KR102293441B1 - Electroporation bipolar electrode for curing prostate cancer, electroporation device comprising the same and method for controlling the same - Google Patents

Abstract

Provided are an electroporation bipolar electrode for curing prostate cancer to minimize the size of a perforation while maximizing the scope of the incision, an electroporation device including the same, and a control method thereof. According to the present invention, the electroporation bipolar electrode for curing prostate cancer comprises: a first bipolar electrode including i) an elongated first body, ii) a first electrode formed on the surface of the first body, and iii) a second electrode spaced apart from the first electrode in the longitudinal direction of the first body and formed on the surface of the first body; and a second bipolar electrode including i) an elongated second body, ii) a third electrode formed on the surface of the second body, and iii) a fourth electrode spaced apart from the third electrode in along the longitudinal direction of the second body and formed on the surface of the second body. A voltage is applied to each of one or more pairs of electrodes selected from a group consisting of the first electrode, the second electrode, the third electrode, and the fourth electrode to form a bipolar electric field network.

Description

Bipolar electrode unit for electroporation for treatment of prostate cancer, electroporation device including same, and control method thereof

The present invention relates to a bipolar electrode unit for electroporation, a method for controlling the same, and an electroporation apparatus including the same. More particularly, it relates to a bipolar electrode unit for electroporation for the treatment of prostate cancer, a method for controlling the same, and an electroporation apparatus including the same.

A tumor refers to cells in the body that have developed excessively with autonomy. Tumors develop independently of the totality of the individual. Tumors are divided into malignant tumors and benign tumors, and malignant tumors are called cancers. Since benign tumors are not cancerous, there is no big problem if they are resected according to the site.

In order to treat a tumor, a surgical method of excising a tumor, a method of destroying tissue by exposing a tumor to radiation, and a method of necrosis of cancer cells, which are malignant tumors, are used by administering an anticancer agent. For early cancers, surgical resection of the tumor can be used. However, surgical methods carry risks for malignant tumors, and radiation therapy or chemotherapy is effective for early cancer but not as effective for malignant tumors. Moreover, since the patient's immunity is lowered and the body becomes weak, it cannot be applied to the weak patients. Therefore, an electroporation method that can replace it is being used. In the electroporation method, a high voltage is applied to direct the lipid to one side to form a perforation in the cell membrane. The perforations may be refilled according to the strength of an applied voltage, and a case in which perforations generated by the voltage are not refilled over time is referred to as irreversible electroporation. In the irreversible electroporation method, cells are necrotic by electrically perforating the target cells so that they cannot be recovered. That is, in the irreversible electroporation method, irreversible electricity is applied to the target cells to cause necrosis of the target cells.

Provided is a bipolar electrode unit for electroporation for the treatment of prostate cancer. Also provided is a method for controlling a bipolar electrode unit for electroporation. And it provides an electroporation device comprising a bipolar electrode unit for electroporation.

The bipolar electrode unit for electroporation for the treatment of prostate cancer according to an embodiment of the present invention includes a first bipolar electrode and a second bipolar electrode. The first bipolar electrode includes i) a first body elongated, ii) a first electrode formed on the surface of the first body, and iii) spaced apart from the first electrode along the longitudinal direction of the first body to be on the surface of the first body and a second electrode formed thereon. The second bipolar electrode includes i) a second body extending elongated, ii) a third electrode formed on the surface of the second body, and iii) spaced apart from the third electrode along the longitudinal direction of the second body and on the surface of the second body and a formed fourth electrode. A voltage may be applied to each of one or more pairs of electrodes selected from the group consisting of the first electrode, the second electrode, the third electrode, and the fourth electrode to form a bipolar electric field network in the one or more pairs of electrodes.

The first body may include i) an elongated straight body part, and ii) an oblique body part connected at an angle to the straight body part. The second body includes: i) another elongated straight body part, and ii) another oblique body part connected at an angle to another straight body part and gradually increasing the distance from the oblique body part toward the prostate cancer. may include wealth. The distance between the first electrode and the second electrode or the distance between the third electrode and the fourth electrode may be 4 mm to 10 mm. At least one electrode selected from the group consisting of the first electrode, the second electrode, the third electrode, and the fourth electrode may have a length of 2 mm to 6 mm.

The electroporation apparatus according to an embodiment of the present invention includes: i) the above-described bipolar electrode unit for electroporation, ii) a power supply unit, iii) a voltage generating unit receiving power from the power supply unit to generate a voltage, and iv) a second and a control unit that controls to apply a voltage to the first electrode, the second electrode, the third electrode, and the fourth electrode. The control unit includes a first switch, a second switch, a third switch, a fourth switch, and a bridge circuit including a bridge line. The first switch and the second switch are electrically connected in series, the third switch and the fourth switch are electrically connected in series, and the first switch and the second switch are electrically connected in parallel with the third switch and the fourth switch. . The bridge line electrically connects between the first switch and the second switch and between the third switch and the fourth switch.

