CN115645030A - Pulse generating device, irreversible electroporation apparatus, and related methods - Google Patents

Abstract

The application provides a pulse generator, irreversible electroporation equipment and relevant method, in pulse generator, the first pulse generator that corresponds and second pulse generator adopt same high voltage charging power supply to provide high voltage, make two kinds of high voltage pulse signal of positive and negative that produce not have the delay like this, anodal high voltage pulse signal and/or negative pole high voltage pulse signal that obtain do not have trailing effect, the effect of melting of the tissue of waiting to melt has further been guaranteed, and, only with a high voltage charging power supply, can reduce pulse generator's volume.

Description

Pulse generating device, irreversible electroporation apparatus, and related methods

Technical Field

The present application relates to the field of pulse ablation techniques, and more particularly, to a pulse generating device, irreversible electroporation apparatus, and related methods.

Background

Irreversible electroporation is to apply an external high-voltage pulse electric field to cells to make the cell membrane irreversibly damaged, i.e. irreversible electroporation, so that the physiological balance inside and outside the cells is broken, and finally the cells are killed. Therefore, the method can be applied to the treatment of tumor focus, and can lead tumor cells to die through irreversible electroporation, thereby achieving the aim of clinical treatment.

However, in the prior art, the charging power supply of the positive polarity pulse generating unit and the charging power supply of the negative polarity pulse generating unit of the pulse generating device are independent of each other, which easily causes delay of the charging and discharging signals and a pulse waveform tailing effect.

Disclosure of Invention

It is therefore an objective of the claimed invention to provide a pulse generating device, an irreversible electroporation apparatus and related methods to solve or partially solve the above-mentioned problems.

With the foregoing in mind, a first aspect of the present application provides a pulse generating device comprising: the ablation device comprises a first pulse generating circuit and a second pulse generating circuit which share a high-voltage charging power supply, wherein the output end of the first pulse generating circuit is provided with a first electrode, the output end of the second pulse generating circuit is provided with a second electrode, and the first electrode and the second electrode are used for being arranged on tissue to be ablated;

the first pulse generating circuit is configured to store the positive high voltage sent by the high-voltage charging power supply according to the positive high-voltage pulse control signal, expand the stored positive high voltage to a preset multiple to generate a positive high-voltage pulse signal, apply the positive high-voltage pulse signal to the tissue to be ablated through the first electrode, and simultaneously control the second electrode of the second pulse generating circuit to be communicated with the ground end;

and/or the presence of a gas in the atmosphere,

the second pulse generating circuit is configured to store the negative high voltage sent by the high-voltage charging power supply according to the negative high-voltage pulse control signal, and expand the stored negative high voltage to a preset multiple to generate a negative high-voltage pulse signal which is applied to the tissue to be ablated through the second electrode, and meanwhile, the first electrode of the first pulse generating circuit is controlled to be communicated with the ground terminal.

Based on the same inventive concept, a second aspect of the present application provides an irreversible electroporation apparatus comprising:

a control unit, the pulse generating device of the first aspect;

the control unit is configured to control the operation of the pulse generating device and the data acquisition and processing unit;

the pulse generating device is configured to control the first pulse generating circuit and the second pulse generating circuit to generate a positive electrode high-voltage pulse signal and/or a negative electrode high-voltage pulse signal to be applied to the tissue to be ablated according to the control signal of the control unit.

Based on the same inventive concept, a third aspect of the present application provides a pulse generating method applied to the pulse generating apparatus of the first aspect, the pulse generating method including:

placing a first electrode of a first pulse generating circuit and a second electrode of a second pulse generating circuit on a tissue to be ablated, and then receiving a control signal;

in response to the fact that the control signal is determined to be a positive high-voltage pulse control signal, the first pulse generating circuit is used for storing and processing positive high voltage transmitted by the high-voltage charging power supply, the stored positive high voltage is expanded to a preset multiple to generate a positive high-voltage pulse signal, the positive high-voltage pulse signal is applied to the tissue to be ablated through the first electrode, and meanwhile a second electrode of the second pulse generating circuit is controlled to be communicated with a ground end;

and in response to the control signal is determined to be a negative high-voltage pulse control signal, the second pulse generating circuit is utilized to store and process the negative high voltage transmitted by the high-voltage charging power supply, the stored negative high voltage is expanded to a preset multiple to generate a negative high-voltage pulse signal, the negative high-voltage pulse signal is applied to the tissue to be ablated through the second electrode, and meanwhile, the first electrode of the first pulse generating circuit is controlled to be communicated with the ground terminal.

Based on the same inventive concept, a fourth aspect of the present application provides an irreversible electroporation method applied to the irreversible electroporation apparatus according to the second aspect, the irreversible electroporation method comprising:

generating a control signal by using a control unit, and sending the control signal to the pulse generating device;

and controlling the first pulse generating circuit and the second pulse generating circuit to generate a positive electrode high-voltage pulse signal and/or a negative electrode high-voltage pulse signal to be applied to the tissue to be ablated by the pulse generating device according to the control signal.

From the above, in the pulse generating device, the corresponding first pulse generating circuit and the second pulse generating circuit adopt the same high-voltage charging power supply to provide high voltage, so that the generated positive and negative high-voltage pulse signals are not delayed, the obtained positive high-voltage pulse signal and/or negative high-voltage pulse signal have no trailing effect, the ablation effect of the tissue to be ablated is further ensured, and the size of the pulse generating device can be reduced by only using one high-voltage charging power supply.

