CN117958948A - High-frequency bidirectional irreversible electroporation pulse system - Google Patents
High-frequency bidirectional irreversible electroporation pulse system Download PDFInfo
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- A61B2018/00613—Irreversible electroporation
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Abstract
The invention discloses a high-frequency bidirectional irreversible electroporation pulse system, which comprises an upper-layer information management device, a lower computer control device and a bidirectional high-voltage pulse discharge main loop, wherein the upper-layer information management device is connected with the lower computer control device; the upper information management device sets working parameters of the bidirectional high-voltage pulse discharge main loop and transmits the working parameters to the lower computer control device; the lower computer control device receives the working parameters set by the upper information management device, generates control signals and transmits the control signals to the bidirectional high-voltage pulse discharge main loop; the bidirectional high-voltage pulse discharge main loop receives the control signal, generates a high-frequency bidirectional irreversible electroporation pulse signal, and returns a feedback signal to the upper-layer information management device. The invention can better and more uniformly increase the induced transmembrane potential of the closely arranged cells to the simulated electroporation threshold, thereby ensuring that the ablation area is more uniform.
Description
Technical Field
The invention relates to the technical field of electroporation equipment, in particular to a high-frequency bidirectional irreversible electroporation pulse system.
Background
Tumors are a common disease and frequently encountered disease, wherein malignant tumors are the most serious disease which endangers human health at present. Since the pathogenesis and etiology of malignant tumors is not fully understood, there is a lack of fundamental precautions. To date, humans have not been able to cure malignant tumors as much as other common frequently encountered diseases. Because of the intractability of malignant tumors, various nationalities have treated malignant tumors for centuries by combining surgery and radiotherapy and chemotherapy to obtain a longer survival period. But radiotherapy and chemotherapy have great influence on human immunity and seriously affect the quality of life.
Irreversible electroporation (IrreversibleElectroporation, IRE) is an emerging non-thermal ablation technique for treating tumors. The method uses microsecond-level high-voltage discharge pulse to form nanoscale pores on the cell membrane of the acted cell, so as to change the permeability of the cell membrane, break the internal balance of the cell and further cause apoptosis, and the process is called irreversible electroporation. A typical treatment for irreversible electroporation is a square wave pulse with a voltage of 1500v/cm and a pulse width of 50-100. Mu.s, the number of pulses being 70-100, which is unidirectionally transmitted between two electrode needles. The number of electrodes, the electrode spacing and the electrode exposure length can be adjusted according to the size and shape of the tumor during the treatment process. When IRE is used, most importantly, the electric field can damage cell membranes and simultaneously can not cause thermal effect, so that the tissue is damaged, and the IRE has wide application prospect in clinic, especially for lesions close to important blood vessels and nerves, minimally invasive ablation can be performed, and the safety of treatment is improved.
Although IRE has good prospect in clinic, the prior irreversible electroporation adopts unipolar high-voltage discharge pulse to act on cells, when the technology is used for irreversibly ablating tumor cells of a human body, the muscle of a patient can be greatly twitched at the moment of pulse discharge, the limb of the patient is induced to be greatly moved, and the position fixing and treatment effect of a discharge electrode are seriously affected. Therefore, the current practice of such procedures requires tracheal intubation, general anesthesia, muscle relaxant injection and ventilator assistance, and cannot be performed under local anesthesia as conveniently as most of the interventional minimally invasive procedures currently used in clinic, which is cumbersome and costly, increases the complexity and risk of ablation procedures, and may cause complications, thus limiting the application and popularization of the technique.
Disclosure of Invention
In view of the above, an object of the embodiments of the present invention is to provide a high-frequency bidirectional irreversible electroporation pulse system, which can better and more uniformly increase the induced transmembrane potential of closely arranged cells to the threshold of simulated electroporation, so that the ablation area is more uniform.
In a preferred embodiment of the present invention, the high-frequency bi-directional irreversible electroporation pulse system includes an upper information management device, a lower computer control device and a bi-directional high-voltage pulse discharge main circuit.
The upper information management device sets working parameters of the bidirectional high-voltage pulse discharge main loop and transmits the working parameters to the lower computer control device.
The lower computer control device receives the working parameters set by the upper information management device, generates control signals and transmits the control signals to the bidirectional high-voltage pulse discharge main loop.
The bidirectional high-voltage pulse discharge main loop receives the control signal, generates a high-frequency bidirectional irreversible electroporation pulse signal, and returns a feedback signal to the upper-layer information management device.
In a preferred embodiment of the present invention, the upper layer information management device of the high-frequency bidirectional irreversible electroporation pulse system includes a parameter setting module, a coding signal generating module, a feedback signal receiving module and a parameter transmitting module.
The parameter setting module performs data interaction with a user or input equipment, and inputs working parameters, wherein the working parameters comprise at least one of pulse frequency, pulse amplitude, pulse width, pulse shape, pulse interval, pulse lifting time, pulse repetition number and pulse mode.
The coding signal generation module processes, verifies, codes and format conversion on the working parameters to generate coding signals, and the coding signals adjust the working state of the bidirectional high-voltage pulse discharge main loop.
And the parameter transmission module transmits the encoded signal to the lower computer control device.
The feedback signal receiving module receives the feedback signal returned by the bidirectional high-voltage pulse discharging main loop, analyzes and processes the feedback signal, and transmits the feedback signal to the coding signal generating module to generate a coding signal.
In a preferred embodiment of the present invention, the lower computer control device of the above-mentioned high-frequency bidirectional irreversible electroporation pulse system includes a high-frequency bidirectional pulse generation control module, a time sequence function control module, an energy storage control module and a pH control module.
