Electrosurgical apparatus, systems, and pulse control methods

Abstract

The application provides an electric ablation device, system and pulse control method. The ablation device comprises an ablation device for extending into target biological tissue, and a pulse generator and a direct current generator electrically connected with the ablation device, wherein the ablation device comprises a first electrode and a second electrode; the pulse generator is used for delivering an electric pulse signal to the ablation device to generate nanoscale holes in the target biological tissue; the electric pulse signal at least comprises a first pulse sequence, and the first pulse sequence comprises at least one first pulse; and the direct current generator is used for delivering a direct current signal to the ablation device to differentiate the acid-base property of the region near the first electrode and the second electrode. Under the electric perforation effect, the application can generate nanoscale holes from cells, the cytoplasm flowing out of the nanoscale holes can be used as an electrolyte environment when the direct current signal is delivered, the conductivity can be improved, the ablation area can be increased, and the ablation time can be shortened.

Description

Technical Field

[0001] This application relates to the field of medical device technology, and more specifically, to an electroablation device, system, and pulse control method. Background Technology

[0002] Pulsed electric field ablation (also known as electroporation ablation) and electrolytic ablation are two commonly used physical ablation techniques for tumors.

[0003] Pulsed electric field ablation creates nanoscale electroporation pores in cell membranes by releasing high-voltage, short-duration electric field pulses, leading to efflux of intracellular substances or apoptosis. Electroporation includes reversible and irreversible electroporation. Pulsed electric field ablation can precisely destroy target tissues (such as myocardial cells or tumor cells) while minimizing damage to surrounding normal tissues. However, the ablation range of a single pulsed electric field ablation is limited, the electric field energy attenuates significantly in non-tissue contact areas, the electric field coverage is greatly reduced in areas with complex anatomical structures, and multiple electrodes are required for large tumors, resulting in a significant burden on patients during treatment.

[0004] Electrolytic ablation involves delivering low-voltage direct current to the treatment area through one or more electrodes inserted into the tissue. This causes a change in the local pH level, creating a cytotoxic environment, and the formation of toxic chemicals during electrolysis, leading to cell death. Electrolytic ablation is suitable for destroying large tissue volumes (such as solid tumors), but the treatment time is long, potentially lasting several hours, which can be quite burdensome for patients. Summary of the Invention

[0005] This application addresses the shortcomings of existing methods by proposing an electroablation device, system, and pulse control method to solve the technical problems in related technologies where tumor cell ablation either has a small ablation area or a long ablation time.

[0006] In a first aspect, embodiments of this application provide an electroablation device, comprising: An ablation device for inserting into target biological tissue, comprising at least one first electrode and at least one second electrode; A pulse generator, electrically connected to the ablation device, is used to deliver an electrical pulse signal to the ablation device, the electrical pulse signal being used to induce nanoscale pores in the target biological tissue; the electrical pulse signal includes at least a first pulse sequence, the first pulse sequence including at least one first pulse. A DC generator, electrically connected to the ablation device, is used to supply a DC signal to the ablation device, making the area near the first electrode strongly acidic and the area near the second electrode strongly alkaline; the electrical pulse signal and the DC signal form an ablation signal sequence.

[0007] Optionally, when the pulse generator applies an electrical pulse signal to the first electrode and / or the second electrode, an electroporation ablation region is formed in the target biological tissue. The electroporation ablation region includes an irreversible electroporation ablation region and a reversible electroporation ablation region from the inside out. At least one first electrode is disposed in the irreversible electroporation ablation region, and at least one second electrode is disposed in the electroporation ablation region; When the DC generator applies a DC signal to the first electrode and the second electrode, an acid-base ablation region gradually forms within the target biological tissue, covering the electroporation ablation region.

[0008] Optionally, the electrical pulse signal further includes a second pulse sequence, the second pulse sequence including at least one second pulse, the amplitude of the first pulse being greater than that of the second pulse, and the width of the first pulse being less than that of the second pulse; Within one signal cycle of the ablation sequence signal, the first pulse, the second pulse, and the DC signal are arranged sequentially; or, within one signal cycle of the ablation sequence signal, the first pulse, the DC signal, and the second pulse are arranged sequentially.

[0009] Optionally, the ablation sequence signal is a signal cycle, including at least a set of first pulses with opposite polarities and a continuous DC signal; Alternatively, the ablation sequence signal may include multiple signal cycles, one of which includes at least one set of first pulses of opposite polarity and the DC signal within a predetermined time period.

[0010] Optionally, the ablation sequence signal is a signal cycle, including at least one set of first pulses with opposite polarity, at least one set of second pulses with opposite polarity, and a continuous DC signal; Alternatively, the ablation sequence signal may include multiple combined pulse sequences and a continuous DC signal, wherein the combined pulse sequences include a set of first pulses of opposite polarity and a set of second pulses of opposite polarity; Alternatively, the ablation sequence signal may include multiple signal cycles, one of which includes at least one set of first pulses of opposite polarity, at least one set of second pulses of opposite polarity, and the DC signal within a predetermined time period.

