A novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation

By designing a new high-voltage pulse generator with wide and narrow pulse combination, the problems of limited tumor ablation area and complex operation in the prior art are solved, and efficient cell electroporation effect is achieved, increasing the ablation area and reducing cell survival rate.

CN113437951BActive Publication Date: 2025-07-22UNIV OF SHANGHAI FOR SCI & TECH
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Patent Information

Application Number
CN202110885515.4
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2021-08-03
Publication Date
2025-07-22
Estimated Expiration
2041-08-03

AI Technical Summary

Technical Problem

The existing cell electroporation technology has limited ablation areas during tumor ablation, complex and time-consuming operation using multiple electrodes, and lacks a pulse generator that can generate asymmetric high-frequency pulses.

Method used

A new type of high-voltage pulse generator combining wide and narrow pulses is designed, including resonant power supply, high-frequency transformer, rectifier circuit, drive control module and pulse generation circuit. Through resonant charging and high-frequency transformer boost, high-voltage narrow pulses and low-voltage wide pulses can be output. The FPGA control module is used to change the working mode and simplify the control process.

Benefits of technology

It improves charging efficiency, has a high output voltage amplitude, and can output high-voltage narrow pulses and low-voltage wide pulses at the same time, which increases the cell ablation area, reduces cell survival rate, and simplifies the operation process.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention provides a novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation, which includes a resonant power supply, a high-frequency transformer, a rectifying circuit, a drive control module, and a pulse generating circuit. Due to the use of the resonant charging method, the charging efficiency is improved compared with traditional cell electroporation power supplies; due to the presence of the high-frequency transformer, the output voltage amplitude is high; and due to the drive control module being able to change the working mode of the pulse generating circuit, this high-voltage pulse generator can output high-voltage narrow pulses and low-voltage wide pulses simultaneously. When applied to cell electroporation, compared with pulse generators that only use high-voltage narrow pulses or low-voltage wide pulses, the effect of this high-voltage pulse generator greatly reduces the cell survival rate and increases the cell ablation area. In addition, the high-voltage pulse generator of the present invention also has the advantages of simple control and compact structure.
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Description

Technical Field

[0001] The present invention belongs to the technical field of pulsed power, and particularly relates to a novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation. Background Art

[0002] Electroporation has been widely used to increase cell membrane permeability by using high-voltage pulsed electric fields. After an electric pulse, the pores on the cell membrane may last from several seconds to several minutes, and the cells survive, which is called reversible electroporation. This process can be used to achieve intracellular uptake of various molecules, electrofusion, and nanoelectroporation. If a stronger electric pulse acts on the cell membrane, the pores may become too large to recover, causing irreversible damage to the cell membrane and resulting in cell death. This phenomenon is called irreversible electroporation (IRE), and IRE is widely used in technologies such as bacterial inactivation, tumor ablation, and food processing.

[0003] The pulsed power supply has been applied to cell irreversible electroporation for a long time. Irreversible electroporation (IRE) uses pulsed electric fields to destroy cell membranes for cell tumor ablation. Although relatively good preliminary clinical results have been achieved, due to the limitation of the ablation area, the actual effect is not ideal.

[0004] Satisfactory clinical results have been achieved using the IRE technique, but the treatment is limited to tumor cells smaller than 3 cm, and the treatment effect decreases as the size of the tumor cells increases. See 《Optimization of Irreversible Electroporation Protocols for In-Vivo Myocardial Decellularization》 and 《Thermal Energy during Irreversible Electroporation and the Influence of Different Ablation Parameters》. When using the IRE technique, by changing the pulse parameters, such as the applied pulse voltage, pulse width, number of pulses, etc., the affected area can be increased. In addition, the affected area can also be increased by using multiple electrodes acting on the tumor cells simultaneously. However, using multiple electrodes makes the control program complex and increases the experimental operation time. See 《Irreversible electroporation for nonthermal tumor ablation in the clinical setting: a systematic review of safety and efficacy》 and 《Irreversible electroporation for nonthermal tumor ablation in the clinical setting: a systematic review of safety and efficacy》. Therefore, some researchers are committed to expanding the ablation area by using an electric pulse with two needle electrodes. Rubinsky et al. showed that combining pulsed electroporation with DC current produces a larger tissue ablation area. See 《Synergistic Combination of Electrolysis and Electroporation for Tissue Ablation》 and 《Tissue Ablation by a Synergistic Combination of Electroporation and Electrolysis Delivered by a Single Pulse》.Ivey et al. found that compared with using traditional IRE to eliminate tumor cells, using high-frequency IRE can eliminate a larger area of tumor cells. See "Targeted Cellular Ablation Based On the Morphology of Malignant Cells". In addition, Sano et al. found that compared with symmetric high-frequency IRE, using asymmetric high-frequency IRE produces a larger ablation area. See "Asymmetric Waveforms Decrease Lethal Thresholds in High-Frequency Irreversible Electroporation Therapies". However, there is currently a lack of a pulse generator that can generate asymmetric high-frequency pulses and is applicable to cell electroporation. Summary of the Invention