The high-frequency bidirectional pulse generation control module receives the working parameters and the feedback signals, analyzes and processes the working parameters and the feedback signals, and generates the control signals.
The time sequence function control module controls the starting time of charging and discharging and the duration time of charging and discharging.
The energy storage module receives, stores and releases electrical power, providing a power supply.
The energy storage control module monitors the residual capacity of the energy storage module, and adjusts the duration and the intensity of the high-frequency bidirectional irreversible electroporation pulse signal according to the change of the residual capacity.
The pH control module receives a pH measured value of the tissue to be detected, and adjusts the duration and the intensity of the high-frequency bidirectional irreversible electroporation pulse signal according to the pH measured value.
In a preferred embodiment of the present invention, the energy storage control module of the high-frequency bidirectional irreversible electroporation pulse system includes:
And the capacitance sensor is used for collecting capacitance data and monitoring the capacitance in the energy storage module in real time.
And the energy storage comparison processing unit is used for comparing the current capacitance with a preset capacitance threshold.
And the energy storage parameter adjusting unit is used for controlling the output end of the bidirectional high-voltage pulse discharge main loop to stop outputting when the current capacitance is lower than a preset capacitance threshold value, and adjusting the pulse width of the high-frequency bidirectional irreversible electroporation pulse signal based on the current capacitance when the current capacitance is higher than the preset capacitance threshold value.
And the capacitance sensor driving unit is used for driving and controlling the capacitance sensor to monitor the capacitance of the energy storage module in real time.
And the energy storage signal driving unit drives the high-frequency bidirectional pulse generation control module and the time sequence function control module to realize real-time adjustment of parameters according to the adjustment signals of the energy storage parameter adjustment unit.
And the energy storage integrated MCU unit coordinates functions among the capacitance sensor, the energy storage comparison processing unit, the energy storage parameter adjusting unit, the capacitance sensor driving unit and the energy storage signal driving unit.
The technical effects are as follows: the capacitance is managed and controlled by monitoring and adjusting the capacitance in real time, so that overload and damage of an energy storage module are avoided, high-efficiency utilization and storage of energy are ensured, and the energy utilization rate of the system is improved; by controlling and adjusting the output of the pulse signals, the stable working state of the system is maintained, the system faults and instability are reduced, the requirements of different experiments or applications are met, and greater flexibility and adjustability are provided.
In a preferred embodiment of the present invention, the pH control module of the above-mentioned high-frequency bi-directional irreversible electroporation pulse system comprises:
and the pH value acquisition unit drives the pH sensor to acquire pH value data of the electrolysis product close to the electrode.
And the pH comparison processing unit is used for comparing the current pH value with a preset pH threshold value.
The pH parameter adjusting unit is used for shortening the pulse duration time, reducing the pulse intensity when the current pH value is within the preset pH range, prolonging the pulse duration time and increasing the pulse intensity when the current pH value is not within the preset pH range.
And the pH sensor driving unit is used for driving and controlling the pH sensor to monitor the pH value of the electrolysis product close to the electrode in real time.
And the pH signal driving unit drives the high-frequency bidirectional pulse generation control module and the time sequence function control module to realize real-time adjustment of parameters according to the adjustment signal of the pH parameter adjustment unit.
And the pH integrated MCU unit coordinates functions among the pH value acquisition unit, the pH comparison processing unit, the pH parameter adjustment unit, the pH sensor driving unit, the pH signal driving unit and the pH signal driving unit.
The technical effects are as follows: the system can adapt to different pH conditions more quickly, and ensures the stability and reliability of the high-frequency bidirectional irreversible electroporation pulse system under different pH conditions.
In a preferred embodiment of the present invention, the lower computer control device of the high-frequency bidirectional irreversible electroporation pulse system further includes a first photoelectric isolation module and a second photoelectric isolation module.
The first photoelectric isolation module performs photoelectric isolation on the control signal.
The second photoelectric isolation module performs photoelectric isolation on the feedback signal.
In a preferred embodiment of the present invention, each of the optoelectronic isolation modules of the high frequency bi-directional irreversible electroporation pulse system comprises:
and the photoelectric driving circuit receives an input signal and converts the input signal into an input current and/or an input voltage, wherein the input signal comprises the control signal or the feedback signal.
And the light emitting diode receives the input current and/or the input voltage and generates an optical signal.
And the phototriode receives the optical signal and converts the optical signal into an output signal.
In a preferred embodiment of the present invention, the lower computer control device of the high-frequency bidirectional irreversible electroporation pulse system further includes a power amplification circuit for amplifying the power of the control signal.
In a preferred embodiment of the present invention, the power amplifying circuit of the high-frequency bi-directional irreversible electroporation pulse system comprises:
and the control signal input interface is used for receiving the control signal and carrying out impedance matching and protection on the control signal.
And the power driving circuit receives the control signal transmitted by the control signal input interface and generates a current and/or voltage signal.
And the power amplifier is used for receiving the current and/or voltage signals generated by the power driving circuit and amplifying the power.
The technical effects are as follows: the control signal from the control signal source is amplified to a sufficient power level by signal amplification and power supply to drive the bi-directional high voltage pulse discharge main loop to generate a high frequency bi-directional irreversible electroporation pulse signal.
In a preferred embodiment of the present invention, the lower computer control device of the above-mentioned high-frequency bidirectional irreversible electroporation pulse system further includes a voltage and current detection circuit, which receives the feedback signal of the bidirectional high-voltage pulse discharge main loop, detects the charging voltage, the discharging voltage and the discharging current, and uploads the detection result to the upper information management device.
