CN112451086A - Direct current bias type pulse-based targeted cell ablation system - Google Patents

Direct current bias type pulse-based targeted cell ablation system Download PDF

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Publication number
CN112451086A
CN112451086A CN202011433465.8A CN202011433465A CN112451086A CN 112451086 A CN112451086 A CN 112451086A CN 202011433465 A CN202011433465 A CN 202011433465A CN 112451086 A CN112451086 A CN 112451086A
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China
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electric field
direct current
pulse
bias type
generating device
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吕彦鹏
程显
李景丽
程子霞
葛国伟
张鹤
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Zhengzhou University
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Zhengzhou University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206—Generators therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00577—Ablation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00613—Irreversible electroporation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206—Generators therefor
    • A61B2018/1266—Generators therefor with DC current output

Abstract

Embodiments of the present disclosure disclose targeted cell ablation systems based on direct current biased pulses. One embodiment of the system comprises: a direct current electric field generating device, a high voltage pulse electric field generating device, a direct current bias type pulse generating device and an applying device, wherein: the direct current electric field generating device is used for generating a direct current electric field and sending the direct current electric field to the direct current bias type pulse generating device; the high-voltage pulse electric field generating device is used for generating a high-voltage pulse electric field; the direct current bias type pulse generating device is used for combining the direct current electric field and the high-voltage pulse electric field to generate direct current bias type pulses; the applying device is used for receiving the direct current bias type pulse sent by the direct current bias type pulse generating device and applying the direct current bias type pulse to a preset target tissue for cell ablation. The embodiment realizes effective removal of cells in target region tissues remained after the action of the traditional pulse electric field, thereby improving the efficiency of cell ablation.

Description

Direct current bias type pulse-based targeted cell ablation system
Technical Field
The embodiment of the disclosure relates to the technical field of medical treatment, in particular to a targeted cell ablation system based on direct-current bias type pulse.
Background
The irreversible electroporation effect caused by the pulse electric field has gradually become a research hotspot of the bioelectromagnetic. The irreversible electroporation effect refers to the phenomenon that under the action of a pulse electric field with high enough strength, micropores on a cell membrane cannot be closed automatically, the structural integrity of the cell membrane is damaged, various particles continuously enter and exit the cell through the micropores, stable unbalance is caused in the cell, and the death of the cell is induced.
However, when ablating tissue cells using conventional pulsed electric fields, there are often problems:
firstly, due to the non-uniform characteristics of the electrical parameters of the biological tissue, the distribution of the pulse electric field in a partial area is distorted, so that cells can only generate reversible electroporation, and a residual focal zone appears in situ in target area tissues, thereby reducing the ablation efficiency;
second, due to the inherent electric field distribution characteristics of the needle electrodes when delivering pulses, a wide range of reversible electroporation zones in the tissue can be created. This area is unavoidable, thereby preventing further enlargement of the intended tissue ablation area, which in turn results in a gradual decrease in ablation efficiency with increasing intended tissue size.
Disclosure of Invention
This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.
Some embodiments of the present disclosure propose targeted cell ablation systems based on dc-biased pulses to address one or more of the technical problems mentioned in the background section above.
In a first aspect, some embodiments of the present disclosure provide a dc bias pulse-based targeted cell ablation system, where the dc bias pulse-based targeted cell ablation system includes: a direct current electric field generating device, a high voltage pulse electric field generating device, a direct current bias type pulse generating device and an applying device, wherein: the dc electric field generating device is connected to the dc offset pulse generating device, and the dc electric field generating device is configured to generate a dc electric field and send the dc electric field to the dc offset pulse generating device; the high-voltage pulse electric field generating device is connected with the direct-current bias type pulse generating device, wherein the high-voltage pulse electric field generating device is used for generating a high-voltage pulse electric field and sending the high-voltage pulse electric field to the direct-current bias type pulse generating device; the dc bias type pulse generating device is connected to the applying device, and the dc bias type pulse generating device is configured to receive the dc electric field and the high voltage pulse electric field, and combine the dc electric field and the high voltage pulse electric field to generate a dc bias type pulse; the applying device is used for receiving the direct current bias type pulse sent by the direct current bias type pulse generating device and applying the direct current bias type pulse to a preset target tissue for cell ablation.