Drawings

In order to more clearly illustrate the technical solutions in the present application or related technologies, the drawings required for the embodiments or related technologies in the following description are briefly introduced, and it is obvious that the drawings in the following description are only the embodiments of the present application, and it is obvious for those skilled in the art that other drawings can be obtained according to these drawings without creative efforts.

FIG. 1-1 is a schematic diagram of a circuit configuration of a pulse generating device according to an embodiment of the present application;

FIGS. 1-2 are schematic diagrams of another circuit configuration of a pulse generating device according to an embodiment of the present application;

FIGS. 1-3 are schematic diagrams of hierarchical circuit structures of pulse generating devices according to embodiments of the present application;

FIGS. 1-4 are schematic circuit diagrams of a pulse generator with 3 sets of hierarchical circuits according to an embodiment of the present application;

FIG. 2 is a schematic structural view of an irreversible electroporation apparatus according to an embodiment of the present application;

FIG. 3-1 is a schematic circuit diagram illustrating a charging process according to an embodiment of the present disclosure;

FIG. 3-2 is a schematic diagram of a circuit structure for generating a positive high voltage pulse signal according to an embodiment of the present application;

3-3 are schematic circuit diagrams of the negative extreme high voltage pulse signal generated according to the present embodiment;

FIGS. 3-4 are schematic diagrams of the circuit structure for generating a positive low current according to an embodiment of the present application;

FIGS. 3-5 are schematic diagrams of negative very low current generating circuits according to embodiments of the present disclosure;

FIGS. 3-6 are timing diagrams of pulse signals;

FIG. 4 is a flow chart of a pulse generation method according to an embodiment of the present application;

fig. 5 is a flowchart of an irreversible electroporation method according to an embodiment of the present disclosure.

Detailed Description

In order to make the objects, technical solutions and advantages of the present application more apparent, the present application is further described in detail below with reference to specific embodiments and the accompanying drawings.

It should be noted that technical terms or scientific terms used in the embodiments of the present application should have a general meaning as understood by those having ordinary skill in the art to which the present application belongs, unless otherwise defined. The use of "first," "second," and similar terms in the embodiments of the present application is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another. 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 merely 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.

Based on the description of the background art, the high-voltage pulse source is a core link of the irreversible electroporation tumor ablation technology, and at present, most of the high-voltage pulse sources are based on a Marx high-voltage forming circuit of a solid-state switch. With the continuous promotion of the clinical application of irreversible electroporation tumor ablation, clinicians find that the ablation effect is difficult to meet the current treatment requirement only by checking the ablation effect in a nuclear magnetic resonance imaging or CT scanning mode for 24h or more after operation, and it is particularly necessary to evaluate the curative effect in real time in the irreversible electroporation tumor ablation process so as to determine the optimal treatment stopping time point. The real-time change of the impedance spectrum of the tissue to be ablated in the irreversible electroporation process is used for reflecting the ablation effect, and the ablation effect is expected to become a breakthrough for evaluating the curative effect in real time.

Based on the above description, an embodiment of the present disclosure provides a pulse generating apparatus 100, as shown in fig. 1-1, including:

a first pulse generating circuit 11 and a second pulse generating circuit 12 which share a high-voltage charging power source HVDC, wherein an output end of the first pulse generating circuit 11 is provided with a first electrode 111, an output end of the second pulse generating circuit 12 is provided with a second electrode 121, and the first electrode 111 and the second electrode 121 are used for being arranged on a tissue to be ablated;

the first pulse generating circuit 11 is configured to store the positive high voltage transmitted by the high-voltage charging power source HVDC according to the positive high-voltage pulse control signal, and expand the stored positive high voltage to a predetermined multiple to generate a positive high-voltage pulse signal, which is applied to the tissue to be ablated through the first electrode 111, and meanwhile, the second electrode 121 of the second pulse generating circuit 12 is controlled to be connected to the ground;

and/or the presence of a gas in the atmosphere,

the second pulse generating circuit 12 is configured to store the negative high voltage transmitted by the high-voltage charging power source HVDC according to the negative high-voltage pulse control signal, and expand the stored negative high voltage to a predetermined multiple to generate a negative high-voltage pulse signal, which is applied to the tissue to be ablated through the second electrode 121, and at the same time, control the first electrode 111 of the first pulse generating circuit 11 to be communicated with the ground;

wherein the predetermined multiple is more than or equal to 1. The predetermined multiple can be adjusted correspondingly according to actual needs.

In specific implementation, the direction of the current is defined to be positive in the direction from the upper side to the lower side of the tissue to be ablated, and vice versa. The tissue to be ablated in the present application is tumor tissue with lesion, and the first electrode 111 and the second electrode 121 are placed on the tissue to be ablated. If the control signal is a continuous positive electrode high-voltage pulse control signal, generating a continuous positive electrode high-voltage pulse train according to the generation mode of the positive electrode high-voltage pulse signal; if the control signal is a continuous negative high-voltage pulse control signal, a continuous negative high-voltage pulse train is generated according to the generation mode of the negative high-voltage pulse signal; if the control signal is a continuously alternating positive electrode high-voltage pulse control signal and negative electrode high-voltage pulse control signal, the alternating control is performed according to the generation mode of the positive electrode high-voltage pulse signal and the negative electrode high-voltage pulse signal, and then the bipolar high-voltage pulse train is generated.

Through the scheme, in the pulse generating device 100, the first pulse generating circuit 11 and the second pulse generating circuit 12 adopt the same high-voltage charging power source HVDC to provide high voltage, so that the generated positive and negative high-voltage pulse signals are not delayed, the obtained positive high-voltage pulse signal and/or negative high-voltage pulse signal have no trailing effect, and the ablation effect of the tissue to be ablated is further ensured.