The control unit may further include i) a first grounding switch provided between the first switch and the second switch, and ii) a second grounding switch provided between the third switch and the fourth switch. The control unit may control the first switch, the second switch, the third switch, and the fourth switch to provide a positive voltage pulse or a negative voltage pulse to the prostate cancer. The positive voltage pulse or the negative voltage pulse includes group pulses, respectively, the voltage of the positive voltage pulse or the negative voltage pulse is 700V to 3000V, and the pulse width of the positive voltage pulse or the negative voltage pulse is 100 µs to 1000 μs, the pulse delay of the positive voltage pulse or the negative voltage pulse is 100 μs to 2000 μs, the number of pulses of the positive voltage pulse or the negative voltage pulse is 1 to 20, the number of group pulses is The delay of 1 to 5, and group pulses may be 100 μs to 2000 μs.

The control unit includes: i) a fifth switch corresponding to the first switch, ii) a sixth switch corresponding to the second switch, iii) a seventh switch corresponding to the third switch, iv) an eighth switch corresponding to the fourth switch a switch, v) another bridge wire corresponding to the bridge wire, vi) a third grounding switch provided between the fifth switch and the sixth switch, and vii) a fourth grounding switch provided between the seventh switch and the eighth switch. It may further include another bridge circuit including: Another bridge circuit may be electrically coupled to the bridge circuit.

In the method for controlling a bipolar electrode unit for electroporation according to an embodiment of the present invention, i) a first switch and a fourth switch are turned on, and a positive voltage pulse is applied to the prostate cancer by turning off the second switch and the third switch a first step of, ii) turning off the first switch, the second switch, the third switch, and the fourth switch, respectively, and a second step of turning on the second grounding switch, iii) turning off the second grounding switch, and the second a third step of applying a negative voltage pulse to the prostate cancer by turning on the switch and the third switch, and turning off the first switch and the fourth switch, and iv) the first switch, the second switch, the third switch and the fourth and a fourth step of turning off each switch and turning on the first ground switch. The first step or the third step is performed for 0.5 μs to 2 μs.

The second step may be performed for 2 μs to 7 μs. The method for controlling a bipolar electrode unit for electroporation according to an embodiment of the present invention may further include a fifth step in which an electric field is formed between the first electrode and the second electrode by repeating the first to fourth steps. . The method of controlling a bipolar electrode unit for electroporation according to an embodiment of the present invention may further include a fifth step of repeating the first to fourth steps for the second bipolar electrode unit.

The control method of the bipolar electrode unit for electroporation according to an embodiment of the present invention includes i) a first step of turning on the first switch and the sixth switch, and turning off all the remaining switches to apply a positive voltage pulse to the prostate cancer , ii) a second step of turning off the first and sixth switches and turning on the third grounding switch, iii) turning off the third grounding switch, and turning on the fifth and second switches to generate negative voltage pulses a third step of applying to the arm, and iv) a fourth step of turning off the fifth switch and the second switch and turning on the first ground switch.

The control method of the bipolar electrode unit for electroporation according to an embodiment of the present invention includes: i) the first ground switch is turned off, the third switch and the eighth switch are turned on to apply a positive voltage pulse to the prostate cancer Step 5, ii) a sixth step of turning off the third and eighth switches and turning on the fourth grounding switch, iii) turning off the fourth grounding switch, and turning on the seventh and fourth switches to generate a negative voltage pulse It may further include a seventh step of applying to prostate cancer, and iv) an eighth step of turning off the seventh and fourth switches and turning on the second grounding switch.

The method of controlling a bipolar electrode unit for electroporation according to an embodiment of the present invention may further include a ninth step of forming a bipolar network electric field between the first electrode and the third electrode, and the second electrode and the fourth electrode. have.

The method for controlling a bipolar electrode unit for electroporation according to an embodiment of the present invention includes i) a first step of turning on the fifth switch and the fourth switch, and turning off all the remaining switches to apply a positive voltage pulse to the prostate cancer , ii) a second step of turning off the fifth and fourth switches and turning on the second grounding switch, iii) turning off the second grounding switch, and turning on the third and sixth switches to generate negative voltage pulses a third step of applying to the arm, and iv) a fourth step of turning off the first switch and the eighth switch and turning on the third ground switch.

The control method of the bipolar electrode unit for electroporation according to an embodiment of the present invention comprises: i) turning off the third ground switch and turning on the first switch and the eighth switch to apply a positive voltage pulse to the prostate cancer Step 5, ii) a sixth step of turning off the first switch and the eighth switch and turning on the fourth grounding switch, iii) turning off the fourth grounding switch, and turning on the seventh switch and the second switch to generate a negative voltage pulse It may further include a seventh step of applying to prostate cancer, and iv) an eighth step of turning off the seventh switch and the second switch and turning on the first grounding switch. The method of controlling a bipolar electrode unit for electroporation according to an embodiment of the present invention may further include a ninth step of forming a bipolar network electric field between the first electrode and the fourth electrode, and the second electrode and the third electrode. have.