In some embodiments, the above-mentioned application device comprises: parameter setting means and pulse transmission device, wherein: the parameter setting device is connected with the direct current bias type pulse generating device and used for receiving the direct current bias type pulse sent by the direct current bias type pulse generating device and carrying out parameter setting on the direct current bias type pulse based on the preset target tissue so as to generate direct current bias type pulse parameters.
In some embodiments, the pulse transmitting device is configured to receive the dc bias type pulse parameters transmitted by the parameter setting device, and apply the dc bias type pulse to a preset target tissue based on the dc bias type pulse parameters.
In some embodiments, the dc electric field generated by the dc electric field generating device is between 1 minute and 1 hour during the interval of the pulsed electric field generated by the high voltage pulsed electric field generating device and after the subsequent combined action with the pulsed electric field.
In some embodiments, the voltage range of the high-voltage pulsed electric field generated by the high-voltage pulsed electric field generating device is between 0 and 5 kV.
In some embodiments, the high-voltage pulse electric field generated by the high-voltage pulse electric field generating device has a width ranging from 500ns to 1 ms.
In some embodiments, the frequency range of the high-voltage pulsed electric field generated by the high-voltage pulsed electric field generating device is between 0.1Hz and 100 kHz.
In some embodiments, the number of the high-voltage pulsed electric fields generated by the high-voltage pulsed electric field generating device ranges from 1 to 300.
In some embodiments, the voltage range of the dc electric field generated by the dc electric field generating device is between 5V and 50V.
In a second aspect, some embodiments of the present disclosure provide an electronic device, comprising: one or more processors; a storage device having one or more programs stored thereon, which when executed by one or more processors, cause the one or more processors to implement the method described in any of the implementations of the first aspect.
In a third aspect, some embodiments of the present disclosure provide a computer readable medium on which a computer program is stored, wherein the program, when executed by a processor, implements the method described in any of the implementations of the first aspect.
The above embodiments of the present disclosure have the following advantages: first, a direct current electric field may be generated by a direct current electric field generating device. Therefore, the strong electrolysis effect is generated by applying direct current, so that the preset tissue cells subjected to reversible electroporation after the pulsed electric field treatment can be effectively eliminated. Secondly, a high-voltage pulse electric field can be generated by a high-voltage pulse electric field generating device. This provides a necessary condition for the subsequent generation of the dc bias type pulse. Then, the dc bias type pulse generator may combine the dc electric field and the high voltage pulse electric field to generate a dc bias type pulse. Thereby enabling subsequent application of the predetermined tissue to provide support. Finally, the above-mentioned dc bias type pulse may be applied to a predetermined tissue by an applying device to perform ablation. And because the direct current is added into the direct current bias type pulse, the electrolysis effect generated by the direct current can effectively remove the residual tissue cells, and the ablation efficiency is improved. Therefore, the problem that due to the uneven characteristic of the electrical parameters of the biological tissue, the distribution of the pulse electric field in partial areas is distorted, so that reversible electroporation can only be carried out on cells, and a residual focal zone appears in situ in target area tissues, thereby reducing the ablation efficiency is solved. On the other hand, the inherent electric field distribution characteristic of needle electrodes in pulse delivery results in the generation of a relatively large, unavoidable reversible electroporation zone in the tissue. However, when the direct current bias type pulse is adopted, the reversible electroporation cells in the area can be ablated through the electrolysis effect of the direct current bias type pulse, so that the ablation efficiency is further improved. Thereby solving the two technical problems mentioned in the background art. Furthermore, if the frequency of application of the pulsed electric field in cell ablation is in the range of 0.1-10Hz, therefore, simply applying a DC bias electric field during the pulsed electric field interval does not significantly increase the treatment time.
Drawings
The above and other features, advantages and aspects of various embodiments of the present disclosure will become more apparent by referring to the following detailed description when taken in conjunction with the accompanying drawings. Throughout the drawings, the same or similar reference numbers refer to the same or similar elements. It should be understood that the drawings are schematic and that elements and elements are not necessarily drawn to scale.