In some embodiments, the pulse generating device 100 further comprises:

a first low-voltage direct-current power supply DC1 connected to the output end of the first pulse generating circuit 11, configured to disconnect the first pulse generating circuit 11 from the high-voltage charging power supply HVDC according to a positive low-voltage control signal, and control the first low-voltage direct-current power supply DC1 to apply a positive low-voltage current to the tissue to be ablated through the first electrode 111, and simultaneously control the second electrode 121 of the second pulse generating circuit 12 to be grounded;

and/or the presence of a gas in the gas,

and a second low-voltage direct-current power supply DC2 connected to the output end of the second pulse generating circuit 12, and configured to disconnect the second pulse generating circuit 12 from the high-voltage charging power supply HVDC according to a negative low-voltage control signal, control the second low-voltage direct-current power supply DC2 to apply a negative low-voltage current to the tissue to be ablated through the second electrode 121, and simultaneously control the first electrode 111 of the first pulse generating circuit 11 to be connected to the ground.

In specific implementation, if the control signal is a continuous positive low-voltage control signal, a first low-voltage direct current power supply DC1 is used to continuously apply a positive low-voltage current to the tissue to be ablated in the manner described above; if the control signal is a continuous negative low-voltage control signal, continuously applying a negative low-voltage current to the tissue to be ablated by using the second low-voltage direct current power supply DC2 according to the manner described above; if the control signal is a continuously alternating positive low-voltage control signal and negative low-voltage control signal, the alternating control is performed according to the above-described generation manner of the positive low-voltage current and the negative low-voltage current, so as to generate a bipolar low-voltage current to be applied to the tissue to be ablated.

The positive electrode high voltage pulse train, the negative electrode high voltage pulse train, the bipolar high voltage pulse train, the positive electrode low voltage current, the negative electrode low voltage current and the bipolar low voltage current may be combined and applied to the tissue to be ablated for ablation treatment, and the specific combination mode and application time may be adjusted according to the specific pathological change condition of the tissue to be ablated, which is not limited specifically herein.

In some embodiments, the positive low voltage current and/or the negative low voltage current is applied to the tissue to be ablated in the interval of the positive high voltage pulse signal and/or the negative high voltage pulse signal.

By the scheme, the corresponding low-voltage current can be applied to the tissue to be ablated when the tissue to be ablated is subjected to high-voltage irreversible electroporation ablation, and the tumor cells can be electrolyzed and die due to the fact that the continuous low-voltage direct current is applied after the high-voltage pulse signals are subjected to irreversible electroporation ablation on the tumor cells (namely, the tissue to be ablated), so that the ablation range is expanded.

In some embodiments, the first low voltage DC power DC1 is connected to the output terminal of the first pulse generating circuit 11 through a first low voltage DC power switch SD3-1, and the first low voltage DC power switch SD3-1 is configured to be turned on after receiving the positive low voltage control signal;

the second low voltage DC power supply DC2 is connected to the output end of the second pulse generating circuit 12 through a second low voltage DC power supply switch SD3-2, and the second low voltage DC power supply switch SD3-2 is configured to be turned on after receiving the negative low voltage control signal.

When the device is specifically implemented, the two low-voltage direct-current power switches can be used for better controlling the on-off of the two low-voltage direct-current power supplies according to the control signal. If the control signal is a positive low-voltage control signal, the first low-voltage direct-current power switch SD3-1 is switched on, and a positive low-voltage current is applied to the tissue to be ablated by using a first low-voltage direct-current power supply DC1 through the first electrode 111; if the control signal is a negative low-voltage control signal, the second low-voltage direct-current power switch SD3-2 is turned on, and a negative low-voltage current is applied to the tissue to be ablated through the second electrode 121 by using the second low-voltage direct-current power supply DC 2. The two are alternately switched on and off to generate bipolar low-voltage current to be applied to the tissue to be ablated.

In some embodiments, the first pulse generating circuit 11 includes:

at least one first diode DH1-1 connected with the high voltage charging power source HVDC;

one end of the first capacitor CH1-1 is connected with the first diode DH1-1, and the other end is connected with a grounding end;

a first switch SH1-1 and a second switch SH1-5, wherein the first switch SH1-1 and the second switch SH1-5 connected in series are connected with the first capacitor CH1-1 in parallel, and the output end of a first pulse generating circuit 11 is arranged on a lead between the first switch SH1-1 and the second switch SH1-5 and is connected with the first electrode 111;

and (c) a second step of,

the second pulse generating circuit 12 includes:

at least one second diode DH2-1 connected with the high voltage charging power source HVDC;

one end of the second capacitor CH2-1 is connected to the second diode DH2-1, and the other end is connected to a ground terminal;

and the third switch SH2-1 and the fourth switch SH2-5 are connected in series, the third switch SH2-1 and the fourth switch SH2-5 are connected in parallel with the second capacitor CH2-1, and the output end of the second pulse generating circuit 12 is arranged on a lead between the third switch SH2-1 and the fourth switch SH2-5 and is connected with the second electrode 121.

In specific implementation, based on the specific circuit, the charging process comprises the following steps: the first switch SH1-1 and the third switch SH2-1 are controlled to be switched off, the second switch SH1-5 and the fourth switch SH2-5 are controlled to be switched on, and the first capacitor CH1-1 and the second capacitor CH2-1 are charged through the high-voltage charging power supply HVDC.