In a preferred embodiment of the present invention, the voltage and current detection circuit of the high-frequency bidirectional irreversible electroporation pulse system includes:
a voltage-current sensor converts voltage and/or current signals into measurable electrical signals.
And the signal conditioning circuit is used for amplifying, filtering and linearizing the measurable electric signal to obtain an analog voltage and/or current signal.
An ADC analog-to-digital converter converts the analog voltage and/or current signals to digital voltage and/or current signals.
And the digital processing circuit is used for processing, decoding and checking the digital voltage and/or current signals.
The technical effects are as follows: through the voltage and current detection circuit, the system can monitor and control the voltage and current parameters of the high-frequency bidirectional irreversible electroporation pulse in real time.
In a preferred embodiment of the present invention, the lower computer control device of the high-frequency bidirectional irreversible electroporation pulse system further includes a signal filtering module, and performs filtering processing on the feedback signal.
In a preferred embodiment of the present invention, the signal filtering module of the high-frequency bidirectional irreversible electroporation pulse system includes:
And the operational amplifier amplifies the feedback signal.
And a capacitor for performing frequency selection for amplifying the feedback signal.
The technical effects are as follows: by selecting proper filter types and parameters, the signal filtering module can realize the filtering function of the feedback signal, remove noise and unnecessary frequency components and extract the needed effective information.
In a preferred embodiment of the present invention, the bidirectional high-voltage pulse discharging main circuit of the high-frequency bidirectional irreversible electroporation pulse system includes a charging power supply U1, an energy storage capacitor set, a fast electronic switch and a discharging electrode.
And a charging switch is arranged between the charging power supply U1 and the energy storage capacitor group.
The energy storage capacitor group is connected with the discharge electrode through the fast electronic switch.
And a discharge switch is arranged between the fast electronic switch and the discharge electrode.
In a preferred embodiment of the present invention, the energy storage capacitor set of the high-frequency bidirectional irreversible electroporation pulse system includes a large-capacity capacitor set and a small-capacity capacitor set connected in parallel.
The high-capacity capacitor group comprises one high-capacity capacitor or a plurality of high-capacity capacitors which are connected in series.
The small-capacity capacitor comprises a small-capacity capacitor or a plurality of small-capacity capacitors which are connected in series.
The capacity of each large-capacity capacitor is 100 uF-400 uF.
The capacity of each small-capacity capacitor is 0.1 uF-1 uF.
In a preferred embodiment of the present invention, the fast electronic switch of the high frequency bi-directional irreversible electroporation pulse system comprises an insulated gate bipolar transistor and an IGBT driving circuit.
In a preferred embodiment of the present invention, the charging switch of the high-frequency bi-directional irreversible electroporation pulse system includes a first charging switch KJ1 and a second charging switch KJ2.
After the first resistor R1 and the fourth resistor R4 are connected in series, one end of the first resistor R1 is arranged between the charging switch KJ1 and the second charging switch KJ2, and the other end of the first resistor R4 is grounded.
A first feedback signal point is arranged between the resistor R1 and the fourth resistor R4, and the first feedback signal is fed back to the upper-layer information management device.
In a preferred embodiment of the present invention, the discharge switch of the high-frequency bi-directional irreversible electroporation pulse system includes a first discharge switch KJ3 and a second discharge switch KJ4.
The first discharge switch KJ3 is connected to one pole of the discharge electrode.
The second discharge switch KJ4 is connected with the other stage of the discharge electrode.
After the second resistor R2 and the third resistor R3 are connected in series, one end of the second resistor R2 is arranged between the fast electronic switch and the first discharging switch KJ3, and the other end of the second resistor R3 is grounded.
And a second feedback signal point is arranged between the second resistor R2 and the third resistor R3, and the second feedback signal is fed back to the upper-layer information management device.
The technical effects are as follows: and controlling the selection of the discharge electrodes and the discharge sequence through the setting of the working parameters.
The embodiment of the invention has the beneficial effects that:
According to the invention, the working parameters are set through the upper information management device, the control signals are generated through the lower computer control device, and the system can accurately control the parameters such as the frequency, the amplitude, the width, the shape and the like of the high-frequency bidirectional irreversible electroporation pulse so as to meet the requirements of different application scenes.
The energy storage control module in the lower computer control device can monitor the residual capacity of the energy storage module in real time, and adjust the duration and the intensity of the electroporation pulse signal according to the change of the capacity, thereby realizing the self-adaptive adjustment of the system and improving the stability and the efficiency of the system.
The pH control module can receive the pH measured value of the tissue to be detected, and adjust the parameters of the electroporation pulse signal according to the measured result so as to ensure that the influence on the biological tissue in the perforation process is minimized and the integrity of the biological tissue is protected.
The invention can carry out photoelectric isolation on the control signal and the feedback signal through the first photoelectric isolation module and the second photoelectric isolation module, improves the safety and the reliability of the system, and prevents the problems of signal interference, circuit short circuit and the like.
The invention can monitor the feedback signal of the bidirectional high-voltage pulse discharge main loop in real time through the voltage and current detection circuit, detect parameters such as charging voltage, discharging current and the like, and upload detection results to the upper information management device, thereby realizing real-time monitoring and feedback of the running state of the system.