Fig. 1 is a schematic diagram of an application scenario of a dc bias pulse based targeted cell ablation system according to some embodiments of the present disclosure;
FIG. 2 is a schematic structural diagram of one embodiment of a DC-biased pulse-based targeted cell ablation system according to the present disclosure;
FIG. 3 is a schematic structural diagram of another embodiment of a DC-biased pulse-based targeted cell ablation system according to the present disclosure;
fig. 4 is a schematic diagram of output waveforms of some embodiments of a dc-biased pulse-based targeted cell ablation system according to the present disclosure;
fig. 5 is an experimental schematic of an output waveform of some embodiments of a dc-biased pulse-based targeted cell ablation system according to the present disclosure;
fig. 6 is a graph of tissue H & E staining results for some embodiments of a dc-biased pulse-based targeted cell ablation system according to the present disclosure;
FIG. 7 is a schematic structural diagram of an electronic device suitable for use in implementing some embodiments of the present disclosure.
Detailed Description
Embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. While certain embodiments of the present disclosure are shown in the drawings, it is to be understood that the disclosure may be embodied in various forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided for a more thorough and complete understanding of the present disclosure. It should be understood that the drawings and embodiments of the disclosure are for illustration purposes only and are not intended to limit the scope of the disclosure.
It should be noted that, for convenience of description, only the portions related to the related invention are shown in the drawings. The embodiments and features of the embodiments in the present disclosure may be combined with each other without conflict.
It should be noted that the terms "first", "second", and the like in the present disclosure are only used for distinguishing different devices, modules or units, and are not used for limiting the order or interdependence relationship of the functions performed by the devices, modules or units.
It is noted that references to "a", "an", and "the" modifications in this disclosure are intended to be illustrative rather than limiting, and that those skilled in the art will recognize that "one or more" may be used unless the context clearly dictates otherwise.
The names of messages or information exchanged between devices in the embodiments of the present disclosure are for illustrative purposes only, and are not intended to limit the scope of the messages or information.
The present disclosure will be described in detail below with reference to the accompanying drawings in conjunction with embodiments.
Fig. 1 illustrates an application scenario diagram 100 of a dc bias pulse based targeted cell ablation system according to some embodiments of the present disclosure.
As shown in fig. 1, an application scenario of the dc bias pulse-based targeted cell ablation system according to some embodiments of the present disclosure may be used with an oscilloscope 101 and an electrode needle 102. The present disclosure provides a dc-biased pulse generating device 103 for outputting a dc-biased pulse to ablate cells in a predetermined tissue.
In some embodiments, the present disclosure may set the pitch of the electrode needles 102 to 5 mm. And is coupled to the output end of the dc offset type pulse generating device 103 through the current probe and the voltage probe of the oscilloscope 101, so as to convert the electrical signals detected by the current probe and the voltage probe into waveform curves to be displayed on the display screen of the oscilloscope 101, for an operator to monitor the pulse parameters. And the electrode can be connected to the dc bias type pulse output terminal of the dc bias type pulse generating device 103 to receive the dc bias type pulse signal output from the dc bias type pulse generating device 103 and monitor the effect of the output pulse on the cell according to the dc bias type pulse signal.
With continued reference to fig. 2, a schematic structural diagram of one embodiment of the dc bias pulse-based targeted cell ablation system of the present disclosure is shown. As shown in fig. 2, the dc bias pulse-based targeted cell ablation system of the present embodiment may include: a direct current electric field generating device 1, a high voltage pulse electric field generating device 2, a direct current bias type pulse generating device 3 and an applying device 4.
In some embodiments, the dc electric field generating device 1 is connected to the dc bias type pulse generating device 2. The dc electric field generator 1 may be any of various devices (for example, a dry cell battery, a storage battery, a solar cell, a dc generator, etc.) capable of generating a dc electric field. Here, the direct-current electric field generating apparatus 1 may be configured to generate a direct current and transmit the direct current to the direct-current bias type pulse generating apparatus 3.
In some embodiments, the high-voltage pulse electric field generating device 2 is connected to the dc bias type pulse generating device 3. The high-voltage pulse electric field generator 2 may be any of various devices capable of generating a high-voltage pulse electric field (e.g., a high-voltage pulse generator based on a Marx circuit, a pulse forming line, a linear transformer drive source, etc.). Here, the high-voltage pulse electric field generating device 2 may be configured to generate a high-voltage pulse electric field and transmit the high-voltage pulse electric field to the dc bias type pulse generating device 3.