[0011] Optionally, in one of the signal cycles of the ablation sequence signal, a set of second pulses of opposite polarity is arranged before the DC signal within a predetermined time period; or A second set of pulses with opposite polarity is arranged after the DC signal within a predetermined time period.

[0012] Optionally, there is a zero-level interval between two first pulses of opposite polarity in the same group, between two second pulses of opposite polarity in the same group, between the first pulse and the DC signal, and between the second pulse and the DC signal.

[0013] Optionally, the ablation sequence signal includes a first pulse sequence, a second pulse sequence, and a direct current signal; The ablation sequence signal includes multiple signal cycles, one of which includes a unipolar first pulse, a unipolar second pulse, and a DC signal within a predetermined time period. There is no zero-level interval between the first pulse, the second pulse, and the DC signal, and there is a zero-level interval between two adjacent ablation sequence signals.

[0014] Optionally, the electroablation device further includes at least one of the following: The first pulse is a nanosecond pulse, and the second pulse is a microsecond pulse; The first pulse and the second pulse are square wave pulses; The pulse width of the first pulse is 0.5 nanoseconds to 1000 nanoseconds, and the pulse amplitude is ±1 kV to 20 kV. The pulse width of the second pulse is 1 microsecond to 1000 microseconds, and the pulse amplitude is ±0 volts to 5 kilovolts; The DC signal has a voltage of 0V-300V and a current of 0mA-250mA.

[0015] Secondly, embodiments of this application provide an electroablation system, including the electroablation device described in the above embodiments and a host computer; The host computer is communicatively connected to the pulse generator and DC generator in the electroablation device.

[0016] Thirdly, embodiments of this application provide a pulse control method for the electroablation device using the above embodiments, comprising: Electrical pulse signals and DC signals are delivered to the ablation device.

[0017] The beneficial technical effects of the technical solutions provided in this application include: In this embodiment, the ablation device includes a first electrode as the anode and a second electrode as the cathode. A pulse generator for transmitting electrical pulse signals and a DC generator for transmitting DC signals are electrically connected to the ablation device. The high voltage of the electrical pulse signals is transmitted to the ablation device, causing nanoscale pores to form within the cells of the target biological tissue. Cytoplasm flows out through these nanoscale pores, acting as the electrolyte environment for the DC signal transmission. This improves the diffusion efficiency of electrolytic products in the DC signal and increases the electrolyte concentration within the target biological tissue. When the first electrode acts as the anode and the second electrode as the cathode, anions in the electrolyte environment rapidly move towards the first electrode, and cations rapidly move towards the second electrode. The first electrode releases electrons and undergoes an oxidation reaction, while the second electrode absorbs electrons and undergoes a reduction reaction. This causes the pH value near the first electrode to rapidly become strongly acidic, and the pH value near the second electrode to rapidly become strongly alkaline. Ultimately, the acid-base differentiation between the two electrodes forms a toxic environment harmful to tumor cells, promoting cell inactivation within the reversible electroporation ablation area of ​​the target biological tissue, thereby further accelerating tumor ablation.

[0018] This application combines electroporation ablation and electrolytic ablation to create an ablation device with, from the inside out, an irreversible electroporation ablation region, a reversible electroporation ablation region, and an acid-base ablation region. The nanoscale pores generated by electroporation ablation promote cytoplasmic outflow, which enhances the diffusion efficiency of electrolytic products in the direct current signal and accelerates the formation of a cytotoxic environment near the first and second electrodes. This cytotoxic environment (acid-base ablation region) further promotes cell inactivation in the reversible electroporation ablation region, accelerating apoptosis in the target tissue. The two ablation methods work synergistically, expanding the ablation range and shortening the treatment time with fewer electrodes, thus reducing tumor recurrence and postoperative complications. Furthermore, the reduced number of electrodes also lessens the burden on the patient.

[0019] Additional aspects and advantages of this application will be set forth in part in the description which follows, and will become apparent from the description or may be learned by practice of this application. Attached Figure Description

[0020] The above and / or additional aspects and advantages of this application will become apparent and readily understood from the following description of the embodiments taken in conjunction with the accompanying drawings, wherein: Figure 1 This is a schematic diagram of the structure of an electroablation device provided in an embodiment of this application; Figure 2 for Figure 1 Top view of the ablation area at point A; Figures 3-5This is a schematic diagram of the pulse waveforms generated in Examples 1 to 3 of the first embodiment of the electroablation device of this application; Figures 6-9 This is a schematic diagram of the pulse waveforms generated in Examples 1 to 4 of the second embodiment of an electroablation device according to this application; Figures 10-11 This is a schematic diagram of the pulse waveforms generated in Examples 1 and 2 of the third embodiment of an electroablation device according to this application; Figure 12 This is a schematic diagram of an electroablation system provided in an embodiment of this application.