By using a bipolar electrode unit for electroporation for prostate cancer treatment, it is possible to maximize the incision range while minimizing the puncture size of prostate cancer cells. That is, since various types of electric fields are repeatedly formed, the killing effect of prostate cancer can be enhanced by maximizing the accumulation of electric energy. In addition, it is possible to easily kill the prostate cancer by accurately positioning the bipolar electrode unit for electroporation for the treatment of prostate cancer.

1 is a schematic diagram of the prostate and its surrounding organs.
2 is a schematic diagram of an electrode for electroporation for treatment of prostate cancer according to a first embodiment of the present invention.
3 is a schematic diagram of an electroporation electrode for the treatment of prostate cancer according to a second embodiment of the present invention.
FIG. 4 is a schematic block diagram of an electroporation apparatus including an electroporation electrode for the treatment of prostate cancer of FIG. 1 .
5 is a schematic block diagram of an electroporation apparatus including the electrode of FIG. 1 .
6 is a schematic diagram of various pulse graphs applied by the electroporation apparatus of FIG. 5 and a bridge circuit corresponding thereto.
7 to 9 are schematic views of various operating processes of a voltage pulse graph of a bipolar electrode unit for electroporation according to an embodiment of the present invention and a bridge circuit inducing the same.
10 is an electric field distribution diagram formed in bipolar electrodes according to the simulations of Experimental Examples 1 to 3 of the present invention.
11 shows a monophase pulse using a monopolar electrode and a biphase pulse using the bipolar electrode of the present invention.
12 is a result of an experiment of hematoxylin eosin (H&E staining) using the pulses of FIG. 11 (a) to (d).
13 is a result of TUNEL ((Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End-Labeling) staining experiment using the pulses of FIG. 11 (a) to (d).
14 is a graph comparing the TUNEL ablation area and muscle contraction when the pulses of FIGS. 11 (a) to (d) are used.
15 is a graph comparing hepatocyte necrosis and apoptotic cells when the pulses of FIGS. 11 (a) to (d) are used.
16 is a result of an experiment of immunohistochemistry (IHC) HMGB-1 in the case of using the pulses of FIGS. 11 (a) to (d).
17 is a result of an immunohistochemistry (IHC) IL-6 experiment using the pulses of FIGS. 11 (a) to (d).
18 is a graph comparing the results of immunohistochemistry (IHC) HMGB-1 and IL-6 when the pulses of FIGS. 11 (a) to (d) are used.

The terminology used herein is for the purpose of referring to specific embodiments only, and is not intended to limit the invention. As used herein, the singular forms also include the plural forms unless the phrases clearly indicate the opposite. The meaning of "comprising," as used herein, specifies a particular characteristic, region, integer, step, operation, element and/or component, and other specific characteristic, region, integer, step, operation, element, component, and/or group. It does not exclude the existence or addition of

Although not defined otherwise, all terms including technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention belongs. Commonly used terms defined in the dictionary are additionally interpreted as having a meaning consistent with the related technical literature and the presently disclosed content, and unless defined, they are not interpreted in an ideal or very formal meaning.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those of ordinary skill in the art can easily carry out the embodiments of the present invention. However, the present invention may be embodied in many different forms and is not limited to the embodiments described herein.

1 schematically shows the prostate and its surrounding organs. The prostate is the male reproductive organ about the size of a chestnut in the front of the rectum just below the bladder. The prostate surrounds the urethra. The prostate makes and stores part of the semen. Most of the prostate cancers are adenocarcinomas that arise from prostate cells. Prostate cancer is uncommon before the age of 50, but increases rapidly after the age of 50. Since prostate cancer metastasizes well to bone, it inevitably progresses from an androgen-dependent state to an androgen-resistant state, increasing the patient's mortality. In particular, since a large number of prostate cancer, that is, tumor cells are scattered in the prostate, it is necessary to fundamentally remove them. Therefore, it is removed using an irreversible electroporation method.

2 schematically shows a bipolar electrode unit 100 for electroporation for treatment of prostate cancer according to a first embodiment of the present invention. The bipolar electrode unit 100 for electroporation of FIG. 2 includes a pair of bipolar electrodes 110 and 130 . The pair of bipolar electrodes 110 and 130 includes a first bipolar electrode 110 and a second bipolar electrode 130 .

The first bipolar electrode 110 includes a first body 10 , a first electrode 20 , and a second electrode 30 . The first body 10 is elongated. That is, the first body 10 has a shape extending toward the tumor cell (T) so as to penetrate the tumor cell (T). The first electrode 20 is formed on the surface of the first body 10 . The second electrode 30 is spaced apart from the first electrode 20 in the longitudinal direction of the first body 10 . The second electrode 30 is also formed on the surface of the first body 10 . The first electrode 20 and the second electrode 30 are collectively referred to as bipolar.