In some embodiments, the dc bias type pulse generating device 3 is connected to the applying device 4. The dc bias type pulse generating device 3 may be any of various devices capable of combining the dc power and the high-voltage pulse electric field. Here, the dc bias type pulse generating device 3 may be configured to receive the dc electric field and the high voltage pulse electric field, and to generate a dc bias type pulse by combining the dc electric field and the high voltage pulse electric field.
In some embodiments, the applying device 4 may be various devices for applying pulses (e.g., electrodes, concentric needle electrodes, bi-needle electrodes, single-needle electrodes, multi-lead needle electrodes, etc.). Here, the applying device 4 may be configured to receive the dc bias type pulse transmitted by the dc bias type pulse generating device, and apply the dc bias type pulse to a preset target tissue for ablation.
The above embodiments of the present disclosure have the following advantages: first, a direct current electric field may be generated by a direct current electric field generating device. Therefore, the strong electrolysis effect is generated by applying direct current, so that the preset tissue cells subjected to reversible electroporation after the pulsed electric field treatment can be effectively eliminated. Secondly, a high-voltage pulse electric field can be generated by a high-voltage pulse electric field generating device. This provides a necessary condition for the subsequent generation of the dc bias type pulse. Then, the dc bias type pulse generator may combine the dc electric field and the high voltage pulse electric field to generate a dc bias type pulse. Thereby enabling subsequent application of the predetermined tissue to provide support. Finally, the above-mentioned dc bias type pulse may be applied to a predetermined tissue by an applying device to perform ablation. And because the direct current is added into the direct current bias type pulse, the electrolysis effect generated by the direct current can effectively remove the residual tissue cells, and the ablation efficiency is improved. Therefore, the problem that due to the uneven characteristic of the electrical parameters of the biological tissue, the distribution of the pulse electric field in partial areas is distorted, so that reversible electroporation can only be carried out on cells, and a residual focal zone appears in situ in target area tissues, thereby reducing the ablation efficiency is solved. On the other hand, the inherent electric field distribution characteristic of needle electrodes in pulse delivery results in the generation of a relatively large, unavoidable reversible electroporation zone in the tissue. However, when the direct current bias type pulse is adopted, the reversible electroporation cells in the area can be ablated through the electrolysis effect of the direct current bias type pulse, so that the ablation efficiency is further improved. And solves two technical problems mentioned in the background art. Furthermore, if the frequency of application of the pulsed electric field in cell ablation is in the range of 0.1-10Hz, therefore, simply applying a DC bias electric field during the pulsed electric field interval does not significantly increase the treatment time.
With continued reference to fig. 3, a schematic structural diagram of another embodiment of the dc bias pulse-based targeted cell ablation system of the present disclosure is shown. Like the dc bias type pulse-based targeted cell ablation system in the embodiment of fig. 2, the dc bias type pulse-based targeted cell ablation system in the embodiment may also include a dc electric field generating device 1, a high-voltage pulsed electric field generating device 2, a dc bias type pulse generating device 3 and an applying device 4. For a specific structural relationship, reference may be made to the related description in the embodiment of fig. 2, which is not described herein again.
Unlike the targeted cell ablation system based on dc bias type pulses in the embodiment of fig. 2, the application device in this embodiment includes: a parameter setting device 5 and a pulse transmitting device 6, wherein the parameter setting device can be various devices for setting parameters. The parameter setting device 5 may support parameter adjustment of the dc offset type pulse. The pulse transmitter 6 may be any of various devices for transmitting pulses (e.g., a plate electrode, a concentric needle electrode, a double-needle electrode, a single-needle electrode, a multi-lead needle electrode, etc.). The parameter setting device 5 is connected to the dc offset type pulse generating device, and configured to receive the dc offset type pulse sent by the dc offset type pulse generating device, and perform parameter setting on the dc offset type pulse based on the preset target tissue to generate a dc offset type pulse parameter. The pulse transmitting device is used for receiving the direct current bias type pulse parameters transmitted by the parameter setting device and applying the direct current bias type pulse to a preset target tissue based on the direct current bias type pulse parameters.