The generation process of the positive high-voltage pulse signal comprises the following steps: the control signal is determined to be a positive electrode high-voltage pulse control signal, the first switch SH1-1 and the fourth switch SH2-5 are controlled to be switched on, the second switch SH1-5 and the third switch SH2-1 are switched off, the first capacitor CH1-1 generates a positive electrode high-voltage pulse signal by the stored positive electrode high voltage, the positive electrode high-voltage pulse signal is applied to the tissue to be ablated through the first electrode 111, and then the positive electrode high-voltage pulse signal flows back to the ground end through the second electrode 121.

The generation process of the negative high-voltage pulse signal comprises the following steps: and determining that the control signal is a negative high-voltage pulse control signal, controlling the first switch SH1-1 and the fourth switch SH2-5 to be switched off, switching the second switch SH1-5 and the third switch SH2-1 on, and applying a stored negative high-voltage generated negative high-voltage pulse signal to the tissue to be ablated through the second electrode 121 by using the second capacitor CH2-1, and then flowing back to the ground end through the first electrode 111.

And (3) generating a positive low-voltage current: the control signal is determined to be a positive low-voltage control signal, the first switch SH1-1, the second switch SH1-5 and the third switch SH2-1 are controlled to be switched off, the fourth switch SH2-5 and the first low-voltage direct-current power switch SD3-1 are controlled to be switched on, positive low-voltage current is applied to the tissue to be ablated through the first electrode 111 by the first low-voltage direct-current power supply DC1, and then the positive low-voltage current flows back to the grounding end through the second electrode 121.

And a negative low-voltage current generation process: and determining the control signal as a negative low-voltage control signal, controlling the first switch SH1-1, the third switch SH2-1 and the fourth switch SH2-5 to be switched off, controlling the second switch SH1-5 and the second low-voltage direct-current power switch SD3-2 to be switched on, applying negative low-voltage current to the tissue to be ablated through the second electrode 121 by using the second low-voltage direct-current power DC2, and then flowing back to the grounding end through the first electrode 111.

In some embodiments, the first diodes DH1-1 are arranged in series at least two; at least two second diodes DH2-1 are arranged in series.

Through the scheme, at least two diodes are connected in series in the two pulse generating circuits, and the function of unidirectional conduction of the diodes is utilized, so that current reverse propagation can be better blocked, and the whole circuit can be better protected.

In some embodiments, at least one grading circuit 13 is further disposed in parallel in the first pulse generating circuit 11 or the second pulse generating circuit 12, and the grading circuit 13 is connected with the first electrode 111 or the second electrode 121;

the classification circuit 13 is configured to expand a voltage value of the positive high-voltage pulse signal or expand a voltage value of the negative high-voltage pulse signal.

The classification circuit 13 includes: one end of the grading diode DH1-3 is connected with the first diode DH1-1 or the second diode DH 2-1;

one end of the grading capacitor CH1-2 is connected with the other end of the grading diode DH1-3, the other end of the grading capacitor CH1-2 is connected with the middle of the first switch SH1-1 and the second switch SH1-5, or the other end of the grading capacitor CH1-2 is connected with the middle of the third switch SH2-1 and the fourth switch SH 2-5;

the first grading switch SH1-2 and the second grading switch SH1-6 are connected in parallel, and the first grading switch SH1-2 and the second grading switch SH1-6 which are connected in series are connected with the grading capacitor CH1-2 in parallel;

wherein, the next grading circuit 13 is connected in parallel at two ends of the first grading switch SH 1-2; or, the first electrode 111/the second electrode 121 are connected to the middle of the first and second grading switches SH1-2 and SH1-6 by a wire.

In specific implementation, since the high voltage of the positive/negative high-voltage pulse signal may not satisfy the requirement of irreversible electroporation on the tissue to be ablated, the voltage value needs to be increased, and the voltage value needs to be increased by using the grading circuit 13. One grading circuit 13 of the present embodiment corresponds to a voltage value that can be raised by a factor of N (e.g., N = 1), and the number of specific grading circuits 13 to be set may be set according to the voltage value required for irreversible electroporation of the tissue to be ablated. For example, if a voltage value needs to be increased by 3 times (i.e., the corresponding predetermined multiple is 3 times), 3 sets of voltage dividing circuits with N =1 are provided in parallel.

Determining that the first switch SH1-1 and the first classification switch SH1-2 of the classification circuit 13 in the first pulse generation circuit 11 are both first main switches; determining that the second switch SH1-5 and the second classification switch SH1-6 of the classification circuit 13 in the first pulse generation circuit 11 are both first charging switches;

determining that the third switch SH2-1 and the first classification switch SH1-2 of the classification circuit 13 in the second pulse generation circuit 12 are both second main switches; it is determined that the fourth switch SH2-5 and the second classification switches SH1-6 of the classification circuit 13 in the second pulse generating circuit 12 are both the second charging switches.

And (3) charging process: the first main switch is controlled to be switched off, the first charging switch is controlled to be switched on, and/or the second main switch is controlled to be switched off, and the second charging switch is controlled to be switched on; all capacitors in the first pulse generating circuit 11 and/or all capacitors in the second pulse generating circuit 12 are charged by means of the same high voltage charging power source HVDC.

A positive high-voltage pulse signal generation process: determining the control signal as an anode high-voltage pulse control signal, controlling a first main switch in the first pulse generating circuit 11 to be switched on and a first charging switch to be switched off, and controlling a second main switch in the second pulse generating circuit 12 to be switched off and a second charging switch to be switched on, discharging all capacitors in the first pulse generating circuit 11 to generate an anode high-voltage pulse signal, applying the anode high-voltage pulse signal to the tissue to be ablated through the first electrode 111, and then flowing back to the ground end through the second electrode 121.