The second bipolar electrode 130 includes a second body 13 , a third electrode 23 , and a fourth electrode 33 . The second body 13 is elongated. That is, the second body 13 has a shape extending toward the tumor cell (T) so as to penetrate the tumor cell (T). The third electrode 23 is formed on the surface of the second body 13 . The fourth electrode 33 is spaced apart from the third electrode 23 along the longitudinal direction of the second body 13 . The fourth electrode 33 is also formed on the surface of the second body 13 . The third electrode 23 and the fourth electrode 33 are also collectively referred to as bipolar. Accordingly, the first bipolar electrode 110 and the second bipolar electrode 130 form a bipolar network. In the bipolar network, various types of electric fields are repeatedly formed, so that it is possible to maximize the accumulation of electric energy to increase the treatment efficiency of tumor cells.

Conventionally, monopolar electrodes have been used to treat tumor cells. In this case, there is a problem that the number of perforations is too large because the area of the electrode is large. On the contrary, in an embodiment of the present invention, the number of perforations is reduced by half by using a bipolar electrode, thereby reducing side effects of bleeding. In addition, by forming a bipolar network electric field, the cut-out range is formed larger than that of the monopolar electrode. Therefore, it is possible to promote the death of tumor cells by maximizing the effect of dissection of tumor cells.

The electrodes 20 , 30 , 23 , and 33 are formed by masking the first body 10 and the second body 13 and plating with a conductive metal by sputtering or the like. As the conductive metal, one of platinum, tin, chromium, zinc, pure gold, and copper may be used, or an alloy in which a plurality of materials are mixed may be prepared and used.

The separation distance D between the electrodes 20 and 30 formed on the same first bipolar electrode 110 may be 4 mm to 10 mm. Although not shown in FIG. 2 , the distance between the electrodes 23 and 33 is also the same. When the separation distance D between the electrodes 20 and 30 is too large or too small, it is difficult to efficiently generate a bipolar electric field network. Therefore, it is preferable to maintain the separation distance D of the electrodes 20 and 30 in the above-described range.

Meanwhile, the length L of one or more of the electrodes 20 , 30 , 23 , and 33 may be 2 mm to 6 mm. If the length L of the electrode is too small or too large, it is difficult for the bipolar electric field network to work efficiently. Therefore, the length (L) of the electrode maintains the above-described range. And the width of the main bodies (10, 13) may be 2mm.

The magnitude of the electric field applied to the electrodes 20 , 30 , 23 , 33 is proportional to their electrical conductivity. Therefore, Equation 1 below is established, and the electric field below is generated between the electrodes 20, 30, 23, and 33. Here, an electric field network may be formed by combining various electrodes A1-B1, A1-A2, A1-B2, B1-A2, B1-B2, and A2-B2.

E denotes an electric field, σ denotes electrical conductivity, A1 denotes the first electrode 20 , B1 denotes the second electrode 30 , A2 denotes the third electrode 23 , and B2 denotes the fourth electrode 33 .

When an electric field of a specific intensity or more is applied to the tumor cells (T), the moisture of the tumor cells (T) is electrolyzed and the tumor cells (T) are subjected to physical stress. That is, when an electric field of a specific intensity or more is applied to the tumor cells T, the water molecules are electrolyzed into hydrogen and oxygen and the necrosis of the tumor cells T proceeds for a certain period of time. An electric field is applied to the tumor cell T by applying a voltage in the form of a pulse to the pair of electrodes 20 , 30 , 23 , and 33 . In this case, the tumor cells (T) have the ability to adapt and get used to the electric field, so they can act as a defense. For example, in tumor cells (T), potassium ions (K ⁺ ), which are essential for regulating intracellular metabolism, are present. When a perforation occurs in the cell membrane, potassium ions flow out of the cell through the perforation. Tumor cells (T) whose intracellular potassium concentration becomes abnormal due to leakage of potassium ions to the outside receives a signal leading to apoptosis from a receptor on the cell membrane and dies. Apoptosis by such irreversible electroporation can be applied to tumor cells (T).

In the first embodiment of the present invention, a plurality of electrodes 20 , 30 , 23 , and 33 are used instead of one electrode. In this case, a bipolar network electric field is formed between the electrodes 20, 30, 23, and 33 to maximize the ablation area of the tumor cell T and reduce perforation. As a result, the possibility of death of the tumor cells (T) can be increased. In addition, since it is much easier to position the electrodes 20 , 30 , 23 , and 33 on the tumor cell T, the operation is simplified. Furthermore, in the first embodiment of the present invention, it is possible to more easily kill the tumor cells (T) by the hybrid effect in which the heat treatment is added as well as the formation of the bipolar network electric field. That is, since the tumor cells (T) are affected not only by irreversible electroporation but also by heat, the therapeutic effect can be maximized. On the other hand, when only one electrode is used, the resection area of the tumor cells (T) is reduced. As a result, the killing effect of the tumor cells (T) may be reduced. This will be described in more detail with reference to FIG. 3 .

