CN114366280B

CN114366280B - Pulse processing device, pulse processing method, electronic apparatus, and storage medium

Info

Publication number: CN114366280B
Application number: CN202210279307.4A
Authority: CN
Inventors: 罗中宝; 赵宇; 张朕华
Original assignee: Shanghai Remedicine Co ltd
Current assignee: Shanghai Ruidao Medical Technology Co ltd
Priority date: 2022-03-22
Filing date: 2022-03-22
Publication date: 2022-11-08
Anticipated expiration: 2042-03-22
Also published as: CN114366280A

Abstract

A pulse processing apparatus, a pulse processing method, an electronic device, and a computer-readable storage medium. The pulse processing device comprises a first pulse module for providing a first pulse, a second pulse module for providing a second pulse, an output end and a controller, wherein the output end receives and outputs the first pulse and the second pulse; the controller controls the first pulse module to output first pulses to the output end in the hole opening stage, and controls the second pulse module to output second pulses to the output end in the hole expanding stage. The first pulse and the second pulse are used for irreversible electroporation ablation of target tissue cells, the first pulse has a first waveform for forming an opening in the target tissue cells, the second pulse has a second waveform for enlarging an aperture of the opening, and a low frequency component of the second waveform is less than that of the first waveform or the second waveform does not contain a low frequency component. The pulse processing device can eliminate or reduce the stimulation of the low-frequency component to the muscle.

Description

Pulse processing device, pulse processing method, electronic apparatus, and storage medium

Technical Field

Embodiments of the present disclosure relate to a pulse processing apparatus, a pulse processing method, an electronic device, and a computer-readable storage medium.

Background

Irreversible electroporation is a novel cell tissue ablation method, uses high-voltage electric pulses to generate irreversible nanometer-sized micropores on the surface of a cell membrane, thereby causing necrosis or apoptosis of cells, and can be used for ablation of tumors or benign hyperplastic tissues.

Disclosure of Invention

At least one embodiment of the present disclosure provides a pulse processing apparatus including a first pulse module configured to provide a first pulse, a second pulse module, an output, and a controller; the second pulse module is configured to provide a second pulse; the output end is configured to receive the first pulse and output the first pulse and receive the second pulse and output the second pulse; the controller is configured to control the first pulse module to output the first pulse to the output during a trepanning phase and control the second pulse module to output the second pulse to the output during a reaming phase. The first pulse and the second pulse are used for irreversible electroporation ablation of target tissue cells, the first pulse has a first waveform for forming an opening in the target tissue cells, the second pulse has a second waveform for enlarging the aperture of the opening, a low frequency component of the second waveform is less than the first waveform or the second waveform does not include a low frequency component, the low frequency component is a component having a frequency lower than a preset frequency threshold in a frequency domain.

For example, in a pulse processing apparatus provided by an embodiment of the present disclosure, the first waveform includes a square wave or a square wave, and the second waveform includes a sine wave.

For example, in a pulse processing apparatus provided in an embodiment of the present disclosure, a pulse frequency of the second pulse is in a range of 25kHz to 200 kHz.

For example, in a pulse processing apparatus provided in an embodiment of the present disclosure, a pulse frequency of the second pulse is in a range of 40kHz to 50kHz.

For example, in a pulse processing apparatus provided in an embodiment of the present disclosure, the controller is configured to: and controlling the first pulse and the second pulse to be output according to a preset sequence.

For example, in the pulse processing apparatus provided by an embodiment of the present disclosure, the amplitude of the first pulse is between-10 kV and +10kV, and the amplitude of the second pulse is between-10 kV and +10 kV.

For example, in a pulse processing apparatus provided in an embodiment of the present disclosure, the controller is further configured to: sending a first control instruction to the first pulse module to cause the first pulse module to output the first pulse to the output end during the trepanning phase, and sending a second control instruction to the second pulse module to cause the second pulse module to output the second pulse to the output end during the reaming phase.

For example, in a pulse processing apparatus provided in an embodiment of the present disclosure, the first pulse module is further configured to: generating a first initial pulse comprising a square wave and transforming the first initial pulse into the first pulse; the second pulse module is further configured to: generating a second initial pulse comprising a square wave and transforming the second initial pulse into the second pulse. The second initial pulse comprises a square wave having waveform parameters different from those of the first initial pulse.

For example, in the pulse processing apparatus provided in an embodiment of the present disclosure, the second pulse module includes an operational amplifier and an integrating circuit, the operational amplifier is configured to perform operational amplification processing on the second initial pulse, and convert a square wave in the second initial pulse into a triangular wave; an integration circuit is configured to transform the triangular wave into a sine wave comprised by the second pulse.

For example, in a pulse processing apparatus provided in an embodiment of the present disclosure, the second pulse module is further configured to: a third initial pulse comprising a sine wave is generated and modulated into the second pulse.

For example, in a pulse processing apparatus provided by an embodiment of the present disclosure, the second pulse includes a plurality of groups of sine waves, each group of sine waves includes at least one cycle of sine waves, each group of sine waves is spaced apart by a predetermined time period, and no pulse is provided within the predetermined time period.

For example, in a pulse processing apparatus provided in an embodiment of the present disclosure, the controller is further configured to: acquiring a first time period corresponding to the hole opening stage and a second time period corresponding to the hole expanding stage; controlling the first pulse module to output the first pulse to the output end in the first time period; and controlling the second pulse module to output the second pulse to the output end in the second time period.

At least one embodiment of the present disclosure provides a pulse processing method, including: providing and outputting a first pulse to be applied to the target tissue cells during the aperturing phase; providing and outputting a second pulse to be applied to the target tissue cells during the reaming stage; the first pulse and the second pulse are used for irreversible electroporation ablation of the target tissue cell, the first pulse has a first waveform for forming an opening in the target tissue cell, the second pulse has a second waveform for enlarging an aperture of the opening, a low frequency component of the second waveform is less than the first waveform or the second waveform does not include a low frequency component, the low frequency component is a component having a frequency lower than a preset frequency threshold in a frequency domain.

For example, in a pulse processing method provided by an embodiment of the present disclosure, the first waveform includes a rectangular wave or a square wave, and the second waveform includes a sine wave.

For example, in a pulse processing method provided by an embodiment of the present disclosure, a pulse frequency of the second pulse is in a range of 25kHz to 200 kHz.

For example, in a pulse processing method provided by an embodiment of the present disclosure, a pulse frequency of the second pulse is in a range of 40kHz to 50kHz.