Unlike the targeted cell ablation system based on dc bias type pulse in the embodiment of fig. 2, the dc electric field generated by the dc electric field generating device 1 in this embodiment has a duration of 1 minute to 1 hour during the interval of the pulsed electric field generated by the high voltage pulsed electric field generating device and after the subsequent combined action with the pulsed electric field.
Unlike the targeted cell ablation system based on the dc bias type pulse in the embodiment of fig. 2, the voltage range of the high-voltage pulsed electric field generated by the high-voltage pulsed electric field generating device 2 in this embodiment is between 0 and 5 kV.
Unlike the targeted cell ablation system based on the dc bias type pulse in the embodiment of fig. 2, the width of the high-voltage pulsed electric field generated by the high-voltage pulsed electric field generating device 2 in this embodiment ranges from 500ns to 1 ms.
Unlike the targeted cell ablation system based on the dc bias type pulse in the embodiment of fig. 2, the frequency range of the high-voltage pulsed electric field generated by the high-voltage pulsed electric field generating device 2 in this embodiment is between 0.1Hz and 100 kHz.
Unlike the targeted cell ablation system based on dc bias type pulse in the embodiment of fig. 2, the number of the high-voltage pulsed electric fields generated by the high-voltage pulsed electric field generating device 2 in this embodiment ranges from 1 to 300.
Unlike the targeted cell ablation system based on the dc bias type pulse in the embodiment of fig. 2, the voltage range of the dc electric field generated by the dc electric field generating device 1 in this embodiment is between 5V and 50V.
The dc-biased pulse generator 3 and the related contents serve as an inventive point of the present disclosure, thereby solving the technical problem mentioned in the background art that "a reversible electroporation region with a large range is generated in the tissue due to the inherent electric field distribution characteristic when the needle electrode is used to transmit the pulse". This area is unavoidable, thereby preventing further enlargement of the intended tissue ablation area, resulting in a gradual decrease in ablation efficiency with increasing intended tissue size ". The factors that lead to the gradual decrease in ablation efficiency with increasing preset tissue size tend to be as follows: the inherent electric field distribution characteristics of conventional pulses result in a relatively large range of reversible electroporation zones in the desired tissue. This area is more difficult to avoid, thus preventing further enlargement of the intended tissue ablation area. If the above-mentioned factors are solved, the ablation region of the preset tissue can be further enlarged, thereby increasing the ablation efficiency. In order to achieve the above advantageous effects, the present disclosure introduces a direct current bias type pulse generating device 3. Here, the dc bias type pulse generating device 3 is introduced for generating a dc bias type pulse by a high voltage pulse electric field and a dc electric field. The reversible electroporation region generated by the pulse component when the needle electrode transmits the generated DC bias type pulse electric field is converted into the ablation region through the DC component in the DC bias type pulse. Therefore, the ablation area of the preset tissue can be effectively enlarged, and the ablation efficiency is effectively improved.
The above embodiments of the present disclosure have the following advantages: first, a direct current electric field may be generated by a direct current electric field generating device. Therefore, the strong electrolysis effect is generated by applying direct current, so that the preset tissue cells subjected to reversible electroporation after the pulsed electric field treatment can be effectively eliminated. Secondly, a high-voltage pulse electric field can be generated by a high-voltage pulse electric field generating device. This provides a necessary condition for the subsequent generation of the dc bias type pulse. Then, the dc bias type pulse generator may combine the dc electric field and the high voltage pulse electric field to generate a dc bias type pulse. Thereby enabling subsequent application of the predetermined tissue to provide support. Finally, the above-mentioned dc bias type pulse may be applied to a predetermined tissue by an applying device to perform ablation. And because the direct current is added into the direct current bias type pulse, the electrolysis effect generated by the direct current can effectively remove the residual tissue cells, and the ablation efficiency is improved. Therefore, the problem that due to the uneven characteristic of the electrical parameters of the biological tissue, the distribution of the pulse electric field in partial areas is distorted, so that reversible electroporation can only be carried out on cells, and a residual focal zone appears in situ in target area tissues, thereby reducing the ablation efficiency is solved. On the other hand, the inherent electric field distribution characteristic of needle electrodes in pulse delivery results in the generation of a relatively large, unavoidable reversible electroporation zone in the tissue. However, when the direct current bias type pulse is adopted, the reversible electroporation cells in the area can be ablated through the electrolysis effect of the direct current bias type pulse, so that the ablation efficiency is further improved. Thereby solving the two technical problems mentioned in the background art. Furthermore, if the frequency of application of the pulsed electric field in cell ablation is in the range of 0.1-10Hz, therefore, simply applying a DC bias electric field during the pulsed electric field interval does not significantly increase the treatment time.