[0005] The present invention is made to solve the above problems, and aims to provide a novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation. The present invention adopts the following technical solutions:

[0006] The present invention provides a novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation, which is characterized by comprising: a resonant power supply; a high-frequency transformer for boosting and isolating the resonant power supply to obtain high-voltage alternating current; a rectifying circuit for converting the high-voltage alternating current into high-voltage direct current; a pulse generating circuit for generating square-wave pulses with specific voltage amplitude and voltage pulse width; and a drive control module for changing the working mode of the pulse generating circuit so that the pulse generating circuit outputs high-voltage narrow square-wave pulses and low-voltage wide square-wave pulses simultaneously. Among them, the resonant power supply is electrically connected to the primary side of the high-frequency transformer, the secondary side of the high-frequency transformer is electrically connected to the rectifying circuit, the rectifying circuit is electrically connected to the pulse generating circuit, and the drive control module is electrically connected to the pulse generating circuit.

[0007] The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation provided by the present invention may also have the following technical feature, wherein the pulse generating circuit has a storage capacitor, and square-wave pulses are generated through the charging and discharging of the storage capacitor.

[0008] The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation provided by the present invention may also have the following technical feature, wherein the high-frequency transformer has a coil, the pulse generating circuit has a semiconductor switch, the voltage amplitude is adjusted by changing the turns ratio of the coil, and is also adjusted by increasing or decreasing the number of circuit stages of the high-frequency transformer, and the voltage pulse width is adjusted by the on-time of the drive signal of the semiconductor switch.

[0009] The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation provided by the present invention may also have the following technical features, wherein the drive control module adopts a fiber-optic isolation synchronous drive mode.

[0010] The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation provided by the present invention may also have the following technical features, wherein the control signal of the drive control module is provided by an FPGA.

[0011] The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation provided by the present invention may also have the following technical features, wherein the pulse generation circuit includes at least two energy storage capacitors.

[0012] The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation provided by the present invention may also have the following technical features, wherein the voltage amplitude of the high-voltage narrow square-wave pulse is 2200V, and the voltage pulse width of the high-voltage narrow square-wave pulse is 1μ S , the voltage amplitude of the low-voltage wide square-wave pulse is 200V, and the voltage pulse width of the low-voltage wide square-wave pulse is 50μ S .

[0013] Functions and effects of the invention

[0014] The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation according to the present invention includes a resonant power supply, a high-frequency transformer, a rectifier circuit, a drive control module, and a pulse generation circuit. Due to the use of the resonant charging method, the charging efficiency is improved compared with the traditional cell electroporation power supply; due to the presence of the high-frequency transformer, the output voltage amplitude is high, and the output voltage can be adjusted by changing the turns ratio of the transformer coil and increasing or decreasing the number of circuit stages; since the drive control module can change the working mode of the pulse generation circuit, the high-voltage pulse generator can output both high-voltage narrow pulses and low-voltage wide pulses. When applied to cell electroporation, multiple electrodes are not required. Moreover, compared with the pulse generators that only use high-voltage narrow pulses or low-voltage wide pulses, the high-voltage pulse generator of the present invention greatly reduces the cell survival rate and increases the cell ablation area. In addition, the high-voltage pulse generator of the present invention also has the advantages of simple control and compact structure. Description of the drawings

[0015] Figure 1 is the overall framework diagram of the high-voltage pulse generator in the embodiment of the present invention;

[0016] Figure 2 is the circuit diagram of the high-voltage pulse generator in the embodiment of the present invention;

[0017] Figure 3 is the circuit diagram of the two-stage pulse generation circuit in the embodiment of the present invention;

[0018] Figure 4 It is a schematic diagram of high-voltage narrow-pulse discharge in an embodiment of the present invention;

[0019] Figure 5 It is a schematic diagram of low-voltage wide-pulse discharge in an embodiment of the present invention;

[0020] Figure 6 It is a schematic diagram of the output waveform of the pulse generation circuit in an embodiment of the present invention. Detailed implementation manners

[0021] In order to make the technical means, creative features, achieved purposes and effects of the present invention easy to understand, the following specifically describes the novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation of the present invention in conjunction with embodiments and drawings.