For example, in a pulse processing method provided in an embodiment of the present disclosure, the method further includes: and controlling the first pulse and the second pulse to be output according to a preset sequence.

For example, in the pulse processing method provided by an embodiment of the present disclosure, the amplitude of the first pulse is between-10 kV and +10kV, and the amplitude of the second pulse is between-10 kV and +10 kV.

For example, in a pulse processing method provided by an embodiment of the present disclosure, providing and outputting a first pulse to be applied to a target tissue cell in an open pore stage includes: and sending a first control instruction to a first pulse module to enable the first pulse module to output the first pulse to an output end in the hole opening stage. Providing and outputting a second pulse to be applied to the target tissue cells during the reaming phase, comprising: and sending a second control instruction to a second pulse module to enable the second pulse module to output the second pulse to the output end in the reaming stage.

For example, in a pulse processing method provided by an embodiment of the present disclosure, providing and outputting a first pulse to be applied to a target tissue cell in an open pore stage includes: a first initial pulse comprising a square wave is generated and transformed into the first pulse. Providing and outputting a second pulse to be applied to the target tissue cells during the reaming stage, comprising: generating a second initial pulse comprising a square wave and transforming the second initial pulse into the second pulse, the second initial pulse comprising a square wave having waveform parameters different from those of the first initial pulse.

For example, in a pulse processing method provided by an embodiment of the present disclosure, transforming the second initial pulse into the second pulse includes: performing operational amplification processing on the second initial pulse, and converting a square wave in the second initial pulse into a triangular wave; the triangular wave is transformed into a sine wave comprised by the second pulse.

For example, in a pulse processing method provided by an embodiment of the present disclosure, providing and outputting a second pulse to be applied to the target tissue cell in a reaming stage includes: a third initial pulse comprising a sine wave is generated and modulated into the second pulse.

For example, in a pulse processing method provided by an embodiment of the present disclosure, the second pulse includes a plurality of groups of sine waves, each group of sine waves includes at least one cycle of sine waves, each group of sine waves is spaced by a predetermined time length, and no pulse is provided within the predetermined time length.

For example, an embodiment of the present disclosure provides a pulse processing method, further including: and acquiring a first time period corresponding to the hole opening stage and a second time period corresponding to the hole expanding stage. Providing and outputting a first pulse to be applied to cells of the target tissue during the aperturing phase, comprising: and controlling the first pulse module to output the first pulse to the output end in the first time period. Providing and outputting a second pulse to be applied to the target tissue cells during the reaming stage, comprising: and controlling the second pulse module to output the second pulse to the output end in the second time period.

At least one embodiment of the present disclosure provides an electronic device comprising a processor; a memory including one or more computer program modules; wherein the one or more computer program modules are stored in the memory and configured to be executed by the processor, the one or more computer program modules comprising instructions for implementing a pulse processing method provided by any embodiment of the present disclosure.

At least one embodiment of the present disclosure provides a computer-readable storage medium for storing non-transitory computer-readable instructions that, when executed by a computer, may implement a pulse processing method provided by any embodiment of the present disclosure.

Drawings

To more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings of the embodiments will be briefly introduced below, and it is apparent that the drawings in the following description relate only to some embodiments of the present disclosure and are not limiting to the present disclosure.

Fig. 1 is a schematic diagram of a pulse processing apparatus according to at least one embodiment of the present disclosure;

FIG. 2 is a schematic diagram illustrating a variation curve of pore radius under square wave pulse action provided by at least one embodiment of the present disclosure;

FIG. 3 is a schematic diagram illustrating a variation curve of pore radius under a sine wave pulse according to at least one embodiment of the present disclosure;

FIG. 4 illustrates a schematic diagram of a second pulse provided by at least one embodiment of the present disclosure;

FIG. 5 shows a schematic diagram of muscle contraction acceleration signals under the action of pulses of different frequencies;

fig. 6 is a schematic diagram of another pulse processing apparatus provided in at least one embodiment of the present disclosure;

fig. 7 is a schematic diagram of another pulse processing apparatus provided in at least one embodiment of the present disclosure;

fig. 8 illustrates a flow chart of a pulse processing method provided by at least one embodiment of the present disclosure;

fig. 9 is a schematic block diagram of an electronic device provided by some embodiments of the present disclosure;

fig. 10 is a schematic block diagram of another electronic device provided by some embodiments of the present disclosure; and

fig. 11 illustrates a schematic diagram of a computer-readable storage medium provided by at least one embodiment of the present disclosure.

Detailed Description

To make the objects, technical solutions and advantages of the embodiments of the present disclosure more apparent, the technical solutions of the embodiments of the present disclosure will be clearly and completely described below with reference to the drawings of the embodiments of the present disclosure. It is to be understood that the described embodiments are only a few embodiments of the present disclosure, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the disclosure without any inventive step, are within the scope of protection of the disclosure.

Unless otherwise defined, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this disclosure belongs. The use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another. Also, the use of the terms "a," "an," or "the" and similar referents do not denote a limitation of quantity, but rather denote the presence of at least one. The word "comprising" or "comprises", and the like, means that the element or item listed before the word covers the element or item listed after the word and its equivalents, but does not exclude other elements or items. The terms "connected" or "coupled" and the like are not restricted to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "upper", "lower", "left", "right", and the like are used only to indicate relative positional relationships, and when the absolute position of the object being described is changed, the relative positional relationships may also be changed accordingly.

The inventors have found that irreversible electroporation can comprise two stages. The first stage allows the transmembrane voltage to reach or exceed a threshold under high voltage, thereby creating small hydrophilic nanopores in the cell membrane. And in the second stage, under the action of the electric field force generated by the high-voltage pulse, the small hydrophilic nano-pores are subjected to size expansion, and after the size of the hydrophilic nano-pores exceeds a certain critical value, the size of the hydrophilic nano-pores still can be spontaneously expanded after the electric field is removed, so that irreversible opening is formed, and cells are ablated. The pulse width has a greater effect on the expansion process of the nanopore in the second stage than in the first stage. The second phase may for example use square wave pulses with a pulse width in the interval 50 mus-100 mus. In order to improve the reaming efficiency, in one embodiment, a pulse with a higher voltage and a narrower pulse width may be used for opening the pores in the first stage and a pulse with a lower voltage and a wider pulse width may be used for reaming in the second stage, which may effectively achieve opening of the cell membrane and pore size expansion.