[0021] Explanation of reference numerals in the attached figures: 10-Ablation device; 11-First electrode; 12-Second electrode; 20 - Pulse generator; 30 - DC generator; 41 - Irreversible electroporation ablation zone; 42 - Reversible electroporation ablation zone; 43 - Acid-base ablation zone; 50 - First pulse sequence; 51 - First pulse; 60 - Second pulse sequence; 61 - Second pulse; 70 - Combined pulse sequence; 80 - DC signal; 90 - Host computer; S1 - Signal period. Detailed Implementation

[0022] The embodiments of this application are described below with reference to the accompanying drawings. It should be understood that the embodiments described below with reference to the accompanying drawings are exemplary descriptions for explaining the technical solutions of the embodiments of this application, and do not constitute a limitation on the technical solutions of the embodiments of this application.

[0023] Those skilled in the art will understand that, unless specifically stated otherwise, the terms "described" and "the" as used herein may also include plural forms. It should be further understood that the term "comprising" as used in the specification of this application means the presence of the stated features, integers, steps, operations, elements, and / or components, but does not exclude other features, information, data, steps, operations, elements, components, and / or combinations thereof supported by the art. The term "and / or" as used herein refers to at least one of the items defined by the term; for example, "A and / or B" can be implemented as "A," or as "B," or as "A and B."

[0024] To make the objectives, technical solutions, and advantages of this application clearer, the embodiments of this application will be described in further detail below with reference to the accompanying drawings.

[0025] Among related technologies, pulsed electric field ablation (electroporation ablation) can rapidly induce apoptosis, but the ablation area in a single session is limited, requiring multiple electrodes for large tumors, resulting in a significant burden on patients during treatment. Electrolytic ablation delivers low-voltage direct current to the treatment area through one or more electrodes, causing a change in the local pH value and creating a cytotoxic environment. During electrolysis, toxic chemicals are formed, leading to cell death. Electrolytic ablation has the advantage of a larger treatment area, but its treatment time is longer, and the burden on patients is also greater.

[0026] Therefore, there is currently no tumor cell ablation technique that can produce a large ablation area, accelerate the ablation speed, shorten the ablation time, and reduce the burden on patients.

[0027] Reference Figures 1-11 This application provides an electroablation device to solve the above-mentioned technical problems.

[0028] Reference Figures 1-2 An electroablation device includes an ablation device 10 for inserting into a target biological tissue, and a pulse generator 20 and a DC generator 30 electrically connected to the ablation device 10.

[0029] Reference Figures 1-2 The ablation device 10 includes at least one first electrode 11 and at least one second electrode 12.

[0030] The pulse generator 20 is used to deliver an electrical pulse signal to the ablation device 10, the electrical pulse signal being used to create nanoscale pores in the target biological tissue. The electrical pulse signal includes at least a first pulse sequence 50, the first pulse sequence 50 including at least one first pulse 51.

[0031] The DC generator 30 is used to supply a DC signal 80 to the ablation device 10, causing the regions near the first electrode 11 and the second electrode 12 to differentiate into acidic and alkaline states. The electrical pulse signal and the DC signal 80 together form an ablation signal sequence.

[0032] During the acid-base differentiation process near the first electrode 11 and the second electrode 12, one electrode acts as the anode and the other as the cathode. In this application, the first electrode 11 is used as the anode and the second electrode 12 as the cathode as an example. During the acid-base differentiation process, anions move towards the first electrode 11, and cations move towards the second electrode 12. The first electrode 11 releases electrons and undergoes an oxidation reaction, while the second electrode 12 absorbs electrons and undergoes a reduction reaction. This causes the region near the first electrode 11 to rapidly become strongly acidic, and the region near the second electrode 12 to rapidly become strongly alkaline. Ultimately, the acid-base differentiation at both electrodes creates a toxic environment harmful to tumor cells.

[0033] In this embodiment, the ablation device 10 includes a first electrode 11 as the anode and a second electrode 12 as the cathode. A pulse generator 20 for transmitting electrical pulse signals and a DC generator 30 for transmitting DC signals 80 are electrically connected to the ablation device 10. The high voltage of the electrical pulse signal (relative to the DC signal) is transmitted to the ablation device 10, causing nanoscale pores to form in the cells of the target biological tissue. Cytoplasm flows out through these nanoscale pores, becoming the electrolyte environment for the DC signal 80. This improves the diffusion efficiency of electrolytic products in the DC signal 80 and increases the electrolyte concentration in the target biological tissue. When the first electrode acts as the anode and the second electrode as the cathode, anions in the electrolyte environment rapidly move towards the first electrode 11, ultimately causing acid-base differentiation at both electrodes to form a toxic environment harmful to tumor cells. This promotes cell inactivation within the reversible electroporation ablation region 42 of the target biological tissue, thereby accelerating tumor cell ablation.

[0034] Optionally, refer to Figures 1-2 When the pulse generator 20 applies an electrical pulse signal to the first electrode 11 and / or the second electrode 12, an electroporation ablation region is formed within the target biological tissue. The electroporation ablation region includes an irreversible electroporation ablation region 41 and a reversible electroporation ablation region 42, extending from the inside out. When the DC generator 30 applies a DC signal to the first electrode 11 and the second electrode 12, an acid-base ablation region 43 gradually forms within the target biological tissue, encapsulating the electroporation ablation region.