3 schematically shows an operating mechanism of the bipolar electrode unit 100 for electroporation of FIG. 1 . The operating mechanism of the bipolar electrode unit 100 for electroporation of FIG. 3 is only for illustrating the present invention, and the present invention is not limited thereto. Therefore, the bipolar electrode unit 100 for electroporation may operate by other mechanisms.

_{As shown in Fig. 3, the impedances (G 1} , G ₂ , G ₃ , ...) act by various combinations of the electrodes (20, 30, 23, 33) (shown in Fig. 2) while the tumor cell ( T) a bipolar network electric field is formed around it. As a result, tumor cells (T) lead to apoptosis. The time taken for apoptosis (t) is proportional to the time (t) for which the electric field (E) is applied.

4 schematically shows a bipolar electrode unit 200 for electroporation for treating prostate cancer according to a second embodiment of the present invention. The bipolar electrode unit 200 for electroporation of FIG. 4 includes a first bipolar electrode 120 and a second bipolar electrode 140 . Since the structure of the bipolar electrode unit 200 for electroporation of FIG. 4 is similar to the structure of the bipolar electrode unit 100 for electroporation of FIG.

4 , the first bipolar electrode 120 includes a first body 12 , a first electrode 20 , and a second electrode 30 . The first body 12 is elongated. That is, the first body 12 has a shape extending toward the tumor cell (T) so as to penetrate both sides of the tumor cell (T). The second bipolar electrode 140 includes a second body 14 , a third electrode 23 , and a fourth electrode 33 . The second body 14 is elongated. That is, the second body 14 has a shape extending toward the tumor cell (T) so as to penetrate both sides of the tumor cell (T).

The first body 12 includes a straight body part 121 and an oblique body part 123 , and the second body 14 includes a straight body part 141 and an oblique body part 143 . The straight body parts 121 and 141 extend long toward the tumor cell T. The oblique body parts 123 and 143 are connected while forming an angle with the straight body parts 121 and 141, respectively. The oblique body parts 123 and 143 are formed to gradually increase a distance from each other while facing the prostate cancer. Since the bipolar electrodes 120 and 140 have such a structure, the bipolar electrodes 120 and 140 can be disposed on both sides of the tumor cell T to easily kill the tumor cell T. That is, a bipolar network electric field may be formed by the bipolar electrodes 120 and 140 to cause the tumor cell T to commit suicide.

5 schematically shows a block diagram of an electroporation apparatus 1000 according to an embodiment of the present invention. The block diagram of FIG. 5 is merely for illustrating the present invention, and the present invention is not limited thereto. Accordingly, the block diagram of FIG. 5 may be modified into other forms.

As shown in FIG. 5 , the electroporation apparatus 1000 includes bipolar electrode units 100 and 200 , a connector 300 , a control unit 400 , a voltage generating unit 500 , a relay switch 600 , and a power source. unit 700 . In addition, the electroporation apparatus 1000 may further include other components.

A bipolar network is formed in the bipolar electrode units 100 and 200 by a voltage pulse applied by the voltage generating unit 500 . The voltage pulse is converted into positive or negative by switching of the bipolar electrode units 100 and 200 and is applied. The voltage generating unit 500 generates a voltage pulse of a preset size using the rated power supplied from the power unit 700 . The voltage generating unit 500 may generate a voltage pulse by varying it with a preset step size. For example, a specific voltage pulse may be generated by dividing the steps within a voltage range of 700V to 3000V. The generated voltage pulse is supplied to the relay switch 600 .

The relay switch 600 supplies the voltage pulse generated by the voltage generating unit 500 to the connector 300 under the control of the control unit 400 . The voltage pulse supplied to the connector 300 is applied to the bipolar electrode units 100 and 200 .

The control unit 400 controls the relay switch 600 to selectively supply voltage pulses to the bipolar electrode units 100 and 200 . The control unit 400 may set and apply a voltage pulse to the bipolar electrode units 100 and 200 at a preset period. That is, the voltage pulse may be switched to be positively or negatively converted and applied. This will be described in more detail with reference to FIG. 6 .

6 shows various pulse graphs applied by the electroporation apparatus 1000 of FIG. 5 and a bridge circuit 800 corresponding thereto. Figure 6 (a) shows a positive voltage pulse and the operation state of the bridge circuit 800 for generating the same, Figure 6 (b) and (d) shows the ground state, Figure 6 (c) is It shows the operation state of the negative voltage pulse and the bridge circuit 800 for generating it. The pulse graph of FIG. 6 and the operation state of the bridge circuit 800 are merely for illustrating the present invention, and the present invention is not limited thereto. Accordingly, the pulse graph of FIG. 6 and the operating state of the bridge circuit 800 may be modified into other forms. Meanwhile, the bridge circuit 800 may be included in the control unit 400 (shown in FIG. 5 ).