With continued reference to fig. 4, shown is an output waveform schematic of some embodiments of a dc-biased pulse-based targeted cell ablation system according to the present disclosure.
In some embodiments, the width of the high voltage pulsed electric field may be in the order of nanoseconds or microseconds or milliseconds. The width of the high voltage pulsed electric field may be in the range of 500ns to 1 ms. The frequency of the high voltage pulsed electric field may be in the range of 0.1Hz to 100 kHz. The voltage of the high voltage pulsed electric field may be in the range of 0 to 5 kV. Correspondingly, the voltage of the dc electric field may be in the range of 5V to 50V. The action time of the direct current electric field can be in the range of 1 minute to 1 hour.
With continued reference to fig. 5, an experimental schematic of the output waveform of some embodiments of a dc-biased pulse-based targeted cell ablation system according to the present disclosure is shown.
The experimental procedure was as follows:
firstly, the liver tissue of white rabbit in New Zealand is taken as an experimental object to research the ablation effect of the direct current bias type pulse electric field on the biological tissue. 3 New Zealand white rabbits (female, 6 months old, body weight 2.5 kg. + -. 0.2kg) were prepared. The experiment strictly executes relevant regulations in the experimental animal management regulations of the people's republic of China. The output voltage and current of the direct current bias type pulse can be collected by an oscilloscope. The electrode used in the experiment was a stainless steel double needle electrode. The electrode needle center spacing is 5 mm. The diameter is 1 mm. The exposed length was 8 mm.
In the second step, before the liver tissue was pulsed, anesthesia was first performed by injection of 3% sodium pentobarbital solution through the rabbit ear vein (1 mL/kg). The anesthesia duration is more than 1 hour, and sufficient time is provided for the experimental operation. During the experiment, the rabbits were fixed on the operating table in a lying position, and the new zealand white rabbits were subjected to surgical laparotomy. The electrode needles adopt spacers to fix the distance, and the distance between the centers of the electrode needles can be 5 mm. Pulse electric fields with different parameters are respectively applied through electrode needles, after pulse treatment is finished, a medical suture line is adopted to suture the abdominal wound of the rabbit, and the sutured New Zealand white rabbit is placed in a sterile animal laboratory to be raised for 3 days.
And thirdly, feeding the new zealand white rabbits in an animal laboratory for 3 days, euthanizing the experimental rabbits, opening the abdomen and taking out liver tissues. And taking a picture of the ablation region of the fresh liver tissue by adopting a preset camera, and counting the ablation region by adopting preset software. Each set of parameters was repeated three times and statistical difference analysis was performed using a one-way variance method. After sampling, the samples were soaked in 10% formalin solution for 72 hours. Then embedding the cells into paraffin for fixation, cutting the paraffin to prepare tissue sections, and observing whether the morphological structure of the cells is complete or not through H & E staining.
Experimental results As can be seen in FIG. 5, when a high-voltage pulse electric field is applied alone, the ablation area of the predetermined tissue may be 39mm2. When applied separatelyIn the case of a DC electric field, the ablation area of the preset tissue can be 40mm2. While the preset tissue ablation area may be 77mm when applying a DC bias type pulse2. It is known that the application of the dc bias type pulse has an effect of increasing the ablation area compared to the application of the high voltage pulse alone or the application of the dc electric field alone.
With continued reference to fig. 6, a graph of tissue H & E staining results for some embodiments of a dc-biased pulse-based targeted cell ablation system according to the present disclosure is shown.