[0035] This application combines electroporation ablation and electrolytic ablation to create an irreversible electroporation ablation region 41, a reversible electroporation ablation region 42, and an acid-base ablation region 43 around the ablation device 10 from the inside out. Specifically, the acid-base ablation region 43 formed by the DC signal 80 surrounds the reversible electroporation ablation region 42 and the irreversible electroporation region 41 formed by the electrical pulse signal. The nanoscale pores generated by electroporation ablation promote cytoplasmic outflow. The outflowing cytoplasm increases the diffusion efficiency of electrolytic products in the DC signal 80, increases the electrolyte concentration in the target biological tissue, and accelerates the formation of a cytotoxic environment near the first electrode 11 and the second electrode 12. The formed cytotoxic environment (i.e., the acid-base ablation region 43) further promotes cell inactivation in the reversible electroporation ablation region 42, accelerating apoptosis in the target biological tissue. The two ablation methods work together to complement each other, expanding the ablation range and shortening the ablation time with fewer electrodes. This is especially suitable for solid tumors with unclear boundaries or lesions adjacent to sensitive structures, which can reduce the tumor recurrence rate and the probability of postoperative complications. Moreover, using fewer electrodes can also reduce the physical burden on patients.

[0036] Optionally, refer to Figures 1-2At least one first electrode 11 is disposed in the irreversible electroporation ablation region 41, and at least one second electrode 12 is disposed in the electroporation ablation region.

[0037] In this application, the first electrode 11 and the second electrode 12 can be either electrode needles or electrode conduits, and this application does not impose any specific restrictions.

[0038] Optionally, the first electrode 11 can be a bipolar needle or a bipolar conduit, or it can be a monopolar needle or a monopolar conduit.

[0039] When the first electrode 11 is a bipolar needle or bipolar conduit, i.e., when the first electrode 11 has two or more electrodes, the pulse generator 20 can be connected only to the first electrode 11. In this case, an electroporation ablation region can be formed. The first electrode 11 is arranged in the irreversible electroporation ablation region 41, and the second electrode 12 is arranged in the electroporation ablation region. Specifically, the second electrode 12 can be arranged in the irreversible electroporation ablation region 41, the reversible electroporation ablation region 42, or a region further outward from the reversible electroporation ablation region. The DC generator is connected to one electrode of the first electrode 11 and the second electrode 12.

[0040] When the first electrode 11 is a monopolar needle or a monopolar catheter, meaning there is only one electrode on the first electrode 11, the pulse generator 20 needs to be connected to both the first and second electrodes 11 to form an electroporation ablation area. During ablation treatment, the second electrode 12 can only be inserted into the irreversible electroporation ablation area 41, not the reversible electroporation ablation area 42. In this case, the middle part of the electric field distribution will be concave inward to form a waist, preventing ablation of areas outside the waist. This application combines electroporation ablation and electrolytic ablation to form an acid-base ablation area 43 that covers both the reversible and irreversible electroporation ablation areas 42 and 41. This can promote cell inactivation in the reversible electroporation ablation area 42, accelerate apoptosis of the target biological tissue, improve ablation efficiency and effect, and shorten ablation time.

[0041] Optionally, the first electrode 11 and the second electrode 12 are arranged in a group. In one option, each group of electrodes includes one first electrode 11 and one second electrode 12. In another option, each group of electrodes includes one first electrode 11 and multiple second electrodes 12, thereby achieving wrap-around ablation, which can expand the ablation range and improve the thoroughness of ablation.

[0042] Optionally, the DC generator 30 may output the DC signal 80 before the pulse generator 20 outputs the electrical pulse signal; or the DC signal 80 may output the DC signal 80 after the pulse generator 20 outputs the electrical pulse signal; or the DC signal 80 and the electrical pulse signal may be output simultaneously; or the output times of the DC signal 80 and the electrical pulse signal may at least partially overlap.

[0043] Optionally, the electrical pulse signal may further include a second pulse sequence 60, which includes at least one second pulse 61, wherein the amplitude of the first pulse 51 is greater than that of the second pulse 61, and the width of the first pulse 51 is less than that of the second pulse 61.

[0044] This application achieves ablation by synergistically combining a high-amplitude first pulse 51 with a low-amplitude second pulse 61 to generate a sufficiently strong electric field. This prevents the repair of perforations on the cell membrane surface of cells within the target biological tissue, disrupting the intracellular homeostasis and ultimately leading to cell death. Furthermore, the short duration of both the first and second pulses allows the heat generated during ablation to be rapidly diffused and absorbed by the local tissue. Therefore, the ablation process is independent of thermal effects and does not cause irreversible thermal damage to the tissue, facilitating effective ablation of tumor tissue. Additionally, the second pulse 61 is a low-voltage, wide pulse, while the first pulse 51 is a high-voltage, narrow pulse. During ablation, the synergistic effect of the high-amplitude first pulse 51 and the low-amplitude second pulse 61 expands the perforation range of the cell membrane, further enhancing the ablation effect.

[0045] Reference Figures 6-8 , Figures 10-11 Within one signal period S1 of the ablation sequence signal, the first pulse 51, the second pulse 61, and the DC signal 80 are arranged sequentially.