However, the inventors have further investigated that the use of square wave pulses in the second stage has some disadvantages: because of the wide pulse width used during the reaming phase, the waveform contains a large amount of low frequency components, and low frequency stimulation causes strong muscle contractions, which require a large amount of muscle relaxant for relief. For example, a square wave is formed by superimposing a series of sine waves of different frequencies, including a low-frequency sine wave as a low-frequency component of the square wave, which may cause the above disadvantages. In addition, the square wave with wide pulse width can generate strong electrolytic water effect, thereby causing a large amount of bubbles on the surface of the electrode and increasing the risk of inducing thrombus.

At least one embodiment of the present disclosure provides a pulse processing apparatus, a pulse processing method, an electronic device, and a computer-readable storage medium. The pulse processing apparatus includes a first pulse module configured to provide a first pulse, a second pulse module, an output, and a controller; the second pulse module is configured to provide a second pulse; the output end is configured to receive and output the first pulse and receive and output the second pulse; the controller is configured to control the first pulse module to output a first pulse to the output during the trepanning phase and to control the second pulse module to output a second pulse to the output during the reaming phase. The first pulse and the second pulse are used for irreversible electroporation ablation of target tissue cells, the first pulse has a first waveform for forming an open pore on the target tissue cells, the second pulse has a second waveform for enlarging the aperture of the open pore, the low frequency component of the second waveform is less than that of the first waveform or the second waveform does not contain the low frequency component, and the low frequency component is a component with a frequency lower than a preset frequency threshold in a frequency domain.

The pulse processing device can eliminate or weaken the stimulation of the low-frequency component to the muscle by a mode of making the low-frequency component of the second waveform not contain the low-frequency component or making the low-frequency component of the second waveform less than the low-frequency component of the first waveform, and further can avoid strong muscle contraction.

Fig. 1 shows a schematic diagram of a pulse processing apparatus according to at least one embodiment of the present disclosure.

As shown in fig. 1, the pulse processing apparatus 100 may include a first pulse module 110, a second pulse module 120, an output 130, and a controller 140. The first pulse module 110 is configured to provide a first pulse. The second pulse module 120 is configured to provide a second pulse. The output 130 is configured to receive and output the first pulse and to receive and output the second pulse. The controller 140 is configured to control the first pulse module 110 to output a first pulse to the output 130 during the trepanning phase and the second pulse module 120 to output a second pulse to the output 130 during the reaming phase.

For example, the first pulse and the second pulse may each be a voltage pulse.

For example, the controller 140 may be in communication connection with an upper computer to receive a control instruction sent by the upper computer. For example, the upper computer may be configured to set parameters such as a voltage value, a pulse width, and a number of pulses of the pulse, and may send an instruction including the parameters to the controller 140, and the controller controls the components such as the first pulse module 110 and the second pulse module 120 to execute the instruction.

For example, the controller 140 may be configured to: sending a first control command to the first pulse module 110 causes the first pulse module 110 to output a first pulse to the output 130 during the tapping phase. For example, the controller 140 may send a first control instruction to the first pulse module 110 at the beginning of the tapping phase, and control the first pulse module 110 to output the first pulse to the output terminal 130 continuously or intermittently. At the end of the tapping phase, the controller 140 may send a stop instruction to the first pulse module 110 to control the first pulse module 110 to stop outputting the first pulse to the output 130.

For example, the controller 140 may also be configured to: sending a second control command to second pulse module 120 causes second pulse module 120 to output a second pulse to output 130 during the reaming phase. For example, the controller 140 may send a second control command to the second pulse module 120 at the beginning of the reaming phase, and control the second pulse module 120 to output a second pulse to the output 130 continuously or intermittently. At the end of the reaming phase, the controller 140 may send a stop command to the second pulse module 120 to control the second pulse module 120 to stop outputting the second pulse to the output 130.

For example, during the opening stage, the controller 140 controls the output terminal 130 to receive the first pulse output by the first pulse module 110 and output the first pulse to the electrode needle unit, so that the first pulse is applied to the target tissue cell through the electrode needle unit. During the reaming stage, the controller 140 controls the output terminal 130 to receive the second pulse output by the second pulse module 120 and output the second pulse to the electrode needle unit, so that the second pulse is applied to the target tissue cells through the electrode needle unit. For example, the output 130 may be implemented as a switching element that can switch the first pulse or the second pulse of the output.

For example, a first pulse having a first waveform for forming an opening in a target tissue cell and a second pulse having a second waveform for enlarging an aperture of the opening are used for irreversible electroporation ablation of the target tissue cell, the second waveform having a lower frequency content less than the first waveform or the second waveform containing no lower frequency content.

For example, the low frequency component is a component whose frequency is lower than a preset frequency threshold in the frequency domain. For example, the preset frequency threshold may be less than or equal to 10 kHZ. The preset frequency threshold may be determined according to actual situations, and the embodiment of the present disclosure does not limit this.

For example, a first pulse is used to form an opening (e.g., a hydrophilic nanopore) in a target tissue cell during an opening stage. And in the reaming stage, the aperture of the opening is enlarged by using the second pulse, and irreversible perforation can be formed under the condition that the opening is expanded to a certain degree, so that the purpose of ablating target tissue cells can be achieved.

For example, most periodic waveforms, except sine waves, are formed by superimposing a series of sine waves of different frequencies, such as square waves, rectangular waves, triangular waves, and the like. Therefore, the frequency components of these waveforms, such as square waves and rectangular waves, are complicated, and there are a variety of frequency components. The frequency component of the sine wave is relatively simple, and only one frequency component exists.

For example, the first waveform may comprise a rectangular or square wave, and in some embodiments may be a short pulse (e.g., pulse width of 1 μ s-10 μ s) square wave, for example, and during the opening phase, when an applied electric field is applied to the target tissue cells, the cell membrane is charged due to its insulating properties, and charges are accumulated on both sides of the cell membrane, with the rate of charge accumulation depending on the time constant of the cell membrane. Usually, the time constant of the cell membrane does not exceed 1 μ s (microsecond), i.e., the charge accumulation on both sides of the cell membrane reaches equilibrium around 1 μ s, and the transmembrane voltage of the cell membrane reaches a maximum. Also, the cell membrane opening process occurs in a short time, and the opening occurrence probability depends on the transmembrane voltage. Thus, applying short square-wave pulses can effectively achieve cell membrane opening. Meanwhile, because the pulse width is short, the low-frequency component is less, and the stimulation to the muscle is weaker. And does not generate strong water electrolysis effect.