The invention can filter the feedback signal through the signal filtering module, effectively reduce noise and interference in the signal, improve the stability and anti-interference capability of the system and ensure the accuracy and reliability of electroporation operation.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of the structure of a high frequency bi-directional irreversible electroporation pulse system of the present invention;
FIG. 2 is a schematic diagram of the overall structure of a high frequency bi-directional irreversible electroporation pulse system according to the invention;
FIG. 3 is a schematic diagram of the connection of the modules of the high frequency bi-directional irreversible electroporation pulse system of the present invention;
FIG. 4 is a schematic diagram of a circuit configuration of a bi-directional high voltage pulse discharge main loop of the high frequency bi-directional irreversible electroporation pulse system of the present invention.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments of the present invention. The components of the embodiments of the present invention generally described and illustrated in the figures herein can be arranged and designed in a wide variety of different configurations.
Referring to fig. 1 to 4, an embodiment of the present invention provides a high-frequency bidirectional irreversible electroporation pulse system, which includes an upper information management device, a lower computer control device and a bidirectional high-voltage pulse discharge main circuit;
the upper information management device sets working parameters of the bidirectional high-voltage pulse discharge main loop and transmits the working parameters to the lower computer control device;
the lower computer control device receives the working parameters set by the upper information management device, generates control signals and transmits the control signals to the bidirectional high-voltage pulse discharge main loop;
the bidirectional high-voltage pulse discharge main loop receives the control signal, generates a high-frequency bidirectional irreversible electroporation pulse signal, and returns a feedback signal to the upper-layer information management device.
As shown in fig. 2, the upper layer information management device includes a parameter setting module, an encoded signal generating module, a feedback signal receiving module and a parameter transmitting module;
The parameter setting module performs data interaction with a user or input equipment, and inputs working parameters, wherein the working parameters comprise at least one of pulse frequency, pulse amplitude, pulse width, pulse shape, pulse interval, pulse lifting time, pulse repetition times and pulse mode;
The coding signal generation module processes, verifies, codes and converts the working parameters to generate coding signals, and the coding signals adjust the working state of the bidirectional high-voltage pulse discharge main loop, wherein the working state comprises starting, stopping, parameter adjusting and the like;
The parameter transmission module (adopting a communication protocol or an interface) transmits the coded signal to the lower computer control device;
The feedback signal receiving module receives the feedback signal returned by the bidirectional high-voltage pulse discharging main loop, analyzes and processes the feedback signal, and transmits the feedback signal to the coding signal generating module to generate a coding signal.
As shown in fig. 2, the lower computer control device comprises a high-frequency bidirectional pulse generation control module, a time sequence function control module, an energy storage control module and a pH control module;
the high-frequency bidirectional pulse generation control module receives the working parameters and the feedback signals, analyzes and processes the working parameters and the feedback signals, and generates the control signals;
Specifically, the high-frequency bidirectional pulse generation control module adopts a field programmable gate array (FPGA or CPLD) as a central controller, and controls charging time and discharging time together with the time sequence function control module, controls connection of electrodes, monitors charging voltage and data acquisition, sets parameters such as the width of discharging pulses and the number of pulses, monitors a discharging process, and controls and monitors data acquisition of discharging voltage and current.
The time sequence function control module controls the starting time of charge and discharge and the duration time of charge and discharge;
the energy storage module receives, stores and releases electric power to provide electric power supply;
the energy storage control module monitors the residual capacity of the energy storage module and adjusts the duration and the intensity of the high-frequency bidirectional irreversible electroporation pulse signal according to the change of the residual capacity;
The pH control module receives a pH measured value of the tissue to be detected, and adjusts the duration and the intensity of the high-frequency bidirectional irreversible electroporation pulse signal according to the pH measured value.
Wherein, energy storage control module includes:
the capacitance sensor is used for collecting capacitance data and monitoring the capacitance in the energy storage module in real time;
the energy storage comparison processing unit compares the current capacitance with a preset capacitance threshold;
The energy storage parameter adjusting unit is used for controlling the output end of the bidirectional high-voltage pulse discharge main loop to stop outputting when the current capacitance is lower than a preset capacitance threshold value, and adjusting the pulse width of the high-frequency bidirectional irreversible electroporation pulse signal based on the current capacitance when the current capacitance is higher than the preset capacitance threshold value;
the capacitance sensor driving unit is used for driving and controlling the capacitance sensor to monitor the capacitance of the energy storage module in real time;
The energy storage signal driving unit drives the high-frequency bidirectional pulse generation control module and the time sequence function control module to realize real-time adjustment of parameters according to the adjustment signals of the energy storage parameter adjustment unit;
And the energy storage integrated MCU unit coordinates functions among the capacitance sensor, the energy storage comparison processing unit, the energy storage parameter adjusting unit, the capacitance sensor driving unit and the energy storage signal driving unit.
Specifically, the energy storage control module effectively controls and manages the energy storage module, and ensures the normal operation and safety of the system. The capacity of the energy storage module is monitored in real time through the capacity sensor, the energy storage condition of the energy storage module is obtained, the output end of the bidirectional high-voltage pulse discharge main loop is controlled to stop outputting or adjust pulse width according to the state of the current capacity, stable output of pulse signals is ensured, the duration and the intensity of high-frequency bidirectional irreversible electroporation pulse signals are adjusted according to the change of the capacity, the requirements of different experiments or applications are met, meanwhile, overload or capacity damage of the energy storage module is prevented through monitoring and adjusting the capacity, and the stability and the reliability of a system are improved.
The technical effects are as follows: the capacitance is managed and controlled by monitoring and adjusting the capacitance in real time, so that overload and damage of an energy storage module are avoided, high-efficiency utilization and storage of energy are ensured, and the energy utilization rate of the system is improved; by controlling and adjusting the output of the pulse signals, the stable working state of the system is maintained, the system faults and instability are reduced, the requirements of different experiments or applications are met, and greater flexibility and adjustability are provided.