[0022] <Embodiment>

[0023] Figure 1 It is the overall framework diagram of the high-voltage pulse generator in an embodiment of the present invention.

[0024] As Figure 1 shown, the novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation includes industrial-frequency rectifier circuits 1 and 5, resonant power supplies 2 and 6, high-frequency transformers 3 and 7, rectifier circuits 4 and 8, FPGA 9, drive control module 10, and pulse generation circuit 11.

[0025] Among them, the industrial-frequency rectifier circuit 1, resonant power supply 2, high-frequency transformer 3, rectifier circuit 4, pulse generation circuit 11, FPGA 9, and drive control module 10 constitute the first pulse generator; the industrial-frequency rectifier circuit 5, resonant power supply 6, high-frequency transformer 7, rectifier circuit 8, pulse generation circuit 11, FPGA 9, and drive control module 10 constitute the second pulse generator.

[0026] The industrial-frequency rectifier circuits 1 and 5 are respectively electrically connected to the resonant power supplies 2 and 6, and are used for rectifying and filtering the resonant power supplies 2 and 6.

[0027] The high-frequency transformers 3 and 7 are used for boosting and isolating the resonant power supplies 2 and 6, so as to obtain high-voltage alternating current output. The primary sides of the high-frequency transformers 3 and 7 are respectively electrically connected to the resonant power supplies 2 and 6, and the secondary sides of the high-frequency transformers 3 and 7 are respectively electrically connected to the rectifier circuits 4 and 8.

[0028] The rectifier circuits 4 and 8 are used for converting the high-voltage alternating current output by the high-frequency transformers 3 and 7 into high-voltage direct current.

[0029] The FPGA 9 is used to provide control signals to the drive control module 10.

[0030] The drive control module 10 is used to change the working mode of the pulse generation circuit 11, so that the pulse generation circuit 11 can output high-voltage narrow square-wave pulses and low-voltage wide square-wave pulses simultaneously.

[0031] The pulse generation circuit 11 is used to generate square-wave pulses with specific voltage amplitudes and voltage pulse widths. The working modes of the pulse generation circuit 11 include a high-voltage narrow pulse mode and a low-voltage wide pulse mode.

[0032] Figure 2 It is the circuit diagram of the high-voltage pulse generator in the embodiment of the present invention.

[0033] Taking the first-channel pulse generator as an example, as Figure 2 shown, each of the industrial-frequency rectification circuits 1 includes industrial-frequency rectification diodes V1, V2, V3, V4 and a DC-blocking capacitor C5.

[0034] The series-connected industrial-frequency rectification diodes V1 and V2 are in parallel with the series-connected industrial-frequency rectification diodes V3 and V4. After being connected in parallel, they are then connected in parallel with the DC-blocking capacitor C5. Both ends of the DC-blocking capacitor C5 are connected to the primary side of the high-frequency transformer 3; one end of the resonant power supply 2 is connected between the industrial-frequency rectification diodes V1 and V2, and the other end of the resonant power supply 2 is connected between the industrial-frequency rectification diodes V3 and V4.

[0035] The high-frequency transformer 3 includes a resonant capacitor Cr, a resonant inductor Lr, semiconductor switches T5, T6, T7, T8, a coil N1 and a coil N2. Among them, the semiconductor switches T5, T6, T7, T8 are MOSFETs.

[0036] The series-connected semiconductor switches T5 and T6 are in parallel with the series-connected semiconductor switches T7 and T8; one end of the resonant capacitor Cr is connected between the semiconductor switches T5 and T6, and the other end of the resonant capacitor Cr is connected to the coil N2; one end of the resonant inductor Lr is connected between the semiconductor switches T7 and T8, and the other end of the resonant inductor Lr is connected to the coil N1.

[0037] The rectification circuit 4 includes a rectifier bridge V5, V6.