For example, in some examples, the second waveform may include a sine wave. Since the sine wave has only one frequency component, the set frequency of the sine wave is the frequency component of the sine wave. For example, if the frequency of the second waveform is set to 25kHZ, the frequency component of the sine wave is only 25kHZ, and no other frequency component is present. Therefore, in this case, if the sine wave is set to a frequency greater than the preset frequency threshold, the sine wave does not include a low frequency component. In the case where the second pulse does not contain a low frequency component, the stimulation of the muscle by the low frequency component can be eliminated, and the generation of strong muscle contraction can be avoided. In addition, compared with square wave pulse, the sine wave pulse has fast positive and negative polarity switching, so that one kind of electrochemical reaction on the electrode is not caused to be continuously carried out, and the water electrolysis effect can be reduced.

For example, in other examples, the second waveform may be other than a sine wave, such as by filtering to reduce low frequency components of the second waveform so that the low frequency components of the second waveform are less than the low frequency components of the first waveform. In the case where the second pulse contains a small amount of low-frequency components, the stimulation of the low-frequency components to the muscle can be reduced, and thus, the generation of strong muscle contraction can be avoided.

The pulse processing device according to the embodiment of the present disclosure can eliminate or reduce the stimulation of the muscle by the low frequency component by making the second waveform contain no low frequency component or making the low frequency component of the second waveform less than the low frequency component of the first waveform, and thus can avoid strong muscle contraction. In addition, when the second waveform is a sine wave waveform, the effect of water electrolysis can be reduced.

For example, the process of cell pore size change can be expressed by the following equation:

U=k*(f_e+l*r ^-5 –2πγ+2πσr)

wherein U represents the speed of change of the aperture size; r represents the pore size; k is a coefficient determined by temperature and the diffusion speed of phospholipid bilayer; the first term f _ e on the right side of the formula is the acting force of an electric field, is determined by transmembrane voltage, aperture size and the like, and can be obtained by Maxwell stress tensor calculation; second term l r ^-5 Is the steric exclusion effect of the phospholipid group, l is the coefficient; the third item-2 pi gamma is the acting force acting on the hole edge, and gamma is the hole edge tension; the fourth term 2 π σ r is the surface force of the cell membrane, σ is the surface tension. Wherein, the first term f _ e and the second term l r ^-5 And the fourth term, the action of 2 π σ r forces, causes an expansion of the cell pore size, while the third term, the action of-2 π γ forces, causes a reduction of the cell pore size. In the absence of an applied electric field, the latter three forces maintain the cell pore size at a small equilibrium value (< 1 nm). When a sufficiently strong electric field is applied, the cell pore size begins to expand, at which point there is a critical value of pore size. If the aperture of the cell does not reach the critical value in the process of applying the electric field, the aperture can recover to the initial equilibrium value under the action of the last three forces after the action of the electric field is removed, and the reversible electroporation is obtained. If the pore size reaches this critical value during the application of the electric field, the pore size will spontaneously expand under the latter three forces, forming irreversible electroporation, even after the electric field is removed.

Fig. 2 is a schematic diagram illustrating a change curve of pore radius under square wave pulse according to at least one embodiment of the present disclosure.

As shown in fig. 2, the pulse width of the square wave pulse is set to, for example, 100 μ s, and when the electric field strength is E =458V/cm, the pore radius is not substantially changed, and irreversible electroporation cannot be achieved. When the electric field strength is increased to E =469V/cm, the change curve of the pore radius after the electric field is applied for a period of time tends to be upward, that is, the pore radius starts to increase, and the pore radius continues to increase in a later period of time, so that irreversible electroporation can be realized at such an electric field strength. When the electric field strength is increased to E =548V/cm, a tendency of an increase in the pore radius may occur in a shorter time and the rate of increase in the pore radius is faster, and thus irreversible electroporation may be more rapidly achieved.

Fig. 3 is a schematic diagram illustrating a variation curve of a pore radius under a sine wave pulse according to at least one embodiment of the present disclosure.

As shown in fig. 3, the pulse width of the sine wave pulse is also set to 100 μ s, for example, and the frequency is set to 50kHz, for example. When the electric field strength is E =548V/cm, the pore radius is oscillated for a period of time and then returns to the initial radius, and irreversible electroporation cannot be realized. When the electric field strength is increased to E =557V/cm, the aperture radius starts to increase under the action of the electric field and keeps increasing trend all the time, so that irreversible electroporation can be realized at the electric field strength. Irreversible electroporation can be achieved more rapidly as the electric field strength increases to E = 632V/cm. Therefore, it can be seen that the sine wave pulse enables irreversible electroporation, and the threshold of electric field intensity required for the sine wave to achieve irreversible electroporation is higher than that of the square wave pulse to achieve irreversible electroporation.

For example, the reaming process mainly depends on the electric field force applied to the hole wall, and the electric field force is calculated according to maxwell stress tensor, and the electric field force is proportional to the square of the electric field, so that the electric field force can be generated by alternating current pulses (such as sine wave pulses) with alternating polarities, and the alternating current does not generate strong electrolytic water effect. And, compared with the square wave pulse, the sine wave pulse can make the voltage rise to a higher value, because if the square wave pulse with wider pulse width is adopted in the hole expanding stage, a stronger electrolyzed water effect can be generated when the voltage rises, and after the sine wave pulse is adopted, because the quick switching of the positive and negative polarities of the sine wave can not cause the continuous proceeding of an electrochemical reaction on the electrode, so when the voltage rises, the electrolyzed water effect is weaker, therefore, after the sine wave pulse is adopted, the voltage can be allowed to rise to a higher value.

In some embodiments below, the pulse processing apparatus of the embodiments of the present disclosure is explained and illustrated by taking the example that the first pulse uses a square wave pulse and the second pulse uses a sine wave pulse.

Fig. 4 illustrates a schematic diagram of a second pulse provided by at least one embodiment of the present disclosure.

As shown in FIG. 4, for example, the second pulse includes a plurality of sets of sinusoids, each set including at least one cycle of sinusoids, each set spaced apart by a predetermined length of time, within which no pulse is provided. For example, a set of sine waves may comprise a number of cycles of a sine wave waveform, such as a sine wave waveform comprising five cycles. Each set of sinusoids is separated by a period of time during which no pulses are provided, which may be referred to as a dead time. That is, a period of sine wave pulse is applied for a period of dead time, and then a period of sine wave pulse is applied for a period of dead time, and the cycle is repeated until the reaming stage is finished. In this manner, the slight amount of heat generated during the ablation process may be reduced.