[0046] Or, refer to Figure 9 Within one signal period S1 of the ablation sequence signal, the first pulse 51, the DC signal 80, and the second pulse 61 are arranged sequentially.

[0047] Optionally, in this embodiment of the application, the first pulse 51 includes a nanosecond pulse, and the second pulse 61 includes a microsecond pulse.

[0048] In this application, the terms "nanosecond pulse," "microsecond pulse," and "millisecond pulse" refer to the order of magnitude of the voltage duration of the pulse, i.e., the order of magnitude of the pulse width. "Nanosecond pulse" means a pulse with a pulse width on the order of nanometers, "microsecond pulse" means a pulse with a pulse width on the order of micrometers, and "millisecond pulse" means a pulse with a pulse width on the order of millimeters.

[0049] Nanosecond pulsed currents act on organelles and cell membranes within a certain range of tissue cells, causing both irreversible and reversible electroporation. Microsecond pulsed currents act on cell membranes within a certain range of tissue cells, causing both irreversible and reversible electroporation. Pre-treating tissue cells with nanosecond pulses within a certain range reduces tissue impedance, providing a more uniform electric field distribution for subsequent microsecond pulses. Afterward, the prolonged electric field from the microsecond pulses creates irreversible electroporation in the cell membrane, leading to the outflow of cell contents, osmotic pressure imbalance, cell necrosis, and promoting cell ablation.

[0050] Optionally, in the first embodiment, the ablation sequence signal includes a first pulse sequence 50 and a DC signal 80, but does not include a second pulse sequence 60. Within one signal period S1 of the ablation sequence signal, the first pulse 51 and the DC signal 80 are arranged sequentially at intervals.

[0051] Reference Figure 3 Example Scheme 1 of this embodiment is: the ablation sequence signal is a signal period S1, including at least a set of first pulses 51 with opposite polarities and a continuous DC signal 80.

[0052] In this electric field application scheme, bidirectional nanosecond pulses are first used to uniformly disrupt cell membranes and organelles, avoiding the charge accumulation effect caused by unipolar pulses. Then, a direct current signal of 80 is continuously applied until the treatment ends. The nano-scale pores pretreated by the nanosecond pulses allow acidic / basic substances to penetrate into the cells, accelerating mitochondrial destruction and cell death; the cytoplasm flowing out through the nano-scale pores acts as an electrolyte, accelerating ion migration and shortening the ablation time; and it also allows for wider diffusion of toxic substances from the direct current, increasing the ablation volume.

[0053] Optionally, in another embodiment, the ablation sequence signal includes multiple signal periods S1, one of which includes at least a set of first pulses 51 with opposite polarities and a DC signal 80 within a predetermined time period.

[0054] Reference Figure 4 Example Scheme 2 of this embodiment is as follows: In one signal period S1 of the ablation sequence signal, a set of nanosecond pulses with opposite polarities are applied, and then a DC signal 80 for a predetermined time is applied.

[0055] Reference Figure 5 Example scheme three of this embodiment is: apply multiple sets of nanosecond pulses with opposite polarities, and then apply a DC signal 80 for a predetermined time.

[0056] This approach combines nanosecond pulses of opposite polarity with a direct current signal 80 in a cyclical manner. In each cycle, the nanosecond pulse opens a new channel, and the direct current further inactivates cells through chemical toxicity. The cyclic superposition expands the ablation range, which can give full play to the synergistic effect of the two energies and achieve significant improvements in ablation efficiency, treatment thoroughness and safety.

[0057] Optionally, in the second embodiment, the ablation sequence signal includes a first pulse sequence 50, a second pulse sequence 60, and a DC signal 80.

[0058] Reference Figure 6 Example Scheme 1 of this embodiment is: the ablation sequence signal is a signal period S1, which includes at least a first pulse 51 with opposite polarity, at least a second pulse 61 with opposite polarity, and a continuous DC signal 80.

[0059] In this electric field application scheme, multiple sets of nanosecond pulses with opposite polarities can be applied first, followed by multiple sets of microsecond pulses with opposite polarities, and finally a continuous DC signal 80 is applied until the treatment ends.

[0060] This method, through the combination of the first pulse 51 and the second pulse 61, can increase the cell ablation range. By applying a continuous direct current signal 80, it can accelerate toxin diffusion and promote cell apoptosis.

[0061] Reference Figure 7 Example Scheme 2 of this embodiment is: the ablation sequence signal is a signal period S1, which includes multiple combined pulse sequences 70 and a continuous DC signal 80. The combined pulse sequence 70 includes a first pulse 51 with opposite polarity and a second pulse 61 with opposite polarity.

[0062] In this scheme, a set of nanosecond pulses with opposite polarities and a set of microsecond pulses with opposite polarities can be applied first, as a combined pulse sequence 70. Then, multiple combined pulse sequences 70 are applied in a loop, and finally a DC signal 80 is applied continuously until the treatment ends.