[0038] The input end of the rectifier bridge V5 is connected to the coil N1, and the output end of the rectifier bridge V5 is connected to both ends of the energy storage capacitor C1, that is, connected to the pulse generation circuit 11; the input end of the rectifier bridge V6 is connected to the coil N2, and the output end of the rectifier bridge V6 is connected to both ends of the energy storage capacitor C3, that is, connected to the pulse generation circuit 11.

[0039] In the second path pulse generator, the structures and working principles of the power frequency rectification circuit 5, the high-frequency transformer 7, and the rectification circuit 8 are respectively the same as those of the power frequency rectification circuit 1, the high-frequency transformer 3, and the rectification circuit 4 in the first path pulse generator, and will not be elaborated here.

[0040] Figure 3 It is the circuit diagram of the two-stage pulse generation circuit in the embodiment of the present invention.

[0041] As Figure 3 shown, the pulse generation circuit 11 is composed of a high-voltage pulse generation circuit and a low-voltage pulse generation circuit that are superimposed on each other.

[0042] The pulse generation circuit 11 includes energy storage capacitors C1, C2, C3, C4, semiconductor switches S1, S2, S3, S4, diodes D1, D2, D3, D4, D5, D6, and a load Rf. Among them, the semiconductor switches S1, S2, S3, S4 are MOSFTs, and the load Rf is a resistive load of 100Ω.

[0043] The positive electrode of the energy storage capacitor C1 is connected to the negative electrode of the energy storage capacitor C2, and the negative electrode of the energy storage capacitor C1 is connected to one end of the load Rf; the positive electrode of the energy storage capacitor C2 is connected to one end of the semiconductor switch S1; the other end of the semiconductor switch S1 is connected to the anode of the diode D1; after the energy storage capacitor C2, the semiconductor switch S1, and the diode D1 are connected in series and then connected in parallel with the diode D2, the anode of the diode D2 is connected to the negative electrode of the energy storage capacitor C2, and the cathode of the diode D2 is connected to the cathode of the diode D1; the cathode of the diode D1 is connected to one end of the semiconductor switch S2; the other end of the semiconductor switch S2 is connected to the anode of the diode D4; the cathode of the diode D4 is connected to the negative electrode of the energy storage capacitor C3; after the semiconductor switch S2, the diode D4, and the energy storage capacitor C3 are connected in series and then connected in parallel with the diode D3, the anode of the diode D3 is connected to one end of the semiconductor switch S2, and the cathode of the diode D3 is connected to the positive electrode of the energy storage capacitor C3; the positive electrode of the energy storage capacitor C3 is connected to the negative electrode of the energy storage capacitor C4; the positive electrode of the energy storage capacitor C4 is connected to one end of the semiconductor switch S3; the other end of the semiconductor switch S3 is connected to the anode of the diode D5; one end of the semiconductor switch S4 is connected to the negative electrode of the energy storage capacitor C4, and the other end of the semiconductor switch S4 is connected to the anode of the diode D6; the cathode of the diode D6 is connected to the cathode of the diode D5; after the energy storage capacitor C4, the semiconductor switch S3, and the diode D5 are connected in series and then connected in parallel with the series-connected semiconductor switch S4 and diode D6, and then connected to the other end of the load Rf.

[0044] The control signal of the drive control module 10 is provided by the FPGA 9, and the drive control module 10 changes the working mode of the pulse generation circuit 11 by controlling the semiconductor switches S1, S2, S3, S4.

[0045] In this embodiment, first, the operating frequencies of the resonant power supplies 2 and 5 are adjusted so that the resonant power supplies 2 and 5 operate in a resonant state. The outputs of the resonant power supplies 2 and 5 are respectively used as the primary sides of the high-frequency transformers 3 and 7. The high-frequency transformers 3 and 7 are used for boosting and isolation. The secondary sides of the high-frequency transformers 3 and 7 are connected to the rectifier circuits 4 and 8, and the output current directions are changed through the rectifier bridges V5, V6, V7, and V8.

[0046] Since the turns ratios of the coils of the high-frequency transformer 3 are different from those of the high-frequency transformer 7, the voltage values on the energy storage capacitors adjacent to each pole are different. For example, the voltage value on the energy storage capacitor C2 is higher than that on the energy storage capacitor C1, while the capacitance value of the energy storage capacitor C1 is much larger than that of the energy storage capacitor C2. At the same time, the FPGA 9 generates multiple delay signals, and the drive control module 10 controls the on-off of the semiconductor switches S1, S2, S3, and S4 through these multiple delay signals, thereby realizing isolation drive and enabling the pulse generation circuit 11 to generate high-voltage narrow square-wave pulses and low-voltage wide square-wave pulses simultaneously.