For example, the controller is configured to: and controlling the first pulse and the second pulse to be output according to a preset sequence. For example, the control output 130 outputs a first pulse to form a desired opening in the target tissue cells, and then the control output 130 outputs a second pulse until the opening is irreversibly dilated. For example, the pulsing process includes two stages, with a prior opening stage providing only the first pulse until the opening is complete; the subsequent reaming stage provides only the second pulse until reaming is complete without the need to repeatedly apply the first and second pulses.

For example, the controller is further configured to: acquiring a first time period corresponding to the hole opening stage and a second time period corresponding to the hole expanding stage; in a first time period, controlling a first pulse module to output a first pulse to an output end; and controlling the second pulse module to output the second pulse to the output end in the second time period. For example, a first time period required by the hole opening stage, that is, a period of time beginning from the starting time of the hole opening stage and having a first time period, and a second time period required by the hole expanding stage, that is, a period of time beginning from the starting time of the hole expanding stage and having a second time period may be preset. The end time of the first time period is earlier than the start time of the second time period.

Figure 5 shows a diagram of the muscle contraction acceleration signal under the action of pulses of different frequencies.

As shown in fig. 5, the muscle contraction effect is reduced as the frequency increases, so that the high frequency alternating current can effectively eliminate the muscle contraction. For example, in some examples, the pulse frequency of the second pulse may be in the range of 25kHz-200kHz to attenuate or eliminate muscle contraction.

For example, as shown in figure 5, when the frequency reaches 50kHz, the muscle contraction is substantially negligible, and the higher the frequency, the less pronounced the muscle contraction. However, when the frequency is further increased, the cell membrane insulation effect is reduced, the voltage across the membrane is reduced, and the corresponding electric field force is also reduced, so that a suitable frequency range needs to be selected. For example, in some examples, the pulse frequency of the second pulse may be in the range of 40kHz to 50kHz, based on which both the reduction or elimination of muscle contraction and the securing of sufficient electric force are possible. For example, in some examples, the pulse frequency of the second pulse may be 50kHz for better processing.

For example, the first pulse may have an amplitude of-10 kV to +10kV, and the second pulse may have an amplitude of-10 kV to +10 kV. For example, in some embodiments, if a sine wave pulse is used, the maximum amplitude of the second pulse may be in a high voltage range of 500V to 5000V, and based on this amplitude, for example, an efficient reaming effect on the cell opening may be achieved in the reaming stage.

For example, the first pulse module may be further configured to: a first initial pulse comprising a square wave is generated and transformed into a first pulse. The second pulse module may be further configured to: a second initial pulse comprising a square wave is generated and transformed into a second pulse. The second initial pulse comprises a square wave having waveform parameters different from those of the first initial pulse.

Fig. 6 is a schematic diagram illustrating another pulse processing apparatus provided in at least one embodiment of the present disclosure.

As shown in fig. 6, the first pulse module 110 may include a first pulse generation unit 111, a first pulse modulation unit 112, and a first voltage modulation unit 113. At a first time (e.g., a tapping stage start time), the controller 140 may control the first pulse generating unit 111 to release a first initial pulse, which may be a square wave pulse of a narrow pulse width and may have a lower initial voltage (e.g., 3V). The first pulse modulation unit 112 receives the first initial pulse and performs a preliminary modulation on the first initial pulse, for example, the voltage of the first initial pulse is modulated from the initial voltage to an intermediate voltage (for example, 15V) to adapt to the voltage requirement of the subsequent first voltage modulation unit 113 for the square wave. After the first voltage modulation unit 113 receives the preliminarily modulated first initial pulse sent by the first pulse modulation unit 112, the high-voltage direct-current power supply 150 may be used to perform high-voltage modulation on the first initial pulse, for example, the voltage amplitude of the first initial pulse is modulated from 15V to more than 500V, and a low-voltage square wave with relatively low energy is converted into a high-voltage square wave with relatively high energy. And the first voltage modulation unit 113 may control the pulse width of the first initial pulse to be, for example, between 1 μ s and 10 μ s. The pulse output by the first voltage modulation unit is a first pulse, and then the first pulse may be output to the electrode needle unit via the output terminal 130.

For example, the first voltage modulation unit 113 may be implemented as an IGBT (Insulated Gate Bipolar Transistor) element, the first voltage modulation unit 113 may control an on-time of a waveform, and the high voltage dc power supply 150 may control an amplitude of the waveform. For example, the first voltage modulation unit 113 turns on the square wave for 5 μ s, and the high voltage dc power supply may high-voltage modulate the square wave for 5 μ s. For example, the high voltage direct current power supply is 1000V, the amplitude of the square wave of 5 μ s can reach 1000V, and the pulse width and amplitude of the square wave can be adjusted.

For example, as shown in fig. 6, the second pulse module may include a second pulse generation unit 121, a second pulse modulation unit 122, an operational amplifier 123, an integration circuit 124, and a second voltage modulation unit 125. For example, the second pulse generating unit 121 is configured to release the second initial pulse. The operational amplifier 123 is configured to perform an operational amplification process on the second initial pulse, and convert the square wave in the second initial pulse into a triangular wave. The integrator circuit 124 is configured to transform the triangular wave into a sine wave comprised by the second pulse.

For example, at a second time (e.g., a reaming phase start time), the controller 140 may control the second pulse generating unit 121 to release a second initial pulse, which may be a square wave pulse, which may have a lower initial voltage. The second pulse modulation unit 122 receives the second initial pulse and performs preliminary modulation on the second initial pulse, for example, modulates the voltage of the second initial pulse from the initial voltage to an intermediate voltage to adapt to subsequent operation requirements. The second pulse modulation unit 122 transmits the preliminarily modulated second initial pulse to the operational amplifier 123, converts the square wave into a triangular wave by using the operational amplifier 123, and then converts the triangular wave into a sine wave by using the integrator circuit (RC non-element integrator circuit) 124. The second voltage modulation unit 125 may perform high-voltage modulation on the converted sine wave by using the high-voltage dc power supply 150, for example, the voltage amplitude of the sine wave is modulated to be more than 500V, and a low-voltage sine wave with relatively low energy is converted into a high-voltage sine wave with relatively high energy. The second voltage modulation unit 125 may also be implemented as an IGBT element, and the principle of adjusting the voltage amplitude and the pulse width by combining the second voltage modulation unit 125 with the high voltage dc power supply 150 may be referred to the above description about the first voltage modulation unit 113, and will not be described herein again. The pulse output from the second voltage modulation unit 125 is a second pulse, and then the second pulse may be output to the electrode needle unit via the output terminal 130. For example, the frequency of the second initial pulse may be the same as the frequency of the second pulse, i.e., the frequency of the pulse may not be changed after passing through the second pulse modulation unit 122, the operational amplifier 123, the integration circuit 124, and the second voltage modulation unit.

