulse, and the other is a microsecond pulse; one of the second negative pulse and the third negative pulse is a nanosecond pulse, and the other is a microsecond pulse; the amplitude of any nanosecond pulse is greater than the amplitude of any microsecond pulse. Exemplarily, the second positive pulse and the second negative pulse are nanosecond pulses; the third positive pulse and the third negative pulse are microsecond pulses; the amplitude of any one of the second positive pulse and the second negative pulse is greater than the amplitude of any one of the third positive pulse and the third negative pulse. In practical applications, the second pulse sequence in the low-frequency output stage can adopt the second pulse sequence provided by any embodiment of the present invention, and the specific parameters can be configured according to actual needs.

[0120] Based on the above embodiments, optionally, it can be set that the pulse control method includes:

[0121] Collaborative mode: includes a high-frequency output stage and a low-frequency output stage that are performed in a time-sharing manner. In the collaborative mode, the ablation device applies a bipolar pulse signal containing at least one first pulse sequence output from the high-frequency output stage and a bipolar pulse signal containing at least one second pulse sequence output from the low-frequency output stage to the tissue to be ablated in a time-sharing manner through the electrode needle. Specifically, the control module can control the execution of the high-frequency mode or the collaborative mode by controlling the release of different pulse intervals; the control module can also control other pulse parameters, such as controlling the amplitude of each pulse by controlling the working process of the power management module.

[0122] On the basis of the above embodiments, in the cooperative mode, there are multiple waveforms of the bipolar pulse signal. Figures 13 - 17 , several of them are described here, but they are not intended to limit the present invention.

[0123] In one embodiment, optionally, in the collaborative mode, the low-frequency output stage TL may be controlled to be performed before the high-frequency output stage TH, for example Figure 13 By applying a high-frequency output phase TH after a low-frequency output phase TL, the electrode needle can be heated, thereby preventing needle track shift.

[0124] In another embodiment, optionally, in the collaborative mode, the high-frequency output stage TH may be controlled to be performed before the low-frequency output stage TL, for example Figures 14 - 17 As shown. With this arrangement, the ablation area can be expanded by thermal ablation in the high-frequency output stage TH, and then the ablation efficiency can be improved by non-thermal ablation in the low-frequency output stage TL, thereby achieving a better treatment effect. For example, as Figures 14 - 16 As shown, the low-frequency output stage TL can be set to include a second pulse sequence L2; or, as shown Figure 17 As shown, the low-frequency output stage TL can also be set to include multiple second pulse sequences L2, Figure 17 Two second pulse sequences, L2-1 and L2-2, are exemplarily shown. When the low-frequency output stage TL includes multiple second pulse sequences, at least two of the second pulse sequences may have different waveforms to balance the beneficial effects of each waveform. It should be noted that each second pulse sequence L2 may utilize any pulse combination.

[0125] In order to verify the effects of the pulse control methods provided in the embodiments of the present invention, the inventors conducted multiple control experiments using rabbit liver as the experimental subject, which are described in detail below. The reference control group is marked as group ①, and the experimental groups with different parameters are marked as groups ② to group Groups ② to ⑧ used the same type of electrode needles as group ①, which were pulmonary catheter needles, or non-water-cooled 5-5-5 (e.g., platinum-plated 5-5-5); Groups ⑨ to ⑨ Use a water-cooled needle 5-5-5. Among them, the water-cooled needle experimental groups all use the same rotation speed of the cooling water pump, for example, 200 r. For all experimental groups containing high-frequency pulses, the frequency of the high-frequency pulses is 180 kHz. For all experimental groups containing low-frequency pulses, the low-frequency pulses are applied in the following manner: 200 p (20 p / 5 s), that is, a total of 200 pulses are applied, and there is a 5-second pause every 20 pulses are applied.

[0126] The experimental conditions for each group can be seen in Table 1, and the explanations for each item in Table 1 are as follows: The high-frequency pulse can correspond to the pulse signal in the above high-frequency output stage, and the low-frequency pulse can correspond to the pulse signal in the above low-frequency output stage. In the low-frequency pulse type: A represents the relevant parameters of the nanosecond pulse, and the parameter units related to the pulse width and delay are both ns; B represents the relevant parameters of the microsecond pulse, and the parameter units related to the pulse width and delay are both μs. The number of positive / negative poles in the string represents how many positive / negative polarity pulses there are in the second pulse sequence. The positive-negative pulse delay represents the time interval between the end moment of the positive polarity pulse and the start moment of the next adjacent negative polarity pulse in the second pulse sequence; the negative-positive pulse delay represents the time interval between the end moment of the negative polarity pulse and the start moment of the next adjacent positive polarity pulse in the second pulse sequence. The pulse train delay represents the time interval between adjacent second pulse sequences. The high-frequency sequence indicates whether the high-frequency output stage is before or after.