A negative high-voltage pulse signal generation process: determining the control signal as a negative high-voltage pulse control signal, controlling the first main switch in the first pulse generating circuit 11 to be turned off and the first charging switch to be turned on, and controlling the second main switch in the second pulse generating circuit 12 to be turned on and the second charging switch to be turned off, wherein all capacitors in the second pulse generating circuit 12 are discharged to generate a negative high-voltage pulse signal, the negative high-voltage pulse signal is applied to the tissue to be ablated through the second electrode 121, and then flows back to the ground end through the first electrode 111.

And (3) generating a positive low-voltage current: determining the control signal as an anode low-voltage control signal, controlling the first main switch and the first charging switch in the first pulse generating circuit 11 to be switched off, the second main switch in the second pulse generating circuit 12 to be switched off, and the second charging switch to be switched on, applying an anode low-voltage current to the tissue to be ablated through the first electrode 111 by using the first low-voltage direct-current power supply DC1, and then flowing back to the ground end through the second electrode 121.

And a negative low-voltage current generation process: and determining that the control signal is a negative low-voltage control signal, controlling a first main switch in the first pulse generation circuit 11 to be switched off, switching on a first charging switch, switching off a second main switch and a second charging switch in the second pulse generation circuit 12, applying negative low-voltage current to the tissue to be ablated by using a second low-voltage direct-current power supply DC2 through the second electrode 121, and then flowing back to the ground end through the first electrode 111.

Through the scheme of the embodiment, in the pulse generating device 100, the corresponding first pulse generating circuit 11 and the corresponding second pulse generating circuit 12 adopt the same high-voltage charging power source HVDC to provide high voltage, so that the generated positive and negative high-voltage pulse signals are not delayed, the obtained positive high-voltage pulse signal and/or negative high-voltage pulse signal have no trailing effect, the ablation effect of the tissue to be ablated is further ensured, and the size of the pulse generating device 100 can be reduced by only using one high-voltage charging power source HVDC, so that the pulse ablation area is enlarged.

Based on the same inventive concept, the embodiment of the present application provides an irreversible electroporation apparatus 200, including:

a control unit 2, the pulse generating device 1 described in the above embodiments;

the control unit 2 is configured to control the pulse generating device 1 to operate;

the pulse generating device 1 is configured to control the first pulse generating circuit and the second pulse generating circuit to generate a positive high-voltage pulse signal and/or a negative high-voltage pulse signal to be applied to the tissue to be ablated according to the control signal of the control unit 2.

In specific implementation, the control process uses the control unit 2 to generate a control signal and send the control signal to the pulse generating device 1 as follows.

Generating a control signal by a control unit 2, and sending the control signal to the pulse generating device 1;

and controlling the first pulse generating circuit and the second pulse generating circuit to generate a positive electrode high-voltage pulse signal and/or a negative electrode high-voltage pulse signal to be applied to the tissue to be ablated by the pulse generating device 1 according to the control signal.

The corresponding control unit 2 may also generate a positive low voltage control signal and/or a negative low voltage control signal, wherein the positive low voltage control signal and/or the negative low voltage control signal may be generated at intervals of the positive high voltage pulse signal and/or the negative high voltage pulse signal.

Thus, the corresponding positive low-voltage current and/or the negative low-voltage current can be generated according to the positive low-voltage control signal and/or the negative low-voltage control signal according to the description of the corresponding embodiment of the pulse generating device 1, which is not described herein again.

The following is a detailed description of an embodiment of the pulse generating device corresponding to the addition of a 3-group classification circuit:

in the following description of the embodiments, corresponding to circuit portions in the drawings, the black-marked lines and components indicate that they are turned on in the context of the corresponding embodiment, and the gray-marked lines and components indicate that they are not turned on in the context of the corresponding embodiment.

The pulse generating device comprises a pulse generating circuit (namely, a first pulse generating circuit or a second pulse generating circuit) and an electrode needle array module (namely, a first electrode or a second electrode), wherein the pulse generating circuit is used for outputting target pulses to the electrode needle array.

Based on the timing diagrams shown in fig. 3-7, the operation of the two pulse generating circuits is as follows.

Charging:

at the time of 0-T1, the MOS tubes SH1- (5-8) and SH2- (5-8) are in a connected state, the other MOS tubes are in a disconnected state, and the high-voltage charging power supply HVDC charges CH (1-2) - (1-4); the voltages of the 8 CH (1-2) - (1-4) capacitors are all V1. The circuit diagram is shown in fig. 3-1.

At times T1-T2, there is a wait time.

Positive high-voltage pulse signal:

at the time of T2-T3, the MOS tubes SH1- (1-4) and SH2- (5-8) are in an on state, the other MOS tubes are in an off state, and at the time, the CH1- (1-4) provides a positive high-voltage pulse signal of 4V1 to the two ends of a load RL (namely, the tissue to be ablated). The circuit diagram is shown in fig. 3-2.

Positive low-voltage current:

at the time of T3-T4, the MOS transistors SD3-1 and SH2- (5-8) are in the on state, the other MOS transistors are in the off state, and at the time, the DC1 provides the positive low-voltage current of the DC1 to the two ends of the load RL. The circuit diagrams are shown in fig. 3-4.