As shown in FIG. 6 , the bridge circuit 800 is an H-type and includes a bridge line 401 and four switches 201 , 301 , 231 , and 331 . Each of the switches 201 , 301 , 231 , and 331 is dividedly positioned on the top, bottom, left, and right of the bridge circuit 800 , and corresponds to the electrodes 20 , 30 , 23 , 33 (shown in FIG. 2 ), respectively. The first switch 201 and the second switch 301 are electrically connected in series. The third switch 231 and the fourth switch 331 are electrically connected in series. In addition, the first switch 201 and the second switch 301 and the third switch 231 and the fourth switch 331 are electrically connected in parallel to each other. The bridge line 401 electrically connects between the first switch 201 and the second switch 301 and between the third switch 231 and the fourth switch 331 . The first ground switch 801 is electrically connected between the first switch 201 and the second switch 301 , and the second ground switch 803 is located between the third switch 231 and the fourth switch 331 . ) are electrically connected between When the first grounding switch 801 and the second grounding switch 803 are turned on, the excitation electrical energy remaining through the grounding may be removed.

As shown in (a) of FIG. 6, when the switches 201 and 331 are turned on and the switches 231 and 301 are turned off, a current flows in the direction of the arrow and a positive voltage pulse is supplied while the bipolar network electric field is applied to tumor cells. Therefore, it induces the electroporation of the tumor cells and promotes the death of the tumor cells.

Next, as shown in (b) of FIG. 6, all the switches 201, 301, 231, and 331 are turned off to make the voltage pulse 0. And the bridge circuit 800 is grounded. That is, when the second ground switch 803 is turned on, the electric energy of the excitation around the fourth switch 331 is completely removed through the ground. Therefore, the floating phenomenon can be prevented. In addition, side effects such as muscle contraction and cardiac fibrillation can be prevented. On the other hand, the first grounding switch 801 is blocked by the non-conductive tumor cells (T) close to the grounding effect.

And as shown in (c) of FIG. 6, the second ground switch 803 is turned off, and the switches 201 and 331 are turned off, and the switches 231 and 301 are turned off, as opposed to (a) of FIG. When turned ON, current flows in the direction of the arrow and a bipolar network electric field with negative voltage pulses is formed. When bipolar electrodes are located on both sides of the tumor cell (T) and only positive voltage is applied, (+) charges on one side and (-) charges on the other side continue to accumulate, making it difficult to induce apoptosis of the tumor cells. However, since both charges can be eliminated through this switching, tumor cells can be more easily killed.

Finally, as shown in (d) of FIG. 6 , when all switches 201 , 301 , 231 , 331 are turned OFF and the first ground switch 801 is turned ON, the second switch 301 is around of excitation electrical energy can be removed. A bipolar network electric field is applied to the tumor cells (T) while each of these steps is repeated in units of several μs.

Hereinafter, the switches 201, 203, 301, 303, 231, 233, 331, 333 of the bridge circuits 800 and 810 are controlled with reference to FIGS. 7 to 10 to form a bipolar network electric field. The creation process will be described in more detail.

7 schematically shows a voltage pulse graph of a bipolar electrode unit for electroporation according to an embodiment of the present invention, a bridge circuit inducing the same, and an operation process of the bipolar electrode unit. The voltage pulse graph, the bridge circuit, and the operation process of the bipolar electrode unit are merely illustrative of the present invention, and the present invention is not limited thereto. Therefore, the operation process of the voltage pulse graph, the bridge circuit, and the bipolar electrode unit can be modified into other forms. Meanwhile, each step of FIG. 7 corresponds to each step of FIG. 6 . Therefore, in FIG. 7 , the detailed description thereof is omitted and the waveform of several voltage pulses applied within 1 second will be mainly described.

In steps (1) and (2) of FIG. 7, a positive voltage pulse is applied. In steps (1) and (2) of FIG. 7 , a positive voltage pulse may be applied for 0.5 μs to 2 μs. That is, the pulse width is very short, about 0.5 μs to 2 μs. Next, in step (3) of FIG. 7, all charges accumulated in the bridge circuit are erased without applying a pulse through the grounding process. In this case, the second ground switch is used, and the OFF of the ground switch is made for 2 μs to 7 μs. It is possible to erase the accumulated charges only when the OFF time of the second ground switch maintains the above-mentioned range. Next, in steps (4) and (5), the switching is reversed and a negative voltage pulse is applied. Then, by turning on the first grounding switch through step (6) and grounding, the excitation electric energy is removed. This process can be repeated several times in the form of group pulses within 1 second. This process may be performed for the first bipolar electrode 110 (shown in FIG. 2 ), and the same process may be repeated for the second bipolar electrode 130 (shown in FIG. 2 ). In this case, a bipolar network electric field is formed between the electrodes of each bipolar electrode.