Referring to the above experimental examples, after the H & E staining scan of the liver tissue, the boundary between the liver tissue ablation region and the normal tissue can be observed more clearly and accurately. Take the DC bias type pulse (high voltage pulse electric field parameters 50, 1500V, 0.5Hz, 10 mus pulse and DC electric field parameters 1 minute, 25V pulse) as an example. The actual liver tissue is composed of liver lobules, blood vessels and bile ducts, and the structural heterogeneity thereof causes the difference of electrical parameters thereof. The actual electric field distribution is not a standard dumbbell or ellipse. As can be seen from fig. 6, the ablation boundary is very clear and no residual cells are present.
The above description is only a preferred embodiment of the application and is illustrative of the principles of the technology employed. It will be appreciated by those skilled in the art that the scope of the invention herein disclosed is not limited to the particular combination of features described above, but also encompasses other arrangements formed by any combination of the above features or their equivalents without departing from the spirit of the invention. For example, the above features may be replaced with (but not limited to) features having similar functions disclosed in the present application.
Referring now to FIG. 7, a block diagram of an electronic device (e.g., computing device 101 of FIG. 1)700 suitable for use in implementing some embodiments of the present disclosure is shown. The electronic device shown in fig. 7 is only an example, and should not bring any limitation to the functions and the scope of use of the embodiments of the present disclosure.
As shown in fig. 7, electronic device 700 may include a processing means (e.g., central processing unit, graphics processor, etc.) 701 that may perform various appropriate actions and processes in accordance with a program stored in a Read Only Memory (ROM)702 or a program loaded from storage 708 into a Random Access Memory (RAM) 703. In the RAM703, various programs and data necessary for the operation of the electronic apparatus 700 are also stored. The processing device 701, the ROM702, and the RAM703 are connected to each other by a bus 704. An input/output (I/O) interface 706 is also connected to bus 704.
Generally, the following devices may be connected to the I/O interface 705: input devices 706 including, for example, a touch screen, touch pad, keyboard, mouse, camera, microphone, accelerometer, gyroscope, etc.; an output device 707 including, for example, a Liquid Crystal Display (LCD), a speaker, a vibrator, and the like; storage 708 including, for example, magnetic tape, hard disk, etc.; and a communication device 709. The communication means 709 may allow the electronic device 700 to communicate wirelessly or by wire with other devices to exchange data. While fig. 7 illustrates an electronic device 700 having various means, it is to be understood that not all illustrated means are required to be implemented or provided. More or fewer devices may alternatively be implemented or provided. Each block shown in fig. 7 may represent one device or may represent multiple devices as desired.
In particular, according to some embodiments of the present disclosure, the processes described above with reference to the flow diagrams may be implemented as computer software programs. For example, some embodiments of the present disclosure include a computer program product comprising a computer program embodied on a computer readable medium, the computer program comprising program code for performing the method illustrated in the flow chart. In some such embodiments, the computer program may be downloaded and installed from a network via communications means 709, or may be installed from storage 708, or may be installed from ROM 702. The computer program, when executed by the processing device 701, performs the above-described functions defined in the methods of some embodiments of the present disclosure.
It should be noted that the computer readable medium described above in some embodiments of the present disclosure may be a computer readable signal medium or a computer readable storage medium or any combination of the two. A computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any combination of the foregoing. More specific examples of the computer readable storage medium may include, but are not limited to: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a Random Access Memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In some embodiments of the disclosure, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device. In some embodiments of the present disclosure, however, a computer readable signal medium may include a propagated data signal with computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated data signal may take many forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof. A computer readable signal medium may also be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device. Program code embodied on a computer readable medium may be transmitted using any appropriate medium, including but not limited to: electrical wires, optical cables, RF (radio frequency), etc., or any suitable combination of the foregoing.
In some embodiments, the clients, servers may communicate using any currently known or future developed network Protocol, such as HTTP (HyperText Transfer Protocol), and may interconnect with any form or medium of digital data communication (e.g., a communications network). Examples of communication networks include a local area network ("LAN"), a wide area network ("WAN"), the Internet (e.g., the Internet), and peer-to-peer networks (e.g., ad hoc peer-to-peer networks), as well as any currently known or future developed network.