Wherein, the pH control module includes:
The pH value acquisition unit drives the pH sensor to acquire pH value data of an electrolysis product close to the electrode;
the pH comparison processing unit is used for comparing the current pH value with a preset pH threshold value;
The pH parameter adjusting unit is used for shortening the pulse duration time, reducing the pulse intensity when the current pH value is within a preset pH range, prolonging the pulse duration time and increasing the pulse intensity when the current pH value is not within the preset pH range;
Specifically, when the current pH value is within a preset pH range, the pulse duration is shortened, the pulse intensity is reduced, and the output end of the bidirectional high-voltage pulse discharge main loop is controlled to stop outputting. When the current pH value is within the preset pH range, the electrolytic product is excessively generated, and the electrolytic capability needs to be weakened, so that the pulse time needs to be reduced, the pulse intensity is reduced, the further generation of the product is reduced, and the excessive generation is avoided.
When the current pH value is not in the preset pH range, the pulse width of the high-frequency bidirectional irreversible electroporation pulse signal is adjusted based on the current pH value, so that the pulse duration is prolonged, and the pulse intensity is increased. When the current pH value is not within the preset pH range, the generation amount of the electrolysis product is insufficient, and the electrolysis capacity needs to be increased, so that the pulse application time needs to be prolonged, the chance of electrolysis generation is increased, or the pulse intensity is increased to enhance the electrolysis effect, and more electrolysis products are promoted to be generated.
The pH sensor driving unit is used for driving and controlling the pH sensor to monitor the pH value of the electrolysis product close to the electrode in real time;
the pH signal driving unit drives the high-frequency bidirectional pulse generation control module and the time sequence function control module to realize real-time adjustment of parameters according to the adjustment signals of the pH parameter adjustment unit;
And the pH integrated MCU unit coordinates functions among the pH value acquisition unit, the pH comparison processing unit, the pH parameter adjustment unit, the pH sensor driving unit, the pH signal driving unit and the pH signal driving unit.
Specifically, a pH value acquisition unit in the pH control module is arranged at a position, close to an electrode, of the bidirectional high-voltage pulse discharge main loop, and acquires the pH value of the surrounding environment of the electrode in real time.
The technical effects are as follows: the system can adapt to different pH conditions more quickly, and ensures the stability and reliability of the high-frequency bidirectional irreversible electroporation pulse system under different pH conditions.
The lower computer control device further comprises a first photoelectric isolation module and a second photoelectric isolation module;
the first photoelectric isolation module performs photoelectric isolation on the control signal;
the second photoelectric isolation module performs photoelectric isolation on the feedback signal.
Wherein each of the photovoltaic isolation modules comprises:
the photoelectric driving circuit receives an input signal and converts the input signal into an input current and/or an input voltage, and the input signal comprises the control signal or the feedback signal;
a light emitting diode for receiving the input current and/or the input voltage and generating an optical signal;
And the phototriode receives the optical signal and converts the optical signal into an output signal.
In particular, the opto-isolator (Optoisolator) is a device having input and output terminals, which internally contains a Light Emitting Diode (LED) and a phototransistor (phototransistor or photodiode). The input signal generates an optical signal through the LED, and the optical signal is received by the phototriode and converted into an output signal, so that electric isolation between the input signal and the output signal is realized, noise down disturbance of an external noise signal to the internal control unit is reduced, and the reliability of the control unit is improved.
The lower computer control device further comprises a power amplifying circuit for amplifying the power of the control signal.
Wherein the power amplification circuit includes:
the control signal input interface is used for receiving the control signal and carrying out impedance matching and protection on the control signal;
the power driving circuit receives the control signal transmitted by the control signal input interface and generates a current and/or voltage signal;
And the power amplifier is used for receiving the current and/or voltage signals generated by the power driving circuit and amplifying the power.
The technical effects are as follows: the control signal from the control signal source is amplified to a sufficient power level by signal amplification and power supply to drive the bi-directional high voltage pulse discharge main loop to generate a high frequency bi-directional irreversible electroporation pulse signal.
The lower computer control device further comprises a voltage and current detection circuit, receives feedback signals of the bidirectional high-voltage pulse discharge main loop, detects charging voltage, discharging voltage and discharging current, and uploads detection results to the upper information management device.
Wherein, the voltage current detection circuit includes:
A voltage-current sensor that converts voltage and/or current signals into measurable electrical signals;
The signal conditioning circuit is used for amplifying, filtering and linearizing the measurable electric signal to obtain an analog voltage and/or current signal;
an ADC analog-to-digital converter that converts the analog voltage and/or current signals to digital voltage and/or current signals;
And the digital processing circuit is used for processing, decoding and checking the digital voltage and/or current signals.
Specifically, the voltage and the current are measured by the sensor, and after signal conditioning and analog-to-digital conversion, the detection result is provided to the digital processing circuit in a digital form. The digital processing circuit can further process the detection result and upload the result to the upper information management device for monitoring and analysis.
The technical effects are as follows: through the voltage and current detection circuit, the system can monitor and control the voltage and current parameters of the high-frequency bidirectional irreversible electroporation pulse in real time.
The lower computer control device further comprises a signal filtering module, and the feedback signal is filtered.
Wherein, the signal filtering module includes:
An operational amplifier amplifying the feedback signal;
And a capacitor for performing frequency selection for amplifying the feedback signal.
The technical effects are as follows: by selecting proper filter types and parameters, the signal filtering module can realize the filtering function of the feedback signal, remove noise and unnecessary frequency components and extract the needed effective information.