For example, in some examples, the first initial pulse (square wave pulse) and the second initial pulse (square wave pulse) may be the same wavelength, e.g., both wavelengths are 5 μ β. However, in the field of irreversible electroporation, since the opening and reaming of cell membranes require different wavelengths, the first pulse may have a high voltage narrow pulse waveform, and the second pulse may have a frequency in the range of 25kHz to 200kHz, preferably in the range of 40kHz to 50kHz, wherein the frequency of 50kHz is preferred, i.e. the sine wave effect of square wave conversion with a pulse width of 20 mus is preferred.

For example, the first pulse module and the second pulse module may increase or decrease the included cells as appropriate. For example, in some examples, the first pulse module 110 may not include the first pulse modulation unit 112, for example, the first pulse generation unit may directly emit the square wave required by the first voltage modulation unit 113 without performing preliminary modulation by the first pulse modulation unit 112. Similarly, the second pulse module 120 may not include the second pulse modulation unit 122.

Fig. 7 is a schematic diagram of another pulse processing apparatus provided in at least one embodiment of the present disclosure.

As shown in fig. 7, for example, some of the cells in the first pulse module and the second pulse module shown in fig. 6 may be merged or broken down. For example, in some examples, the first pulse generating unit 111 and the second pulse generating unit 121 may be combined into one pulse generating unit 101, and the first initial pulse and the second initial pulse are released by the pulse generating unit 101 in a time-sharing manner, for example, the first initial pulse is released in the hole drilling stage and the second initial pulse is released in the hole expanding stage. The first pulse modulation unit 112 and the second pulse modulation unit 122 may be combined into one pulse modulation unit 102, and the pulse modulation unit 102 may be used to perform preliminary modulation on the first initial pulse and the second initial pulse in a time-sharing manner. The second initial pulse after the preliminary modulation needs to undergo the waveform conversion through the operational amplifier 103 and the integration voltage 104. In some examples, the first voltage modulation unit 113 and the second voltage modulation unit 125 may also be combined into one voltage modulation unit 105, and the voltage modulation unit 105 and the high voltage dc power supply 106 are used to perform high voltage modulation and pulse width adjustment on the first initial pulse subjected to preamble processing (for example, the first initial pulse subjected to the pulse modulation unit 102) and the second initial pulse subjected to preamble processing (for example, the second initial pulse subjected to the pulse modulation unit 102, the operational amplifier 103, and the integration circuit 104) in a time-sharing manner. In this case, the first pulse module may be composed of the pulse generation unit 101, the pulse modulation unit 102, and the voltage modulation unit 105, and the second pulse module may be composed of the pulse generation unit 101, the pulse modulation unit 102, the operational amplifier, the integration circuit 104, and the voltage modulation unit 105.

For example, the second pulse module is further configured to: a third initial pulse comprising a sine wave is generated and modulated into the second pulse. For example, the second pulse module may directly generate a sine wave without waveform conversion. In this case, the second pulse generating unit 121 may directly release the sine wave, and the sine wave may be directly transmitted to the second pulse modulating unit 125 after being primarily modulated by the second pulse modulating unit 122. For example, the second pulse module 120 may include only the second pulse generation unit 121, the second pulse modulation unit 122, and the second voltage modulation unit 125, without including the operational amplifier 123 and the integration circuit 124. I.e. at a second moment (e.g. a reaming phase start moment), the controller 140 may control the second pulse generating unit 121 to release a third initial pulse, which may be a sine wave pulse, which may have a lower initial voltage. The second pulse modulation unit 122 receives the third initial pulse and performs preliminary modulation on the third initial pulse, for example, modulates the voltage of the third initial pulse from the initial voltage to an intermediate voltage to adapt to subsequent operation requirements. The second pulse modulation unit 122 transmits the preliminarily modulated third initial pulse to the second voltage modulation unit 125, and then the second voltage modulation unit 125 may perform high-voltage modulation on the preliminarily modulated third initial pulse by using the high-voltage direct-current power supply 150, for example, the voltage amplitude of the sine wave is modulated to be more than 500V, and a low-voltage sine wave with relatively low energy is converted into a high-voltage sine wave with relatively high energy. Based on this, the efficiency of the processing can be improved.

For example, the components of the first pulse module 110, the second pulse module 120, the output 130, and the controller 140 included in the pulse processing apparatus may be hardware, software, firmware, or any feasible combination thereof. For example, the components of the first pulse module 110, the second pulse module 120, the output 130, and the controller 140 may be dedicated or general circuits, chips, or devices, and may also be a combination of a processor and a memory. The embodiments of the present disclosure are not limited in this regard to the specific implementation forms of the above units. The components and configuration of the pulse processing apparatus 100 shown in fig. 1, 6, and 7 are exemplary only, and not limiting, and the pulse processing apparatus may include other components and configurations as desired.

Another aspect of the embodiments of the present disclosure also provides a pulse processing method.

Fig. 8 shows a flowchart of a pulse processing method according to at least one embodiment of the present disclosure.

As shown in fig. 8, the pulse processing method includes steps S310 and S320.

Step S310: providing and outputting a first pulse to be applied to the target tissue cells during the aperturing stage, the first pulse for irreversible electroporation ablation of the target tissue cells, the first pulse having a first waveform for forming an aperture in the target tissue cells;

step S320: and providing and outputting a second pulse to be applied to the target tissue cells during the reaming stage, the second pulse being for irreversible electroporation ablation of the target tissue cells, the second pulse having a second waveform for enlarging the aperture of the opening, the second waveform having less low frequency content than the first waveform or the second waveform containing no low frequency content, the low frequency content being a content having a frequency in the frequency domain below a predetermined frequency threshold.