[0127] Table 1

[0128]

[0129]

[0130] The experimental results can be seen in Figures 18 - 44 , where Figures 18 - 19 is the experimental result of Group ①, Figures 20 - 21 is the experimental result of Group ②, Figures 22 - 23 is the experimental result of Group ③, Figures 24 - 26 is the experimental result of Group ④, Figures 27 - 28 is the experimental result of Group ⑤, Figures 29 - 30 is the experimental result of Group ⑥, Figures 31 - 33 is the experimental result of Group ⑦, Figures 34 - 35 is the experimental result of Group ⑧, Figures 36 - 37 is the experimental result of Group ⑨, Figures 38 - 39 is the experimental result of Group ⑩, Figures 40 - 41 is the result of Group experimental result; Figures 42 - 44 are respectively the columnar result comparison charts of the ablation area (unit: cm 2 ), ablation length (unit: cm), and ablation width (unit: cm) of the results of each group except Group ②. And the results of each group are statistically presented in Table 2.

[0131] Table 2

[0132]

[0133] In addition, the inventor used an ex vivo porcine liver as the experimental object and conducted actual temperature measurements in multiple groups of control experiments. The temperature measurement results of some groups can be seen in Table 3. In Table 3, voltage - rotation speed represents the high - frequency pulse amplitude and the water pump rotation speed of each group (0r means using a non - water - cooled needle), and Tis represents the temperature at the i - th second of the temperature measurement time.

[0134] Table 3

[0135]

[0136] Analyzing the above results, it can be seen that the pulse control method provided by the embodiments of the present invention can effectively provide a thermal effect and expand the ablation area compared with the traditional method of only setting low - frequency pulses. It is preferably to adopt a cooperative mode and set the high - frequency output stage prior to the low - frequency output stage.

[0137] It should be understood that the various forms of the processes shown above can be reordered, steps can be added or deleted. For example, the steps described in the present invention can be executed in parallel, sequentially, or in a different order, as long as the desired results of the technical solution of the present invention can be achieved. No limitation is made herein.

[0138] The above - mentioned specific embodiments do not constitute a limitation to the protection scope of the present invention. Those skilled in the art should understand that various modifications, combinations, sub - combinations, and substitutions can be made according to design requirements and other factors. Any modifications, equivalent substitutions, and improvements made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. An irreversible electroporation pulse generating device, characterized in that, include: Pulse generation module; A control module is connected to the pulse generating module, and is used to control the pulse generating module to output a bipolar pulse signal, and to control the time interval between adjacent pulses in the bipolar pulse signal; wherein, the control module controls at least part of the positive polarity pulses and at least part of the negative polarity pulses in the bipolar pulse signal output by the pulse generating module to be connected end to end to form a first pulse sequence; the frequency of the first pulse sequence is greater than a frequency threshold, so that the temperature of the tissue to be ablated that is subjected to the first pulse sequence is increased.

2. The irreversible electroporation pulse generating device according to claim 1, wherein The pulse generating module comprises: a first pulse generating circuit, connected to the control module, and configured to generate the positive polarity pulses in the bipolar pulse signal; The second pulse generating circuit is connected to the control module and is used to generate the negative polarity pulses in the bipolar pulse signal.

3. The irreversible electroporation pulse generating device according to claim 2, characterized in that The first pulse sequence includes a plurality of first positive polarity pulses and a plurality of first negative polarity pulses; The first pulse generating circuit includes: a first pulse generating submodule, connected to the control module, and configured to generate the first positive polarity pulse; The second pulse generating circuit includes: a second pulse generating submodule, connected to the control module, and configured to generate the first negative polarity pulse; The control module is used to control the first pulse generating submodule and the second pulse generating submodule to output alternately, so that multiple first positive polarity pulses and multiple first negative polarity pulses are connected end to end to form the first pulse sequence.

4. The irreversible electroporation pulse generating device according to claim 3, characterized in that, The bipolar pulse signal further includes: a second pulse sequence; the second pulse sequence includes at least one of a second positive polarity pulse and a second negative polarity pulse; and in the second pulse sequence, there is a time interval between adjacent pulses; wherein the frequency of the second pulse sequence is less than the frequency threshold; The first pulse generating circuit further includes: a third pulse generating submodule; the third pulse generating submodule is connected to the control module and is used to generate the second positive polarity pulse; And / or, the second pulse generating circuit further includes: a fifth pulse generating submodule; the fifth pulse generating submodule is connected to the control module and is used to generate the second negative polarity pulse.