[0063] This approach weakens tissue repair capabilities layer by layer through cyclic nanosecond and microsecond pulses, while direct current electrolysis completely inactivates regenerating cells, effectively reducing the recurrence rate. Furthermore, the combined pulses can penetrate high-impedance areas (such as fibrotic tissue), and direct current electrolysis covers low-impedance areas (such as highly vascularized tumors), making it suitable for heterogeneous lesions.

[0064] Therefore, this combined application scheme can achieve significant improvements in ablation efficiency, range expansion, and tissue selectivity through multi-stage energy synergy.

[0065] The ablation sequence signal may also include multiple signal periods S1, one of which includes at least one set of first pulses 51 with opposite polarities, at least one set of second pulses 61 with opposite polarities, and a DC signal 80 within a predetermined time period.

[0066] In this protocol, within one signal cycle S1 of the ablation sequence signal, a set of nanosecond pulses of opposite polarity and a set of microsecond pulses of opposite polarity can be applied first, followed by a DC signal 80 for a predetermined duration. This cycle is repeated multiple times until the treatment is complete. Alternatively, multiple sets of nanosecond pulses of opposite polarity can be applied first, followed by one or more sets of microsecond pulses of opposite polarity, and finally a DC signal 80 for a predetermined duration. This cycle is repeated multiple times until the treatment is complete. Or, a set of nanosecond pulses of opposite polarity can be applied first, followed by multiple sets of microsecond pulses of opposite polarity, and finally a DC signal 80 for a predetermined duration. This cycle is repeated multiple times until the treatment is complete.

[0067] Optionally, in one of the signal cycles S1, a set of second pulses 61 with opposite polarities are arranged before the DC signal 80 within a predetermined time period; or A second set of pulses 61 with opposite polarity is arranged after the DC signal 80 within a predetermined time period.

[0068] Reference Figure 8 Example Scheme 3 of this embodiment is as follows: After applying a set of nanosecond pulses with opposite polarities, a set of microsecond pulses with opposite polarities can be applied first, followed by a DC signal 80 for a predetermined time. This allows the microsecond pulses to first destroy the cell membrane, reduce tissue impedance, and make it easier for the chemical substances electrolyzed by DC to diffuse, thereby expanding the ablation range.

[0069] Reference Figure 9 Example scheme four of this embodiment is as follows: After applying a set of nanosecond pulses of opposite polarity, a DC signal 80 for a predetermined time is first applied, followed by a set of microsecond pulses of opposite polarity. This causes the DC electrolysis to first change the pH environment of the tissue, producing chemical toxicity. The microsecond pulses then further destroy the cells that have already been affected by the chemical action, which may more thoroughly remove residual cells.

[0070] Optionally, the first pulse 51 in the first embodiment of this application and the first pulse 51 and the second pulse 61 in the second embodiment are both bipolar electrical pulses.

[0071] Optionally, there may be a zero-level interval between two first pulses 51 with opposite polarities in the same group, between two second pulses 61 with opposite polarities in the same group, between the first pulse 51 and the DC signal 80, and between the second pulse 61 and the DC signal 80.

[0072] Optionally, the duration of each pulse interval is 1 ns or more. The duration of the zero-level interval between each adjacent pulse can be adjusted according to the pulse width and pulse amplitude of the two adjacent pulses. The longer the duration of the zero-level interval, the more heat accumulation can be reduced. When the duration of the zero-level interval is long enough, it can further reduce the situation that causes muscle contraction and avoid damage to the human body.

[0073] Optionally, in a third embodiment, the ablation sequence signal includes a first pulse sequence 50, a second pulse sequence 60, and a DC signal 80. The ablation sequence signal includes multiple signal periods S1, one of which includes a unipolar first pulse 51, a unipolar second pulse 61, and a DC signal 80 within a predetermined time period. There is no zero-level interval between the first pulse 51, the second pulse 61, and the DC signal 80, and there is a zero-level interval between two adjacent ablation sequence signals.

[0074] Reference Figure 10 Example Scheme 1 of this embodiment is as follows: First, a positive polarity nanosecond pulse, a positive polarity microsecond pulse, and a DC signal 80 of a predetermined time are applied sequentially to form a signal cycle S1. Then, multiple signal cycles S1 are repeated until the treatment ends. There is a zero-level region between adjacent signals. In this scheme, the polarity of adjacent signal cycles S1 is the same.

[0075] Reference Figure 11 Example Scheme 2 of this embodiment is as follows: First, a positive nanosecond pulse, a positive microsecond pulse, and a DC signal 80 of predetermined duration are sequentially applied to form a signal cycle S1. Then, a negative nanosecond pulse, a negative microsecond pulse, and a DC signal 80 of predetermined duration are sequentially applied, and the signal cycle S1 is repeated until the treatment ends. There is a zero-level region between adjacent signals. In this scheme, the polarities of adjacent signal cycles S1 are opposite.

[0076] This protocol applies a first pulse 51, a second pulse 61, and a direct current signal 80 consecutively within the same signal cycle S1 without any zero-level interval. The continuous application of the first pulse 51 and the second pulse 61 maintains a high electric field intensity, enhancing penetration into deep tissues. Under the pulse-induced state of high cell membrane permeability, the immediate application of the direct current signal 80 prevents cell membrane repair without intervals, allowing the chemical toxins to continuously act and completely inactivate the cells. This protocol enhances ablation efficiency and therapeutic effect through energy superposition, sustained action, and synergistic effects.