Negative high-voltage pulse signal:

at the time of T4-T5, the MOS tubes SH1- (5-8) and SH2- (1-4) are in an on state, the other MOS tubes are in an off state, and at the moment, the CH2- (1-4) provides negative high-voltage pulse information of-4V 1 to the two ends of the load RL. The circuit diagram is shown in fig. 3-3.

Negative low-voltage current:

at the time of T5-T6, the MOS tubes SH1- (5-8) and SD3-2 are in the on state, the other MOS tubes are in the off state, and at the time, the DC2 provides negative low-voltage direct current of the-DC 2 to the two ends of the load RL. The circuit diagrams are shown in fig. 3-5.

The effect is as follows:

1. the positive polarity and the negative polarity in the pulse generating circuit use the same power supply, when the mos tube is controlled to control the charging and discharging of the capacitor, signals are not delayed, and the possibility that the trailing effect may occur to pulse waveforms is reduced. And the same charging power supply can reduce the volume of the pulse generating circuit module.

2. The pulse generating device can output high-voltage pulse signals and low-voltage direct current voltage, and can continuously provide low-voltage direct current for tumor tissue loads in the gaps of the high-voltage pulse signals. When the invention is applied to tumor tissues, after irreversible electroporation ablation is carried out on high-voltage pulse, the continuous low-voltage direct current is applied to cause tumor cells to be electrolyzed, so that the tumor cells are dead, and the ablation range is enlarged.

Based on the same inventive concept, the present application proposes a pulse generating method applied to the pulse generating device described in the above embodiments, as shown in fig. 4, including:

step 401, after the first electrode of the first pulse generating circuit and the second electrode of the second pulse generating circuit are placed on the tissue to be ablated, a control signal is received.

And 402, in response to the control signal is determined to be the positive high-voltage pulse control signal, storing the positive high voltage from the high-voltage charging power supply by using the first pulse generating circuit, expanding the stored positive high voltage to a preset multiple to generate a positive high-voltage pulse signal, applying the positive high-voltage pulse signal to the tissue to be ablated through the first electrode, and simultaneously controlling the second electrode of the second pulse generating circuit to be communicated with the ground terminal.

And 403, in response to the control signal is determined to be a negative high-voltage pulse control signal, storing the negative high voltage from the high-voltage charging power supply by using the second pulse generating circuit, expanding the stored negative high voltage to a preset multiple to generate a negative high-voltage pulse signal, applying the negative high-voltage pulse signal to the tissue to be ablated through the second electrode, and simultaneously controlling the first electrode of the first pulse generating circuit to be communicated with a ground terminal.

The above steps 402 and 403 are selected and executed according to the actual control signal requirement.

In some embodiments, the pulse generation method further comprises:

step 404, in response to determining that the control signal is an anode low-voltage control signal, disconnecting the first pulse generating circuit from the high-voltage charging power supply, controlling the first low-voltage dc power supply to apply an anode low-voltage current to the tissue to be ablated through the first electrode, and simultaneously controlling the second electrode of the second pulse generating circuit to be connected to the ground.

And/or the presence of a gas in the atmosphere,

step 405, in response to determining that the control signal is a negative low-voltage control signal, disconnecting the second pulse generating circuit from the high-voltage charging power supply, controlling the second low-voltage direct-current power supply to apply a negative low-voltage current to the tissue to be ablated through the second electrode, and simultaneously controlling the first electrode of the first pulse generating circuit to be connected to a ground terminal.

In some embodiments, after said receiving the control signal, the pulse generating method further comprises:

and (3) charging process: and controlling the first switch and the third switch to be switched off, and controlling the second switch and the fourth switch to be switched on, so that the first capacitor and the second capacitor are charged by the high-voltage charging power supply.

Step 402 comprises:

and in response to the fact that the control signal is determined to be a positive high-voltage pulse control signal, the first switch and the fourth switch are controlled to be switched on, the second switch and the third switch are switched off, the first capacitor generates a positive high-voltage pulse signal from the stored positive high voltage, the positive high-voltage pulse signal is applied to the tissue to be ablated through the first electrode, and then the positive high-voltage pulse signal flows back to the ground end through the second electrode.

Step 403 comprises:

and in response to the control signal is determined to be a negative high-voltage pulse control signal, the first switch and the fourth switch are controlled to be switched off, the second switch and the third switch are switched on, the second capacitor generates a negative high-voltage pulse signal from the stored negative high voltage, the negative high-voltage pulse signal is applied to the tissue to be ablated through the second electrode, and the negative high-voltage pulse signal flows back to the grounding terminal through the first electrode.

The circuit structure used in the above process corresponds to the pulse generating device in the above embodiment, and is not described here again.

Through the above scheme, at least one of the positive electrode high voltage pulse signal, the negative electrode high voltage pulse signal, the positive electrode low voltage current and the negative electrode low voltage current can be generated correspondingly, and the various signals generated correspondingly have the same control as that of the pulse generating device in the above embodiment, and are not described again here.

Based on the same inventive concept, the present application provides an irreversible electroporation method applied to the irreversible electroporation apparatuses of the above embodiments.

As shown in fig. 5, the irreversible electroporation method includes:

step 501, generating a control signal by using a control unit, and sending the control signal to the pulse generating device.

And 502, controlling a first pulse generating circuit and a second pulse generating circuit to generate a positive electrode high-voltage pulse signal and/or a negative electrode high-voltage pulse signal to be applied to the tissue to be ablated by the pulse generating device according to the control signal.

It should be noted that the method of the embodiment of the present application may be executed by a single device, such as a computer or a server. The method of the embodiment can also be applied to a distributed scene and is completed by the mutual cooperation of a plurality of devices. In this distributed scenario, one device of the multiple devices may only perform one or more steps of the method of the embodiment of the present application, and the multiple devices interact with each other to complete the method.