For example, the pulse processing method provided in an embodiment of the present disclosure further includes: and controlling the first pulse and the second pulse to be output according to a preset sequence.

For example, in a pulse processing method provided in an embodiment of the present disclosure, step S310 may include: and sending a first control instruction to the first pulse module to enable the first pulse module to output a first pulse to the output end in the hole opening stage. Step S320 may include: and sending a second control instruction to the second pulse module to enable the second pulse module to output a second pulse to the output end in the reaming stage.

For example, in a pulse processing method provided in an embodiment of the present disclosure, step S310 may include: a first initial pulse comprising a square wave is generated and transformed into a first pulse. Step S320 may include: generating a second initial pulse comprising a square wave and transforming the second initial pulse into a second pulse, the second initial pulse comprising a square wave having waveform parameters different from those of the first initial pulse.

For example, in a pulse processing method provided by an embodiment of the present disclosure, transforming a second initial pulse into a second pulse includes: performing operational amplification processing on the second initial pulse, and converting the square wave in the second initial pulse into a triangular wave; the triangular wave is transformed into a sine wave comprised by the second pulse.

For example, in a pulse processing method provided in an embodiment of the present disclosure, step S320 may include: a third initial pulse comprising a sine wave is generated and modulated into the second pulse.

For example, in a pulse processing method provided by an embodiment of the present disclosure, the second pulse includes a plurality of groups of sine waves, each group of sine waves includes at least one cycle of sine waves, each group of sine waves is spaced apart by a predetermined time period, and no pulse is provided for the predetermined time period.

For example, an embodiment of the present disclosure provides a pulse processing method further including: and acquiring a first time period corresponding to the hole opening stage and a second time period corresponding to the hole expanding stage. Step S310 may include: the method comprises the following steps: and in the first time period, controlling the first pulse module to output the first pulse to the output end. Step S320 may include: and controlling the second pulse module to output the second pulse to the output end in the second time period.

It should be noted that, in the embodiment of the present disclosure, each step of the pulse processing method corresponds to each module and unit of the pulse processing apparatus, and for a specific function of the pulse processing method, reference may be made to the description related to the pulse processing apparatus, and details are not described here again.

At least one embodiment of the present disclosure also provides an electronic device comprising a processor and a memory, the memory including one or more computer program modules. One or more computer program modules are stored in the memory and configured to be executed by the processor, the one or more computer program modules comprising instructions for implementing the pulse processing method described above. The electronic device can eliminate or weaken the stimulation of low-frequency components to muscles, further avoid strong muscle contraction and reduce the effect of water electrolysis.

Fig. 9 is a schematic block diagram of an electronic device provided in some embodiments of the present disclosure. As shown in fig. 9, the electronic device 400 includes a processor 410 and a memory 420. Memory 420 is used to store non-transitory computer readable instructions (e.g., one or more computer program modules). The processor 410 is configured to execute non-transitory computer readable instructions that, when executed by the processor 410, may perform one or more of the steps of the pulse processing methods described above. The memory 420 and the processor 410 may be interconnected by a bus system and/or other form of connection mechanism (not shown).

For example, the processor 410 may be a Central Processing Unit (CPU), a Graphics Processing Unit (GPU), or other form of processing unit having data processing capabilities and/or program execution capabilities. For example, the Central Processing Unit (CPU) may be an X86 or ARM architecture or the like. The processor 410 may be a general-purpose processor or a special-purpose processor that may control other components in the electronic device 400 to perform desired functions.

For example, memory 420 may include any combination of one or more computer program products that may include various forms of computer-readable storage media, such as volatile memory and/or non-volatile memory. Volatile memory can include, for example, random Access Memory (RAM), cache memory (or the like). The non-volatile memory may include, for example, read Only Memory (ROM), hard disk, erasable Programmable Read Only Memory (EPROM), portable compact disk read only memory (CD-ROM), USB memory, flash memory, and the like. One or more computer program modules may be stored on the computer-readable storage medium and executed by processor 410 to implement various functions of electronic device 400. Various applications and various data, as well as various data used and/or generated by the applications, and the like, may also be stored in the computer-readable storage medium.

It should be noted that, in the embodiment of the present disclosure, reference may be made to the above description about the pulse processing method for specific functions and technical effects of the electronic device 400, and details are not described herein again.

Fig. 10 is a schematic block diagram of another electronic device provided by some embodiments of the present disclosure. The electronic device 500 is, for example, suitable for implementing the pulse processing method provided by the embodiments of the present disclosure. The electronic device 500 may be a terminal device or the like. It should be noted that the electronic device 500 shown in fig. 10 is only an example, and does not bring any limitation to the functions and the scope of the application of the embodiments of the present disclosure.

As shown in fig. 10, electronic device 500 may include a processing means (e.g., central processing unit, graphics processor, etc.) 510 that may perform various appropriate actions and processes in accordance with a program stored in a Read Only Memory (ROM) 520 or a program loaded from a storage means 580 into a Random Access Memory (RAM) 530. In the RAM530, various programs and data necessary for the operation of the electronic apparatus 500 are also stored. The processing device 510, ROM 520 and RAM530 are connected to each other by a bus 540. An input/output (I/O) interface 550 is also connected to bus 540.

Generally, the following devices may be connected to I/O interface 550: input devices 560 including, for example, a touch screen, touch pad, keyboard, mouse, camera, microphone, accelerometer, gyroscope, etc.; output devices 570 including, for example, a Liquid Crystal Display (LCD), speakers, vibrators, or the like; storage 580 including, for example, magnetic tape, hard disk, etc.; and a communication device 590. The communication device 590 may allow the electronic apparatus 500 to perform wireless or wired communication with other electronic apparatuses to exchange data. While fig. 10 illustrates an electronic device 500 having various means, it is to be understood that not all illustrated means are required to be implemented or provided, and that the electronic device 500 may alternatively be implemented or provided with more or less means.

For example, according to an embodiment of the present disclosure, the above-described pulse processing method may be implemented as a computer software program. For example, embodiments of the present disclosure include a computer program product comprising a computer program carried on a non-transitory computer readable medium, the computer program comprising program code for performing the pulse processing method described above. In such an embodiment, the computer program may be downloaded and installed from a network through the communication device 590, or installed from the storage device 580, or installed from the ROM 520. When executed by the processing device 510, the computer program may implement the functions defined in the pulse processing method provided by the embodiments of the present disclosure.