[0077] Reference Figures 3-11 Optionally, both the first pulse 51 and the second pulse 61 are square wave pulses.

[0078] In this application, the pulse width of the first pulse 51 is 0.5 nanoseconds to 1000 nanoseconds (inclusive of the upper limit of 1000 and the lower limit of 0.5), and the pulse amplitude is ±1 kV to 20 kV (inclusive of the upper limit of 20 and the lower limit of 1); the pulse width of the second pulse 61 is 1 microsecond to 1000 microseconds (inclusive of the upper limit of 1000 and the lower limit of 1), and the pulse amplitude is ±0 V to 5 kV (inclusive of the upper limit of 5, excluding the lower limit of 5). The voltage of the DC signal 80 is 0 V to 300 V (inclusive of the upper limit of 300, excluding the lower limit of 0), and the current is 0 mA to 250 mA (inclusive of the upper limit of 250, excluding the lower limit of 0).

[0079] Reference Figure 12 Based on the same inventive concept, this application provides an electroablation system, including the electroablation device described in the above embodiments, and a host computer 90.

[0080] In this embodiment, the host computer 90 can update the program or back up the data of the electroablation device, and can also remotely control the electroablation device, which can facilitate the functional expansion of the ablation device. Optionally, the host computer 90 can communicate with the pulse generator 20 and the DC generator 30 via WIFI (Wireless Fidelity, also known as mobile hotspot). Optionally, the host computer 90 communicates with the pulse generator 20 and the DC generator 30 via the cloud.

[0081] In this embodiment, the host computer 90 is communicatively connected to both the pulse generator 20 and the DC generator 30. The host computer 90 sends electrical signals to the pulse generator 20 and the DC generator 30 according to the pre-stored waveform design file, so that the pulse generator 20 sends electrical pulse signals to the ablation device 10 according to the preset transmission time, pulse amplitude, pulse width, and number of pulses, and the DC generator 30 sends DC electrical signals 80 to the ablation device 10 according to the preset transmission time, voltage value, and current value.

[0082] Based on the same inventive concept, this application provides a pulse control method for an electroablation device using the above embodiments, including: An electrical pulse signal and a direct current signal 80 are delivered to the ablation device 10. The electrical pulse signal is used to create nanoscale pores in the cells of the target biological tissue near the ablation device 10, and the direct current signal 80 is used to use the cytoplasm flowing out from the nanoscale pores as an electrolyte.

[0083] Optionally, the DC generator 30 may output the DC signal 80 before the pulse generator 20 outputs the electrical pulse signal; or the DC signal 80 may output the DC signal 80 after the pulse generator 20 outputs the electrical pulse signal; or the DC signal 80 and the electrical pulse signal may be output simultaneously; or the output times of the DC signal 80 and the electrical pulse signal may at least partially overlap.

[0084] The beneficial technical effects of the technical solutions provided in this application include: This application combines electroporation ablation and electrolytic ablation to create an irreversible electroporation ablation region 41, a reversible electroporation ablation region 42, and an acid-base ablation region 43 around the ablation device 10 from the inside out. Specifically, the acid-base ablation region 43 formed by the DC signal 80 surrounds the reversible electroporation region and the irreversible electroporation ablation region 41 formed by the electrical pulse signal. The nanoscale pores generated by electroporation ablation promote cytoplasmic outflow. The outflowing cytoplasm serves as the electrolyte environment for the DC signal, increasing the diffusion efficiency of electrolytic products in the DC signal 80 and raising the electrolyte concentration within the target biological tissue. This accelerates the formation of a cytotoxic environment near the first electrode 11 and the second electrode 12. The formed cytotoxic environment (acid-base ablation region 43) further promotes cell inactivation within the reversibly electroporated area of ​​the target biological tissue, accelerating apoptosis. The two ablation methods work together to complement each other, expanding the ablation range and shortening the treatment time with fewer electrodes. This is especially suitable for solid tumors with unclear boundaries or lesions adjacent to sensitive structures, reducing the tumor recurrence rate and the probability of postoperative complications. At the same time, using fewer electrodes can also reduce the physical burden on patients.

[0085] This application achieves a sufficiently strong electric field by synergizing a first pulse 51 with a larger amplitude and a second pulse 61 with a smaller amplitude. This induces the formation of more irreversible electroporation pores on the cell membrane surface, expands the perforation range of the cell membrane, accelerates cell apoptosis, and further improves the ablation effect.

[0086] By setting zero-level intervals between two adjacent first pulses 51, between two adjacent second pulses 61, between the first pulse 51 and the DC signal 80, and between the second pulse 61 and the DC signal 80, and by maintaining the zero-level intervals for a longer duration, the accumulation of heat can be reduced. When the duration of the zero-level intervals is long enough, the situation that causes muscle contraction can be reduced, thus avoiding damage to the human body.