It should be noted that the above describes some embodiments of the present application. Other embodiments are within the scope of the following claims. In some cases, the actions or steps recited in the claims may be performed in a different order than in the embodiments described above and still achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results. In some embodiments, multitasking and parallel processing may also be possible or may be advantageous.

Those of ordinary skill in the art will understand that: the discussion of any embodiment above is meant to be exemplary only, and is not intended to intimate that the scope of the disclosure, including the claims, is limited to these examples; within the context of the present application, technical features in the above embodiments or in different embodiments may also be combined, steps may be implemented in any order, and there are many other variations of the different aspects of the embodiments of the present application described above, which are not provided in detail for the sake of brevity.

In addition, well-known power/ground connections to Integrated Circuit (IC) chips and other components may or may not be shown in the provided figures for simplicity of illustration and discussion, and so as not to obscure the embodiments of the application. Furthermore, devices may be shown in block diagram form in order to avoid obscuring embodiments of the application, and this also takes into account the fact that specifics with respect to implementation of such block diagram devices are highly dependent upon the platform within which the embodiments of the application are to be implemented (i.e., specifics should be well within purview of one skilled in the art). Where specific details (e.g., circuits) are set forth in order to describe example embodiments of the application, it should be apparent to one skilled in the art that the embodiments of the application can be practiced without, or with variation of, these specific details. Accordingly, the description is to be regarded as illustrative instead of restrictive.

While the present application has been described in conjunction with specific embodiments thereof, many alternatives, modifications, and variations of these embodiments will be apparent to those of ordinary skill in the art in light of the foregoing description. For example, other memory architectures, such as Dynamic RAM (DRAM), may use the discussed embodiments.

The present embodiments are intended to embrace all such alternatives, modifications and variances which fall within the broad scope of the appended claims. Therefore, any omissions, modifications, substitutions, improvements, and the like that may be made without departing from the spirit and principles of the embodiments of the present application are intended to be included within the scope of the present application.

Claims (12)

1. An impulse generating device, characterized by comprising: the ablation device comprises a first pulse generating circuit and a second pulse generating circuit which share a high-voltage charging power supply, wherein the output end of the first pulse generating circuit is provided with a first electrode, the output end of the second pulse generating circuit is provided with a second electrode, and the first electrode and the second electrode are used for being arranged on tissue to be ablated;

the first pulse generating circuit is configured to store the positive high voltage sent by the high-voltage charging power supply according to the positive high-voltage pulse control signal, expand the stored positive high voltage to a preset multiple to generate a positive high-voltage pulse signal, apply the positive high-voltage pulse signal to the tissue to be ablated through the first electrode, and simultaneously control the second electrode of the second pulse generating circuit to be communicated with the ground end;

and/or the presence of a gas in the atmosphere,

the second pulse generating circuit is configured to store the negative high voltage sent by the high-voltage charging power supply according to the negative high-voltage pulse control signal, expand the stored negative high voltage to a preset multiple to generate a negative high-voltage pulse signal, apply the negative high-voltage pulse signal to a tissue to be ablated through the second electrode, and simultaneously control the first electrode of the first pulse generating circuit to be communicated with the ground terminal;

wherein the predetermined multiple is more than or equal to 1.

2. The pulse generating apparatus of claim 1, further comprising:

the first low-voltage direct-current power supply is connected with the output end of the first pulse generating circuit and is configured to disconnect the first pulse generating circuit from the high-voltage charging power supply according to a positive low-voltage direct-current control signal, control the first low-voltage direct-current power supply to apply positive low-voltage current to the tissue to be ablated through the first electrode and simultaneously control the second electrode of the second pulse generating circuit to be communicated with the ground end;

and/or the presence of a gas in the atmosphere,

and the second low-voltage direct-current power supply is connected with the output end of the second pulse generating circuit and is configured to disconnect the second pulse generating circuit from the high-voltage charging power supply according to a negative low-voltage direct-current control signal, control the second low-voltage direct-current power supply to apply negative low-voltage current to the tissue to be ablated through a second electrode and simultaneously control the first electrode of the first pulse generating circuit to be communicated with a grounding end.

3. A pulse generating device according to claim 2, wherein the positive low voltage current and/or the negative low voltage current is applied to the tissue to be ablated in the interval of the positive high voltage pulse signal and/or the negative high voltage pulse signal.

4. The pulse generating device according to claim 2 or 3, wherein the first low voltage DC power supply is connected to the output terminal of the first pulse generating circuit through a first low voltage DC power supply switch, and the first low voltage DC power supply switch is configured to be turned on after receiving the positive low voltage control signal;

the second low-voltage direct-current power supply is connected with the output end of the second pulse generation circuit through a second low-voltage direct-current power supply switch, and the second low-voltage direct-current power supply switch is configured to be switched on after receiving the negative low-voltage control signal.

5. The pulse generating apparatus of claim 1, wherein the first pulse generating circuit comprises:

at least one first diode connected with the high-voltage charging power supply;

one end of the first capacitor is connected with the first diode, and the other end of the first capacitor is connected with a grounding end;

the first switch and the second switch which are connected in series are connected with the first capacitor in parallel, and the output end of the first pulse generating circuit is arranged on a lead between the first switch and the second switch and is connected with the first electrode;

and the number of the first and second groups,

the second pulse generating circuit includes:

at least one second diode connected with the high-voltage charging power supply;

one end of the second capacitor is connected with the second diode, and the other end of the second capacitor is connected with a grounding terminal;

and the third switch and the fourth switch are connected in series and are connected with the second capacitor in parallel, and the output end of the second pulse generating circuit is arranged on a lead between the third switch and the fourth switch and is connected with the second electrode.