As shown in fig. 4, the bidirectional high-voltage pulse discharge main circuit includes a charging power supply U1, an energy storage capacitor set, a fast electronic switch and a discharge electrode;
a charging switch is arranged between the charging power supply U1 and the energy storage capacitor group;
The energy storage capacitor group is connected with the discharge electrode through the fast electronic switch;
and a discharge switch is arranged between the fast electronic switch and the discharge electrode.
Wherein, as shown in fig. 4, the energy storage capacitor group comprises a large-capacity capacitor group and a small-capacity capacitor group which are connected in parallel;
The high-capacity capacitor group comprises a high-capacity capacitor or a plurality of high-capacity capacitors which are connected in series;
The small-capacity capacitor comprises a small-capacity capacitor or a plurality of small-capacity capacitors which are connected in series;
the capacity of each large-capacity capacitor is 100 uF-400 uF;
the capacity of each small-capacity capacitor is 0.1 uF-1 uF.
Specifically, the large-capacity capacitor group comprises a first capacitor C1, a third capacitor C3 and a fifth capacitor C5;
The small-capacity capacitor group includes a second capacitor C2, a fourth capacitor C4, and a sixth capacitor C6.
Wherein, as shown in fig. 4, the fast electronic switch comprises an insulated gate bipolar transistor and an IGBT driving circuit.
Specifically, the fast electronic switch includes a first fast electronic switch K1, a second fast electronic switch K2, a third fast electronic switch K3, and a fourth fast electronic switch K4.
Wherein, as shown in fig. 4, the charging switch comprises a first charging switch KJ1 and a second charging switch KJ2;
after the first resistor R1 and the fourth resistor R4 are connected in series, one end of the first resistor R1 is arranged between the charging switch KJ1 and the second charging switch KJ2, and the other end of the first resistor R4 is grounded;
A first feedback signal point is arranged between the resistor R1 and the fourth resistor R4, and the first feedback signal is fed back to the upper-layer information management device.
Wherein, as shown in fig. 4, the discharge switch comprises a first discharge switch KJ3 and a second discharge switch KJ4;
the first discharge switch KJ3 is connected with one pole of the discharge electrode;
The second discharge switch KJ4 is connected with the other stage of the discharge electrode;
After the second resistor R2 and the third resistor R3 are connected in series, one end of the second resistor R2 is arranged between the fast electronic switch and the first discharging switch KJ3, and the other end of the second resistor R3 is grounded;
and a second feedback signal point is arranged between the second resistor R2 and the third resistor R3, and the second feedback signal is fed back to the upper-layer information management device.
The technical effects are as follows: and controlling the selection of the discharge electrodes and the discharge sequence through the setting of the working parameters.
When the energy storage capacitor is in operation, the discharge electrode is inserted into a focus part, and the first charging switch KJ1 and the second charging switch KJ2 are closed to charge the energy storage capacitor group. When the voltage of the focus part reaches a preset value, the first charging switch KJ1 and the second charging switch KJ2 are opened, the first discharging switch KJ3 and the second discharging switch KJ4 are closed, the energy storage capacitor group is discharged, the fast electronic switch forms high-frequency high-voltage pulse under the action of the IGBT driving circuit, and the pulse width can be set to be in a form that pulses with the same pulse width between 250 nanoseconds and 5 mu s are conducted alternately between the two electrodes. The electrodes are subjected to bidirectional pulse discharge, and on the setting of a treatment area, high-voltage steep pulses form a reticular discharge area in tissues, so that an effective irreversible electric field covers tumor tissues as much as possible, ablation blind areas are reduced, and the effectiveness of a treatment plan is enhanced; at the rising edge of the pulse, a perforation of the cells is achieved, the process of perforation being irreversible, whereby cell inactivation is achieved.
The invention adopts a capacitor group charging and discharging mode, takes a Field Programmable Gate Array (FPGA) as a central controller, takes an insulated gate bipolar transistor (IGBD) as a steep pulse generation switch, can generate bipolar high-voltage pulse with the frequency up to 250kHZ, has the output voltage of 1000v-5000v, and can regulate positive and negative pulses within the range of 2 [ mu ] s-50 [ mu ] s. The method comprises the steps of selecting the number of probes to be used and probe combinations through a user operation interface, and setting parameters such as voltage (1000 v-5000 v), positive pulse width (2 [ mu ] s-50 [ mu ] s), negative pulse width (2 [ mu ] s-50 [ mu ] s), pulse number in groups (1-15), group number (1-250 groups) and the like through electrode spacing.
The high-frequency bidirectional irreversible electroporation pulse system uses the bidirectional high-voltage pulse with nanosecond rising edge to perform nanometer-order electric shock perforation on the outer membrane of the biological cells, so as to realize the inactivation effect on the biological cells. The high-frequency bidirectional irreversible electroporation pulse system can be applied to tumor treatment, not only can realize the inactivation treatment of tumor cells, but also can realize the effects of minimally invasive and non-thermal deposition. In addition, because irreversible electroporation can only perforate general tissue cells, does not act on connective tissue cells such as blood vessels and nerves, and meanwhile, the high-frequency bidirectional irreversible electroporation realizes tumor ablation operation under the conditions of local anesthesia, no injection of muscle relaxant and no mechanical ventilation of a breathing machine, so that the safety and quality of the operation can be fundamentally improved. Compared with the traditional unipolar irreversible electroporation pulse sequence, the method can better and more uniformly increase the induced transmembrane potential of the closely arranged cells to the simulated electroporation threshold value, so that the ablation area is more uniform. The invention can achieve the purposes of good tumor ablation effect and tumor growth inhibition, and has good safety and effectiveness.