[0087] In the description of this application, the terms "center," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," and "outer," etc., indicate directions or positional relationships based on the exemplary directions or positional relationships shown in the accompanying drawings. They are used to facilitate the description or simplification of the embodiments of this application and are not intended to indicate or imply that the device or component referred to must have a specific orientation or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application.

[0088] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this application, unless otherwise stated, "a plurality of" means two or more.

[0089] In the description of this application, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0090] In the description of this specification, specific features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or examples.

[0091] The above description is only a partial implementation of this application. It should be noted that for those skilled in the art, other similar implementation methods based on the technical concept of this application, without departing from the technical concept of this application, also fall within the protection scope of the embodiments of this application.

Claims

1. An electroablation device, characterized in that, include: An ablation device for inserting into target biological tissue, comprising at least one first electrode and at least one second electrode; A pulse generator, electrically connected to the ablation device, is used to deliver an electrical pulse signal to the ablation device. The electrical pulse signal is used to create nanoscale pores in the cell membrane of the target biological tissue. The electrical pulse signal includes at least a first pulse sequence, which includes at least one first pulse. A DC generator, electrically connected to the ablation device, is used to deliver a DC signal to the ablation device, causing the regions near the first and second electrodes to exhibit acid-base differentiation; the electrical pulse signal and the DC signal together form an ablation signal sequence.

2. The electroablation device according to claim 1, characterized in that, When the pulse generator applies an electrical pulse signal to the first electrode and / or the second electrode, an electroporation ablation region is formed in the target biological tissue. The electroporation ablation region includes an irreversible electroporation ablation region and a reversible electroporation ablation region from the inside out. At least one first electrode is disposed in the irreversible electroporation ablation region, and at least one second electrode is disposed in the electroporation ablation region; When the DC generator applies a DC signal to the first electrode and the second electrode, an acid-base ablation region covering the electroporation ablation region is gradually formed within the target biological tissue.

3. The electroablation device according to claim 1, characterized in that, The electrical pulse signal further includes a second pulse sequence, which includes at least one second pulse, wherein the amplitude of the first pulse is greater than that of the second pulse, and the width of the first pulse is less than that of the second pulse; Within one signal cycle of the ablation sequence signal, the first pulse, the second pulse, and the DC signal are arranged sequentially; or, within one signal cycle of the ablation sequence signal, the first pulse, the DC signal, and the second pulse are arranged sequentially.

4. The electroablation device according to claim 1, characterized in that, The ablation sequence signal is a signal cycle, including at least a set of first pulses with opposite polarities and a continuous DC signal; Alternatively, the ablation sequence signal may include multiple signal cycles, one of which includes at least one set of first pulses of opposite polarity and the DC signal within a predetermined time period.

5. The electroablation device according to claim 3, characterized in that, The ablation sequence signal is a signal cycle, including at least one set of first pulses with opposite polarity, at least one set of second pulses with opposite polarity, and a continuous DC signal; Alternatively, the ablation sequence signal may include multiple combined pulse sequences and a continuous DC signal, wherein the combined pulse sequences include a set of first pulses of opposite polarity and a set of second pulses of opposite polarity; Alternatively, the ablation sequence signal may include multiple signal cycles, one of which includes at least one set of first pulses of opposite polarity, at least one set of second pulses of opposite polarity, and the DC signal within a predetermined time period.

6. The electroablation device according to claim 5, characterized in that, In one of the signal cycles of the ablation sequence signal, a set of second pulses of opposite polarity is arranged before the DC signal within a predetermined time period; or A second set of pulses with opposite polarity is arranged after the DC signal within a predetermined time period.

7. The electroablation device according to claim 5, characterized in that, There are zero-level intervals between two first pulses of opposite polarity in the same group, between two second pulses of opposite polarity in the same group, between the first pulse and the DC signal, and between the second pulse and the DC signal.

8. The electroablation device according to claim 3, characterized in that, The ablation sequence signal includes multiple signal cycles, one of which includes a unipolar first pulse, a unipolar second pulse, and a DC signal within a predetermined time period. There is no zero-level interval between the first pulse, the second pulse, and the DC signal, and there is a zero-level interval between two adjacent ablation sequence signals.

9. The electroablation device according to claim 3, characterized in that, It also includes at least one of the following: The first pulse is a nanosecond pulse, and the second pulse is a microsecond pulse; The first pulse and the second pulse are square wave pulses; The pulse width of the first pulse is 0.5 nanoseconds to 1000 nanoseconds, and the pulse amplitude is ±1 kV to 20 kV. The pulse width of the second pulse is 1 microsecond to 1000 microseconds, and the pulse amplitude is ±0 volts to 5 kilovolts; The DC signal has a voltage of 0V-300V and a current of 0mA-250mA.

10. An electroablation system, characterized in that, Includes the electroablation device as described in any one of claims 1-9, and a host computer; The host computer is communicatively connected to the pulse generator and DC generator in the electroablation device.

11. A pulse control method for an electroablation device according to any one of claims 1-9, characterized in that, include: Electrical pulse signals and DC signals are delivered to the ablation device.

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