6. The pulse generating apparatus according to claim 5, wherein the first diodes are provided in series in at least two; the second diodes are arranged in series at least two.

7. The pulse generating device according to claim 1, wherein at least one grading circuit is further provided in parallel in the first pulse generating circuit or the second pulse generating circuit, the grading circuit being connected to the first electrode or the second electrode;

the classification circuit is configured to expand a voltage value of the positive electrode high voltage pulse signal or expand a voltage value of the negative electrode high voltage pulse signal.

8. An irreversible electroporation device, comprising:

a control unit, the pulse generating device of any one of claims 1 to 7;

the control unit is configured to control the pulse generating device to operate;

the pulse generating device is configured to control the first pulse generating circuit and the second pulse generating circuit to generate a positive electrode high-voltage pulse signal and/or a negative electrode high-voltage pulse signal to be applied to the tissue to be ablated according to the control signal of the control unit.

9. A pulse generating method applied to the pulse generating apparatus according to any one of claims 1 to 7, the pulse generating method comprising:

placing a first electrode of a first pulse generating circuit and a second electrode of a second pulse generating circuit on a tissue to be ablated, and then receiving a control signal;

in response to the fact that the control signal is determined to be a positive high-voltage pulse control signal, the first pulse generating circuit is used for storing the positive high voltage sent by the high-voltage charging power supply, the stored positive high voltage is expanded to a preset multiple to generate a positive high-voltage pulse signal, the positive high-voltage pulse signal is applied to the tissue to be ablated through the first electrode, and meanwhile the second electrode of the second pulse generating circuit is controlled to be communicated with the ground terminal;

and in response to the control signal is determined to be a negative high-voltage pulse control signal, the second pulse generating circuit is utilized to store and process the negative high voltage transmitted by the high-voltage charging power supply, the stored negative high voltage is expanded to a preset multiple to generate a negative high-voltage pulse signal, the negative high-voltage pulse signal is applied to the tissue to be ablated through the second electrode, and meanwhile, the first electrode of the first pulse generating circuit is controlled to be communicated with the ground terminal.

10. A pulse generating method according to claim 9, based on the pulse generating apparatus of claim 2, further comprising:

in response to the control signal is determined to be a positive low-voltage control signal, disconnecting the first pulse generating circuit from the high-voltage charging power supply, controlling the first low-voltage direct-current power supply to apply positive low-voltage current to the tissue to be ablated through the first electrode, and simultaneously controlling the second electrode of the second pulse generating circuit to be communicated with a ground terminal;

and/or the presence of a gas in the gas,

and in response to the fact that the control signal is determined to be a negative low-voltage control signal, disconnecting the second pulse generating circuit from the high-voltage charging power supply, controlling the second low-voltage direct-current power supply to apply negative low-voltage current to the tissue to be ablated through the second electrode, and simultaneously controlling the first electrode of the first pulse generating circuit to be communicated with a grounding end.

11. A method of pulse generation according to claim 9, wherein the pulse generation device according to claim 4;

after the receiving the control signal, further comprising:

and (3) charging process: the first switch and the third switch are controlled to be switched off, the second switch and the fourth switch are switched on, and the first capacitor and the second capacitor are charged through the high-voltage charging power supply;

the responding to the determination that the control signal is an anode high-voltage pulse control signal, storing the anode high voltage sent by the high-voltage charging power supply by using the first pulse generating circuit, expanding the stored anode high voltage to a preset multiple to generate an anode high-voltage pulse signal, applying the anode high-voltage pulse signal to the tissue to be ablated through the first electrode, and controlling the second electrode of the second pulse generating circuit to be communicated with the ground terminal includes:

in response to the control signal is determined to be a positive electrode high-voltage pulse control signal, the first switch and the fourth switch are controlled to be switched on, the second switch and the third switch are switched off, the first capacitor generates a positive electrode high-voltage pulse signal from the stored positive electrode high voltage, the positive electrode high-voltage pulse signal is applied to the tissue to be ablated through the first electrode, and then the positive electrode high-voltage pulse signal flows back to the ground terminal through the second electrode;

the responding to the determination that the control signal is a negative high-voltage pulse control signal, storing the negative high voltage from the high-voltage charging power supply by using the second pulse generating circuit, expanding the stored negative high voltage to a preset multiple to generate a negative high-voltage pulse signal, applying the negative high-voltage pulse signal to the tissue to be ablated through the second electrode, and simultaneously controlling the first electrode of the first pulse generating circuit to be communicated with the ground terminal includes:

and in response to the control signal is determined to be a negative high-voltage pulse control signal, the first switch and the fourth switch are controlled to be switched off, the second switch and the third switch are switched on, and the second capacitor applies a stored negative high-voltage generated negative high-voltage pulse signal to the tissue to be ablated through the second electrode and then flows back to the ground end through the first electrode.

12. An irreversible electroporation method to be applied to the irreversible electroporation apparatus according to claim 10, the irreversible electroporation method comprising:

generating a control signal by using a control unit, and sending the control signal to the pulse generating device;

and controlling the first pulse generating circuit and the second pulse generating circuit to generate a positive electrode high-voltage pulse signal and/or a negative electrode high-voltage pulse signal to be applied to the tissue to be ablated by the pulse generating device according to the control signal.

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