[0047] The working processes of the pulse generation circuit 11 in two working modes will be specifically described below in conjunction with the accompanying drawings.

[0048] Figure 4 It is a schematic diagram of high-voltage narrow-pulse discharge in an embodiment of the present invention.

[0049] As Figure 4 shown by the arrow direction in [Figure], when the pulse generation circuit 11 operates in the high-voltage narrow-pulse mode, the drive control module 10 controls the semiconductor switches S1, S2, and S3 to turn on. At this time, the diode D2 bears the reverse voltage of the energy storage capacitor C2, and the diode D3 bears the reverse voltage of the energy storage capacitor C3. Therefore, both the diodes D2 and D3 are not turned on, while the diodes D1, D4, and D5 are turned on. The sequentially connected energy storage capacitor C1, energy storage capacitor C2, semiconductor switch S1, semiconductor switch S1, energy storage capacitor C3, energy storage capacitor C4, semiconductor switch S3, and load Rf form a series circuit, and the energy storage capacitors C1, C2, C3, and C4 discharge to the load Rf. Since all the energy storage capacitors in the pulse generation circuit 11 are connected in series for discharge at this time, a relatively high voltage value is obtained on the load Rf. At this time, the pulse generation circuit 11 outputs high-voltage narrow square-wave pulses.

[0050] Figure 5 It is a schematic diagram of low-voltage wide-pulse discharge in an embodiment of the present invention.

[0051] As Figure 5As shown by the arrow direction in the figure, when the pulse generation circuit 11 operates in the low-voltage wide-pulse mode, the drive control module 10 controls the semiconductor switches S1 and S3 to turn off, and controls the semiconductor switches S2 and S4 to turn on. At this time, the diode D3 bears the reverse voltage of the energy storage capacitor C3, so the diode D3 does not conduct, while the diodes D2, D4, and D6 conduct. The energy storage capacitor C1, semiconductor switch S2, energy storage capacitor C3, semiconductor switch S4, and load Rf connected in sequence form a series circuit, and the energy storage capacitors C1 and C3 discharge to the load Rf. Since the energy storage capacitors with lower voltages in the pulse generation circuit 11 discharge in series at this time, a low voltage value is obtained on the load Rf. At this time, the pulse generation circuit 11 outputs a low-voltage wide square-wave pulse.

[0052] Figure 6 It is a schematic diagram of the output waveform of the pulse generation circuit in the embodiment of the present invention.

[0053] As Figure 6 shown, the novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation can output a high-voltage narrow square-wave pulse and a low-voltage wide square-wave pulse simultaneously. The voltage amplitude of the high-voltage narrow square-wave pulse is 2200V, and its voltage pulse width is 1μ S s; the voltage amplitude of the low-voltage wide square-wave pulse is 200V, and its voltage pulse width is 50μ S s.

[0054] In this embodiment, the novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation can adjust the output voltage amplitude by changing the turns ratio of multiple coils of the high-frequency transformers 3 and 7, and can also adjust the voltage amplitude by increasing or decreasing the number of circuit stages of the high-frequency transformers 3 and 7. At the same time, the high-voltage pulse generator can adjust the pulse width of the output voltage by changing the turn-on time of the drive signals of the semiconductor switches S1, S2, S3, and S4.

[0055] Functions and effects of the embodiment

[0056] A novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation provided by this embodiment includes power frequency rectifier circuits 1 and 5, resonant power supplies 2 and 4, high-frequency transformers 3 and 7, rectifier circuits 4 and 8, an FPGA 9, a drive control module 10, and a pulse generation circuit 11. Due to the use of the resonant charging method, the charging efficiency is improved compared with traditional cell electroporation power supplies; due to the presence of high-frequency transformers 3 and 7, the output voltage amplitude is high; since the drive control module 10 can change the working mode of the pulse generation circuit 11, this high-voltage pulse generator can output high-voltage narrow pulses and low-voltage wide pulses simultaneously. When applied to cell electroporation, multiple electrodes are not required. Moreover, compared with pulse generators that only use high-voltage narrow pulses or low-voltage wide pulses, the effect of this high-voltage pulse generator greatly reduces the cell survival rate and increases the cell ablation area. In addition, the high-voltage pulse generator of the present invention also has the advantages of simple control and compact structure.