Specific specifications of these voltage pulses will be described as follows. For example, the voltage is 700 V to 3000 V, the pulse width is 100 μs to 1000 μs, the pulse delay is 100 μs to 2000 μs, the number of pulses is 1 to 20, the number of group pulses is 1 to 5, and the group pulse delay is 100 μs to 2000 μs.

A conventional monopolar electrode generates a voltage pulse by turning ON/OFF only one switch connected in series. Therefore, a single-phase square wave pulse was formed. However, in this case, there were side effects of muscle contraction and induction of cardiac fibrillation. That is, even if the switch is turned OFF and a voltage pulse is not applied, there is a problem in that the muscles contract or cardiac fibrillation occurs due to the electric energy of the excitation. On the contrary, in an embodiment of the present invention, the above-mentioned side effect can be eliminated by using a bridge-type circuit capable of being grounded. That is, it is possible to remove the electrical energy of the excitation by creating a switching circuit to enable grounding during the transition from the positive voltage pulse to the negative voltage pulse. As a result, it is possible to effectively kill the prostate cancer by maximizing the incision of the prostate cancer, and it is possible to eliminate the side effects of muscle contraction and cardiac fibrillation inducing in the prior art.

8 schematically shows a voltage pulse graph of a bipolar electrode unit for electroporation according to another embodiment of the present invention, a pair of bridge circuits inducing the same, and an operation process of the bipolar electrode unit. The parenthesis numbers of the pair of bridge circuits of FIG. 8 correspond to the parenthesis numbers of the voltage pulse graph of FIG. 8 . That is, to generate a voltage pulse graph, the switches included in the pair of bridge circuits are operated according to the parentheses number. The voltage pulse graph, the bridge circuit, and the operation process of the bipolar electrode unit are merely illustrative of the present invention, and the present invention is not limited thereto. Therefore, the operation process of the voltage pulse graph, the bridge circuit, and the bipolar electrode unit can be modified into other forms. Meanwhile, each step of FIG. 8 is similar to each step of FIG. 7 . Accordingly, in FIG. 8 , detailed descriptions of the same or similar parts are omitted, and reference numerals of the switches included in the first bridge circuit 800 are omitted for convenience.

As shown in FIG. 8 , a bipolar network electric field crossing each electrode of the pair of bipolar electrodes may be formed using a pair of bridge circuits 800 and 810 . The process will be described with reference to FIG. 8 as follows.

As shown by a thick dotted line in FIG. 8 , in steps (1) and (2), the first switch and the sixth switch 303 are first turned on. Then, all other switches are turned OFF to apply a positive voltage pulse to the tumor cells.

Next, the first switch and the sixth switch 303 are turned OFF. As a result, all switches are OFF. In step (3), the third ground switch 805 is turned on.

Then, the third ground switch 805 is turned OFF. As shown by the thin dashed-dotted line, the fifth switch 203 and the second switch are turned on in steps (4) and (5) to apply a negative voltage pulse to the tumor cells.

Next, the fifth switch 203 and the second switch are turned OFF. And in step (6), the first ground switch is turned on to remove the excited electrical energy around the second switch. This completes one cycle of the voltage pulse.

And, although not shown as a line in FIG. 8, first, the first grounding switch is turned OFF. In steps (7) and (8), the third switch and the eighth switch 333 are turned on to apply a positive voltage pulse to the tumor cells.

Next, the third switch and the eighth switch 333 are turned OFF. In step (9), the fourth ground switch 807 is turned on to remove the excitation electrical energy around the eighth switch 333 .

Then, the fourth ground switch 807 is turned OFF. Then, the seventh switch 233 and the fourth switch are turned on in steps (10) and (11) to apply a negative voltage pulse to the tumor cells.

Finally, the seventh switch 233 and the fourth switch are turned OFF. And in step (12), the second ground switch is turned on to remove the excitation electrical energy around the fourth switch.

9 schematically shows a voltage pulse graph of a bipolar electrode unit for electroporation according to another embodiment of the present invention, a pair of bridge circuits inducing the same, and an operation process of the bipolar electrode unit. The parenthesis numbers of the pair of bridge circuits of FIG. 9 correspond to the parenthesis numbers of the voltage pulse graph of FIG. 9 . That is, to generate a voltage pulse graph, the switches included in the pair of bridge circuits are operated according to the parentheses number. The voltage pulse graph, the bridge circuit, and the operation process of the bipolar electrode unit are merely illustrative of the present invention, and the present invention is not limited thereto. Therefore, the operation process of the voltage pulse graph, the bridge circuit, and the bipolar electrode unit can be modified into other forms. Meanwhile, each step of FIG. 9 is similar to each step of FIG. 8 . Accordingly, in FIG. 9 , detailed descriptions of the same or similar parts are omitted, and reference numerals of the switches included in the first bridge circuit 800 are omitted for convenience.

As shown in FIG. 9 , a bipolar network electric field crossing between upper and lower electrodes of a pair of bipolar electrodes may be formed using a pair of bridge circuits 800 and 810 . That is, the bipolar network electric field is formed by oblique crossing. The process will be described with reference to FIG. 9 as follows.