5. The irreversible electroporation pulse generating device according to claim 4, wherein, The second pulse sequence further includes at least one of a third positive polarity pulse and a third negative polarity pulse; wherein the pulse width and / or amplitude of the third positive polarity pulse is different from that of the second positive polarity pulse, and the pulse width and / or amplitude of the third negative polarity pulse is different from that of the second negative polarity pulse; The first pulse generating circuit further includes: a fourth pulse generating submodule; the fourth pulse generating submodule is connected to the control module and is used to generate the third positive polarity pulse; And / or, the second pulse generating circuit further includes: a sixth pulse generating submodule; the sixth pulse generating submodule is connected to the control module and is used to generate the third negative polarity pulse.

6. The irreversible electroporation pulse generating device according to claim 5, wherein The amplitude of the first positive polarity pulse is smaller than the amplitude of the second positive polarity pulse, and smaller than the amplitude of the third positive polarity pulse; Between the second positive polarity pulse and the third positive polarity pulse, the one with a smaller amplitude has a wider pulse width; The amplitude of the first negative-polarity pulse is less than that of the second negative-polarity pulse and less than that of the third negative-polarity pulse; Among the second negative-polarity pulse and the third negative-polarity pulse, the pulse width of the one with the smaller amplitude is wider.

7. The irreversible electroporation pulse generating device according to any one of claims 1-6, characterized in that, Further included: A power management module, which is respectively connected to the power supply system, the control module and the pulse generation module; The power management module is used to convert the power supplied by the power supply system and supply power to the control module and the pulse generation module; And / or, An output switching module, which is respectively connected to the control module and the pulse generation module, and is connected to each electrode needle in the ablation device; the output switching module is used to receive the bipolar pulse signal and select the electrode needle for receiving the bipolar pulse signal according to the control of the control module.

8. The irreversible electroporation pulse generating device according to any one of claims 1-6, characterized in that, The bipolar pulse signal is a square wave signal; And / or, the amplitude of the first pulse sequence is between 0 - 1 kV; And / or, the frequency of the first pulse sequence is between 10 Hz - 5 MHz; And / or, the pulse width of any pulse in the first pulse sequence is between 100 ns - 10 μs.

9. An ablation device, characterized in that, Including: The irreversible electroporation pulse generation device according to any one of claims 1 - 8.

10. The ablation device according to claim 9, wherein, Further included: A power supply system, which is connected to the power management module in the irreversible electroporation pulse generation device; And / or, an output interface and a plurality of electrode needles, and the output switching module in the irreversible electroporation pulse generation device is connected to each of the electrode needles through the output interface; And / or, a human-machine interaction module, which is connected to the control module.

11. A pulse control method, characterized in that, Applied to the irreversible electroporation pulse generation device according to any one of claims 1 - 8, the pulse control method includes: High-frequency output stage: The control module controls the pulse generation module to output at least one first pulse sequence.

12. The pulse control method according to claim 11, wherein The pulse generation module includes a first pulse generation sub-module and a second pulse generation sub-module; The process of the control module controlling the pulse generation module to output the first pulse sequence includes: Controlling the pulse generation module to continuously work for a plurality of pulse periods; the pulse period includes: Sending a first control signal to the first pulse generation sub-module to control the first pulse generation sub-module to output a first positive-polarity pulse; After a delay equal to the pulse width of the first positive-polarity pulse from the sending of the first control signal, sending a second control signal to the second pulse generation sub-module to control the second pulse generation sub-module to output a first negative-polarity pulse; Wherein, after a delay equal to the pulse width of the first negative-polarity pulse from the sending of the second control signal in the current pulse period, controlling the start of the next pulse period.

13. The pulse control method according to claim 11, wherein, The amplitude of the first pulse sequence is lower than the voltage threshold, and one first pulse sequence is included in the high-frequency output stage; Or, The amplitude of the first pulse sequence exceeds the voltage threshold, and at least two first pulse sequences are included in the high-frequency output stage, and there is a time interval between adjacent two first pulse sequences.

14. The pulse control method according to claim 11, wherein Further included: Low-frequency output stage: the control module controls the pulse generation module to output at least one second pulse sequence; The frequency of the first pulse sequence is greater than the frequency of the second pulse sequence.

15. The pulse control method according to claim 14, wherein The second pulse sequence includes at least one of a second positive polarity pulse, a second negative polarity pulse, a third positive polarity pulse and the third negative polarity pulse; Among them, one of the second positive polarity pulse and the third positive polarity pulse is a nanosecond pulse, and the other is a microsecond pulse; one of the second negative polarity pulse and the third negative polarity pulse is a nanosecond pulse, and the other is a microsecond pulse; the amplitude of any of the nanosecond pulses is greater than the amplitude of any of the microsecond pulses.

16. The pulse control method according to claim 14, characterized in that, include: A high frequency mode, comprising the high frequency output stage; and / or, The collaborative mode includes the high-frequency output stage and the low-frequency output stage performed in a time-sharing manner.

17. The pulse control method according to claim 16, wherein When the pulse control method includes the cooperative mode, in the cooperative mode, the high-frequency output stage is performed before the low-frequency output stage.

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