[0057] Furthermore, since the high-frequency transformers 3 and 7 have coils, the voltage amplitude of the output square-wave pulse can be adjusted by changing the turns ratio of the coils; since the pulse generation circuit 11 has semiconductor switches S1, S2, S3, and S4 controlled by the drive control module 10, the voltage pulse width of the output square-wave pulse can be adjusted by changing the turn-on time of the drive signals of the semiconductor switches S1, S2, S3, and S4.

[0058] The above embodiments are only used to illustrate the specific implementation manners of the present invention, and the present invention is not limited to the description scope of the above embodiments.

Claims

1. A novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation, characterized in that, Comprising: A resonant power supply; A high-frequency transformer for boosting and isolating the resonant power supply to obtain high-voltage alternating current; A rectification circuit for converting the high-voltage alternating current into high-voltage direct current; A pulse generation circuit for generating a square-wave pulse with a specific voltage amplitude and voltage pulse width; And A drive control module for enabling the pulse generation circuit to output a high-voltage narrow square-wave pulse and a low-voltage wide square-wave pulse simultaneously, adopting a synchronous drive method with optical fiber isolation, wherein, the resonant power supply is electrically connected to the primary side of the high-frequency transformer, the secondary side of the high-frequency transformer is electrically connected to the rectification circuit, the rectification circuit is electrically connected to the pulse generation circuit, the drive control module is electrically connected to the pulse generation circuit, The pulse generating circuit includes energy storage capacitors C1, C2, C3, C4, semiconductor switches S1, S2, S3, S4, diodes D1, D2, D3, D4, D5, D6, and a load R f , the positive electrode of the energy storage capacitor C1 is connected to the negative electrode of the energy storage capacitor C2, and the negative electrode of the energy storage capacitor C1 is connected to one end of the load Rf; the positive electrode of the energy storage capacitor C2 is connected to one end of the semiconductor switch S1; the other end of the semiconductor switch S1 is connected to the anode of the diode D1; after the energy storage capacitor C2, the semiconductor switch S1, and the diode D1 are connected in series, they are connected in parallel with the diode D2. The anode of the diode D2 is connected to the negative electrode of the energy storage capacitor C2, and the cathode of the diode D2 is connected to the cathode of the diode D1; the cathode of the diode D1 is connected to one end of the semiconductor switch S2; the other end of the semiconductor switch S2 is connected to the anode of the diode D4; the cathode of the diode D4 is connected to the negative electrode of the energy storage capacitor C3; after the semiconductor switch S2, the diode D4, and the energy storage capacitor C3 are connected in series, they are connected in parallel with the diode D3. The anode of the diode D3 is connected to one end of the semiconductor switch S2, and the cathode of the diode D3 is connected to the positive electrode of the energy storage capacitor C3; the positive electrode of the energy storage capacitor C3 is connected to the negative electrode of the energy storage capacitor C4; the positive electrode of the energy storage capacitor C4 is connected to one end of the semiconductor switch S3; the other end of the semiconductor switch S3 is connected to the anode of the diode D5; one end of the semiconductor switch S4 is connected to the negative electrode of the energy storage capacitor C4, and the other end of the semiconductor switch S4 is connected to the anode of the diode D6; the cathode of the diode D6 is connected to the cathode of the diode D5; the energy storage capacitor C4, the semiconductor switch S3, and the diode D5 are connected in series and then connected in parallel with the series-connected semiconductor switch S4 and the diode D6, and after being connected in parallel, they are connected to the other end of the load Rf, the pulse generation circuit generates the square-wave pulse through the charge and discharge of the energy storage capacitor.

2. The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation according to claim 1, characterized in that: Among them, The high-frequency transformer has multiple coils, the voltage amplitude is adjusted by changing the turn ratio of the multiple coils and by increasing or decreasing the number of circuit stages of the high-frequency transformer, the voltage pulse width is adjusted by the on-time of the drive signal of the semiconductor switch.

3. The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation according to claim 1, characterized in that: Among them, The control signal of the drive control module is provided by an FPGA.

4. The novel high-voltage pulse generator combining wide and narrow pulses for cell electroporation according to claim 1, characterized in that: Among them, The voltage amplitude of the high-voltage narrow square-wave pulse is 2200V, and the voltage pulse width of the high-voltage narrow square-wave pulse is 1μ S , The voltage amplitude of the low-voltage wide square wave pulse is 200V, and the voltage pulse width of the low-voltage wide square wave pulse is 50μ S .

Citation Information

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