At least one embodiment of the present disclosure also provides a computer-readable storage medium for storing non-transitory computer-readable instructions that, when executed by a computer, may implement the pulse processing method described above. With the computer-readable storage medium, stimulation of the muscle by the low frequency component can be eliminated or reduced, so that strong muscle contraction can be avoided, and the effect of electrolyzed water can be reduced.

Fig. 11 is a schematic diagram of a storage medium according to some embodiments of the present disclosure. As shown in fig. 11, computer-readable storage medium 600 is used to store non-transitory computer-readable instructions 610. For example, the non-transitory computer readable instructions 610, when executed by a computer, may perform one or more steps according to the pulse processing method described above.

For example, the storage medium 600 may be applied to the electronic device 400 described above. The storage medium 600 may be, for example, the memory 420 in the electronic device 400 shown in fig. 9. For example, the related description about the storage medium 600 may refer to the corresponding description of the memory 420 in the electronic device 400 shown in fig. 9, and is not repeated here.

The following points need to be explained:

(1) The drawings of the embodiments of the disclosure only relate to the structures related to the embodiments of the disclosure, and other structures can refer to common designs.

(2) Without conflict, embodiments of the present disclosure and features of the embodiments may be combined with each other to arrive at new embodiments.

The above description is only a specific embodiment of the present disclosure, but the scope of the present disclosure is not limited thereto, and the scope of the present disclosure should be subject to the scope of the claims.

Claims

1. A pulse processing apparatus comprising:

a first pulse module configured to provide a first pulse;

a second pulse module configured to provide a second pulse;

an output configured to receive and output the first pulse and to receive and output the second pulse;

a controller configured to control the first pulse module to output the first pulse to the output end during a trepanning phase and to control the second pulse module to output the second pulse to the output end during a reaming phase,

wherein the first pulse and the second pulse are used for irreversible electroporation ablation of target tissue cells, the first pulse has a first waveform for forming an opening in the target tissue cells, the first waveform is used for forming an opening in cell membranes of the target tissue cells, the second pulse has a second waveform for enlarging the aperture of the opening, the opening forms irreversible perforations in the cell membranes of the target tissue cells under the condition of expanding to a certain extent, so as to achieve ablation of the target tissue cells, the low-frequency component of the second waveform is less than that of the first waveform or the second waveform does not contain a low-frequency component, the low-frequency component is a component with a frequency lower than a preset frequency threshold value in a frequency domain, the output end outputs the first pulse first, and outputs the second pulse after forming a required opening in the target tissue cells until irreversible expansion of the opening is achieved.

2. The pulse processing apparatus of claim 1, wherein the first waveform comprises a square wave or a square wave and the second waveform comprises a sine wave.

3. A pulse processing apparatus according to claim 1 or 2, wherein the pulse frequency of the second pulses lies in the range of 25kHz-200 kHz.

4. A pulse processing apparatus according to claim 3, wherein a pulse frequency of the second pulses is in a range of 40kHz-50 kHz.

5. The pulse processing apparatus of claim 1 or 2, wherein the controller is configured to: and controlling the first pulse and the second pulse to be output according to a preset sequence.

6. A pulse processing apparatus according to claim 1 or 2, wherein the first pulse has an amplitude between-10 kV and +10kV and the second pulse has an amplitude between-10 kV and +10 kV.

7. The pulse processing apparatus of claim 1 or 2, wherein the controller is further configured to:

and sending a first control instruction to the first pulse module to enable the first pulse module to output the first pulse to the output end in the hole opening stage, and sending a second control instruction to the second pulse module to enable the second pulse module to output the second pulse to the output end in the hole expanding stage.

8. The pulse processing apparatus according to claim 1 or 2,

the first pulse module is further configured to: generating a first initial pulse comprising a square wave and transforming the first initial pulse into the first pulse;

the second pulse module is further configured to: generating a second initial pulse comprising a square wave and transforming the second initial pulse into the second pulse,

wherein the second initial pulse comprises a square wave having waveform parameters different from those of the first initial pulse.

9. The pulse processing apparatus of claim 8, wherein the second pulse module comprises:

the operational amplifier is configured to perform operational amplification processing on the second initial pulse and convert a square wave in the second initial pulse into a triangular wave;

an integration circuit configured to transform the triangular wave into a sine wave contained by the second pulse.

10. The pulse processing apparatus according to claim 1 or 2,

the second pulse module is further configured to: a third initial pulse comprising a sine wave is generated and modulated into the second pulse.

11. A pulse processing apparatus according to claim 2, wherein the second pulse comprises a plurality of groups of sinusoids, each group comprising at least one cycle of sinusoids, each group being spaced apart by a predetermined length of time within which no pulse is provided.

12. The pulse processing apparatus of claim 1 or 2, wherein the controller is further configured to:

acquiring a first time period corresponding to the hole opening stage and a second time period corresponding to the hole expanding stage;

controlling the first pulse module to output the first pulse to the output end in the first time period;

and controlling the second pulse module to output the second pulse to the output end in the second time period.

13. An electronic device, comprising:

a processor;

a memory including one or more computer program modules;

wherein the one or more computer program modules are stored in the memory and configured to be executed by the processor, the one or more computer program modules comprising instructions for implementing a method of:

providing and outputting a first pulse to be applied to the target tissue cells during the aperturing phase;

providing and outputting a second pulse to be applied to the target tissue cells during a reaming phase;

wherein the first pulse and the second pulse are used for irreversible electroporation ablation of the target tissue cell, the first pulse has a first waveform for forming an opening in the target tissue cell, the first waveform is used for forming an opening in a cell membrane of the target tissue cell, the second pulse has a second waveform for enlarging the aperture of the opening, the opening forms an irreversible perforation in the cell membrane of the target tissue cell when expanded to a certain extent, thereby achieving ablation of the target tissue cell, the low-frequency component of the second waveform is less than that of the first waveform or the second waveform does not contain a low-frequency component, and the low-frequency component is a component with a frequency lower than a preset frequency threshold in a frequency domain;

wherein, the output control sequence of the first pulse and the second pulse is as follows: and controlling to output the first pulse, and after the required open pore is formed on the target tissue cell, controlling to output the second pulse until the open pore realizes irreversible expansion.

14. A computer readable storage medium storing non-transitory computer readable instructions which, when executed by a computer, can implement a method comprising:

providing and outputting a second pulse to be applied to the target tissue cells during the reaming stage;