The high-frequency bidirectional irreversible electroporation pulse system has the following advantages when in practical application: before the treatment is carried out on the patient, the patient only needs to be subjected to local anesthesia; the tumor ablation area of the patient can be more uniform; bipolar pulse parameters can be accurately set; based on a high-speed digital signal microprocessor, high-speed real-time acquisition of high-voltage pulse feedback signals is realized, real-time monitoring of high-voltage pulse discharge in the whole treatment process is realized, and the requirement on real-time performance in the system working process is met; the bipolar pulse discharge of a plurality of electrodes is adopted, and on the setting of a treatment area, a reticular discharge area is formed in the tissue by the high-voltage steep pulse, so that an effective irreversible electric field covers the tumor tissue as much as possible, ablation blind areas are reduced, and the effectiveness of a treatment plan is enhanced; the output pulse form of the invention is a pulse with the same pulse width between 2us and 50us, and the pulse is conducted alternately between two electrodes; the invention has good software and hardware protection mechanism, and ensures the safety of the whole operation treatment.
It is to be understood that the above-described embodiments of the present invention are merely illustrative of or explanation of the principles of the present invention and are in no way limiting of the invention. Accordingly, any modification, equivalent replacement, improvement, etc. made without departing from the spirit and scope of the present invention should be included in the scope of the present invention. Furthermore, the appended claims are intended to cover all such changes and modifications that fall within the scope and boundary of the appended claims, or equivalents of such scope and boundary.
Claims (18)
1. The high-frequency bidirectional irreversible electroporation pulse system is characterized by comprising an upper-layer information management device, a lower computer control device and a bidirectional high-voltage pulse discharge main loop;
the upper information management device sets working parameters of the bidirectional high-voltage pulse discharge main loop and transmits the working parameters to the lower computer control device;
the lower computer control device receives the working parameters set by the upper information management device, generates control signals and transmits the control signals to the bidirectional high-voltage pulse discharge main loop;
The bidirectional high-voltage pulse discharge main loop receives the control signal, generates a high-frequency bidirectional irreversible electroporation pulse signal, and returns a feedback signal to the upper-layer information management device;
the lower computer control device comprises a high-frequency bidirectional pulse generation control module, a time sequence function control module, an energy storage control module and a pH control module;
the pH control module receives a pH measured value of the tissue to be detected, and adjusts the duration and the intensity of the high-frequency bidirectional irreversible electroporation pulse signal according to the pH measured value;
the pH control module comprises a pH value acquisition unit, a pH comparison processing unit, a pH sensor driving unit, a pH signal driving unit and a pH integrated MCU unit;
the pH parameter adjusting unit is used for shortening the pulse duration time, reducing the pulse intensity when the current pH value is within a preset pH range, prolonging the pulse duration time and increasing the pulse intensity when the current pH value is not within the preset pH range.
2. The high-frequency bi-directional irreversible electroporation pulse system of claim 1, wherein the upper information management device comprises a parameter setting module, a coded signal generation module, a feedback signal reception module, and a parameter transmission module;
The parameter setting module performs data interaction with a user or input equipment, and inputs working parameters, wherein the working parameters comprise at least one of pulse frequency, pulse amplitude, pulse width, pulse shape, pulse interval, pulse lifting time, pulse repetition times and pulse mode;
The coding signal generation module processes, verifies, codes and converts the working parameters to generate coding signals, and the coding signals adjust the working state of the bidirectional high-voltage pulse discharge main loop;
the parameter transmission module transmits the coding signal to the lower computer control device;
The feedback signal receiving module receives the feedback signal returned by the bidirectional high-voltage pulse discharging main loop, analyzes and processes the feedback signal, and transmits the feedback signal to the coding signal generating module to generate a coding signal.
3. The high-frequency bi-directional irreversible electroporation pulse system of claim 1, wherein in the lower computer control apparatus,
The high-frequency bidirectional pulse generation control module receives the working parameters and the feedback signals, analyzes and processes the working parameters and the feedback signals, and generates the control signals;
the time sequence function control module controls the starting time of charge and discharge and the duration time of charge and discharge;
the energy storage module receives, stores and releases electric power to provide electric power supply;
The energy storage control module monitors the residual capacity of the energy storage module, and adjusts the duration and the intensity of the high-frequency bidirectional irreversible electroporation pulse signal according to the change of the residual capacity.
4. A high frequency bi-directional irreversible electroporation pulse system of claim 3, wherein the energy storage control module comprises:
the capacitance sensor is used for collecting capacitance data and monitoring the capacitance in the energy storage module in real time;
the energy storage comparison processing unit compares the current capacitance with a preset capacitance threshold;
The energy storage parameter adjusting unit is used for controlling the output end of the bidirectional high-voltage pulse discharge main loop to stop outputting when the current capacitance is lower than a preset capacitance threshold value, and adjusting the pulse width of the high-frequency bidirectional irreversible electroporation pulse signal based on the current capacitance when the current capacitance is higher than the preset capacitance threshold value;
the capacitance sensor driving unit is used for driving and controlling the capacitance sensor to monitor the capacitance of the energy storage module in real time;
The energy storage signal driving unit drives the high-frequency bidirectional pulse generation control module and the time sequence function control module to realize real-time adjustment of parameters according to the adjustment signals of the energy storage parameter adjustment unit;
And the energy storage integrated MCU unit coordinates functions among the capacitance sensor, the energy storage comparison processing unit, the energy storage parameter adjusting unit, the capacitance sensor driving unit and the energy storage signal driving unit.