Computer program code for carrying out operations for embodiments of the present disclosure may be written in any combination of one or more programming languages, including an object oriented programming language such as Java, Smalltalk, C + +, and conventional procedural programming languages, such as the "C" programming language or similar programming languages. The program code may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the case of a remote computer, the remote computer may be connected to the user's computer through any type of network, including a Local Area Network (LAN) or a Wide Area Network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet service provider).
The flowchart and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present disclosure. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems which perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.
The foregoing description is only exemplary of the preferred embodiments of the disclosure and is illustrative of the principles of the technology employed. It will be appreciated by those skilled in the art that the scope of the invention in the embodiments of the present disclosure is not limited to the specific combination of the above-mentioned features, but also encompasses other embodiments in which any combination of the above-mentioned features or their equivalents is made without departing from the inventive concept as defined above. For example, the above features and (but not limited to) technical features with similar functions disclosed in the embodiments of the present disclosure are mutually replaced to form the technical solution.

Claims (10)

1. A DC-biased pulse-based targeted cell ablation system, wherein the DC-biased pulse-based targeted cell ablation system comprises: a direct current electric field generating device, a high voltage pulse electric field generating device, a direct current bias type pulse generating device and an applying device, wherein:
the direct current electric field generating device is connected with the direct current bias type pulse generating device, wherein the direct current electric field generating device is used for generating a direct current electric field and sending the direct current electric field to the direct current bias type pulse generating device;
the high-voltage pulse electric field generating device is connected with the direct-current bias type pulse generating device, and is used for generating a high-voltage pulse electric field and sending the high-voltage pulse electric field to the direct-current bias type pulse generating device;
the direct current bias type pulse generating device is connected with the applying device, and is used for receiving the direct current electric field and the high-voltage pulse electric field and combining the direct current electric field and the high-voltage pulse electric field to generate a direct current bias type pulse;
the applying device is used for receiving the direct current bias type pulse sent by the direct current bias type pulse generating device and applying the direct current bias type pulse to a preset target tissue for cell ablation.
2. The dc-biased pulse-based targeted cell ablation system of claim 1, wherein the application device comprises: parameter setting means and pulse transmission device, wherein:
the parameter setting device is connected with the direct current bias type pulse generating device and used for receiving the direct current bias type pulse sent by the direct current bias type pulse generating device and carrying out parameter setting on the direct current bias type pulse based on the preset target tissue so as to generate direct current bias type pulse parameters;
the pulse sending device is used for receiving the direct current bias type pulse parameters sent by the parameter setting device and applying the direct current bias type pulse to a preset target tissue based on the direct current bias type pulse parameters.
3. The targeted cell ablation system based on DC bias type pulse according to claim 2, wherein the DC electric field generated by the DC electric field generating device lasts for 1 minute to 1 hour in the interval time of the pulse electric field generated by the high voltage pulse electric field generating device and after the subsequent combined action with the pulse electric field.
4. The direct current bias type pulse-based targeted cell ablation system according to claim 3, wherein the voltage range of the high voltage pulsed electric field generated by the high voltage pulsed electric field generating device is between 0 and 5 kV.
5. The direct current bias type pulse-based targeted cell ablation system according to claim 4, wherein the width of the high voltage pulsed electric field generated by the high voltage pulsed electric field generating device ranges from 500ns to 1 ms.
6. The targeted cell ablation system based on direct current bias type pulse of claim 5, wherein the frequency range of the high voltage pulse electric field generated by the high voltage pulse electric field generating device is between 0.1Hz and 100 kHz.
7. The direct current bias type pulse-based targeted cell ablation system of claim 6, wherein the number of the high voltage pulsed electric fields generated by the high voltage pulsed electric field generating device ranges from 1 to 300.
8. The targeted cell ablation system based on direct current bias type pulse according to claim 7, wherein the voltage range of the direct current electric field generated by the direct current electric field generating device is between 5V and 50V.
9. An electronic device, comprising:
one or more processors;
a storage device having one or more programs stored thereon;
when executed by the one or more processors, cause the one or more processors to implement the method of any one of claims 1-8.
10. A computer-readable medium, on which a computer program is stored, wherein the program, when executed by a processor, implements the method of any one of claims 1-8.
CN202011433465.8A 2020-12-09 2020-12-09 Direct current bias type pulse-based targeted cell ablation system Pending CN112451086A (en)

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