5. The high frequency bi-directional irreversible electroporation pulse system of claim 3, wherein in the pH control module,
The pH value acquisition unit drives the pH sensor to acquire pH value data of an electrolysis product close to the electrode;
The pH comparison processing unit compares the current pH value with a preset pH threshold value;
The pH sensor driving unit drives and controls the pH sensor to monitor the pH value of an electrolysis product close to the electrode in real time;
The pH signal driving unit drives the high-frequency bidirectional pulse generation control module and the time sequence function control module to realize real-time adjustment of parameters according to the adjustment signals of the pH parameter adjustment unit;
The pH integrated MCU unit coordinates functions among the pH value acquisition unit, the pH comparison processing unit, the pH parameter adjustment unit, the pH sensor driving unit, the pH signal driving unit and the pH signal driving unit.
6. The high frequency bi-directional irreversible electroporation pulse system of claim 3, wherein the lower computer control apparatus further comprises a first opto-electrical isolation module and a second opto-electrical isolation module;
the first photoelectric isolation module performs photoelectric isolation on the control signal;
the second photoelectric isolation module performs photoelectric isolation on the feedback signal.
7. The high frequency bi-directional irreversible electroporation pulse system of claim 6, wherein each of the opto-electronic isolation modules comprises:
the photoelectric driving circuit receives an input signal and converts the input signal into an input current and/or an input voltage, and the input signal comprises the control signal or the feedback signal;
a light emitting diode for receiving the input current and/or the input voltage and generating an optical signal;
And the phototriode receives the optical signal and converts the optical signal into an output signal.
8. A high frequency bi-directional irreversible electroporation pulse system as in claim 3, wherein the lower computer control further comprises a power amplification circuit for power amplifying the control signal.
9. The high frequency bi-directional irreversible electroporation pulse system of claim 8, wherein the power amplification circuitry comprises:
the control signal input interface is used for receiving the control signal and carrying out impedance matching and protection on the control signal;
the power driving circuit receives the control signal transmitted by the control signal input interface and generates a current and/or voltage signal;
And the power amplifier is used for receiving the current and/or voltage signals generated by the power driving circuit and amplifying the power.
10. The high-frequency bi-directional irreversible electroporation pulse system of claim 3, wherein the lower computer control device further comprises a voltage and current detection circuit for receiving a feedback signal of the bi-directional high-voltage pulse discharge main loop, detecting a charge voltage, a discharge voltage and a discharge current, and uploading the detection result to the upper information management device.
11. The high frequency bi-directional irreversible electroporation pulse system of claim 10, wherein the voltage current detection circuitry comprises:
A voltage-current sensor that converts voltage and/or current signals into measurable electrical signals;
The signal conditioning circuit is used for amplifying, filtering and linearizing the measurable electric signal to obtain an analog voltage and/or current signal;
an ADC analog-to-digital converter that converts the analog voltage and/or current signals to digital voltage and/or current signals;
And the digital processing circuit is used for processing, decoding and checking the digital voltage and/or current signals.
12. A high frequency bi-directional irreversible electroporation pulse system as in claim 3, wherein the lower computer control further comprises a signal filtering module for filtering the feedback signal.
13. The frequency bi-directional irreversible electroporation pulse system of claim 12, wherein the signal filtering module comprises:
An operational amplifier amplifying the feedback signal;
And a capacitor for performing frequency selection for amplifying the feedback signal.
14. The high-frequency bi-directional irreversible electroporation pulse system of claim 1, wherein the bi-directional high voltage pulse discharge main loop comprises a charging power supply U1, an energy storage capacitor bank, a fast electronic switch, and a discharge electrode;
a charging switch is arranged between the charging power supply U1 and the energy storage capacitor group;
The energy storage capacitor group is connected with the discharge electrode through the fast electronic switch;
and a discharge switch is arranged between the fast electronic switch and the discharge electrode.
15. The high frequency bi-directional irreversible electroporation pulse system of claim 14, wherein the storage capacitor bank comprises a high capacity capacitor bank and a low capacity capacitor bank connected in parallel;
The high-capacity capacitor group comprises a high-capacity capacitor or a plurality of high-capacity capacitors which are connected in series;
The small-capacity capacitor comprises a small-capacity capacitor or a plurality of small-capacity capacitors which are connected in series;
the capacity of each large-capacity capacitor is 100 uF-400 uF;
the capacity of each small-capacity capacitor is 0.1 uF-1 uF.
16. The high frequency bi-directional irreversible electroporation pulse system of claim 14, wherein the fast electronic switch comprises an insulated gate bipolar transistor and an IGBT drive circuit.
17. The high frequency bi-directional irreversible electroporation pulse system of claim 14, wherein the charge switch comprises a first charge switch KJ1 and a second charge switch KJ2;
after the first resistor R1 and the fourth resistor R4 are connected in series, one end of the first resistor R1 is arranged between the charging switch KJ1 and the second charging switch KJ2, and the other end of the first resistor R4 is grounded;
A first feedback signal point is arranged between the resistor R1 and the fourth resistor R4, and the first feedback signal is fed back to the upper-layer information management device.
18. The high frequency bi-directional irreversible electroporation pulse system of claim 14, wherein the discharge switch comprises a first discharge switch KJ3 and a second discharge switch KJ4;
the first discharge switch KJ3 is connected with one pole of the discharge electrode;
The second discharge switch KJ4 is connected with the other stage of the discharge electrode;
After the second resistor R2 and the third resistor R3 are connected in series, one end of the second resistor R2 is arranged between the fast electronic switch and the first discharging switch KJ3, and the other end of the second resistor R3 is grounded;
and a second feedback signal point is arranged between the second resistor R2 and the third resistor R3, and the second feedback signal is fed back to the upper-layer information management device.
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