First, as shown by a thick dotted line in FIG. 9 , the fifth switch 203 and the fourth switch are turned on in steps (1) and (2). All other switches are turned OFF to apply a positive voltage pulse to the tumor cells.

Next, the fifth switch 203 and the fourth switch are turned OFF. Then, the second ground switch is turned on to remove the excited electrical energy around the fourth switch.

Then, the second grounding switch is turned OFF. As shown by the thin dashed-dotted line in FIG. 9 , in steps (4) and (5), the third switch and the sixth switch 303 are turned on to apply a negative voltage pulse to the tumor cells.

Next, the third switch and the sixth switch 303 are turned OFF. And in step (6), the third ground switch 805 is turned on to remove the excitation electric energy around the sixth switch 303 .

Then, the third ground switch 805 is turned OFF. Although not shown as a line in FIG. 9, in steps (7) and (8), the first switch and the eighth switch 333 are turned on to apply a positive voltage pulse to the tumor cells.

Next, the first switch and the eighth switch 333 are turned off. In step (9), the fourth ground switch 807 is turned on to remove the excitation electrical energy around the eighth switch 333 .

Then, the fourth ground switch 807 is turned OFF. In steps (10) and (11), the seventh switch 233 and the second switch are turned on to apply a negative voltage pulse to the tumor cells.

Finally, the seventh switch 233 and the second switch are turned OFF. In step (12), the first grounding switch is turned on to remove the excited electrical energy around the second switch.

Hereinafter, the present invention will be described in more detail through experimental examples. These experimental examples are only for illustrating the present invention, and the present invention is not limited thereto.

Experimental example

A simulation experiment was performed using a virtual bipolar electrode. The width of the virtual bipolar electrode was 2 mm, and the length of each electrode that was coated on the main body and spaced apart from each other was 4 mm. The spacing of the electrodes was 6 mm. A voltage was applied to the bipolar electrode while changing the strength of the applied voltage. Since the rest of the experimental process can be easily understood by a person skilled in the art to which the present invention pertains, a detailed description thereof will be omitted.

Experimental Example 1

A voltage of 1000 V was applied to the bipolar electrode. And the electric field formed around the bipolar electrode was simulated.

Experimental Example 2

A voltage of 1500 V was applied to the bipolar electrode. And the electric field formed around the bipolar electrode was simulated.

Experimental Example 3

A voltage of 2000 V was applied to the bipolar electrode. And the electric field formed around the bipolar electrode was simulated.

Experiment result

10 shows the distribution of the electric field formed in the bipolar electrode according to the simulation of Experimental Examples 1 to 3 of the present invention. The electric field gradually weakens in the order of red, yellow, green, blue, and violet. That is, it can be seen that the electric field appears the strongest at the electrode, and the electric field becomes weaker as it leaves the electrode. That is, it was confirmed that the bipolar network electric field was formed by the electrodes.

Next, when a monophasic pulse using a monopolar electrode is applied at a low frequency, when a biphasic pulse using the bipolar electrode of the present invention is applied at a low frequency, a biphase using the bipolar electrode of the present invention In the case of applying a pulse at a low voltage and high frequency, an experiment was performed on a case where a biphase pulse using the bipolar electrode of the present invention was applied at a high voltage and high frequency. This will be described with reference to FIGS. 11 to 18 .

11 shows a monophase pulse using a monopolar electrode and a biphase pulse using the bipolar electrode of the present invention.

11A is a low-frequency monophase pulse using a monopolar electrode. The voltage is 1600 V/cm, the pulse width is 100 μs, the pulse delay is 100 μs, and the number of pulses is 20. 11(b) is a low-frequency bi-phase pulse using the bipolar electrode of the present invention. The voltage is 1600 V/cm, the pulse width is 100 μs, the pulse delay is 100 μs, and the number of pulses is 20. 11( c ) is a low-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention. The voltage is 1600 V/cm, the pulse width is 10 μs, the pulse delay is 10 μs, and the number of pulses is 200. 11(d) is a high-voltage, high-frequency biphase pulse using the bipolar electrode of the present invention. The voltage is 3200 V/cm, the pulse width is 10 μs, the pulse delay is 10 μs, and the number of pulses is 50.

12 is a result of an experiment of hematoxylin eosin (H&E staining) using the pulses of FIG. 11 (a) to (d).

FIG. 12(a) is a result of experimenting with hematoxylin eosin (H&E staining) with a monophase pulse using a low-frequency monopolar electrode. Figure 12 (b) is a result of an experiment of hematoxylin eosin (H&E staining) with a low-frequency bi-phase pulse using the bipolar electrode of the present invention. 12( c ) is a result of an experiment on hematoxylin eosin (H&E staining) with a low-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention. FIG. 12(d) is a result of experimenting with hematoxylin eosin (H&E staining) with a high-voltage, high-frequency bi-phase pulse using the bipolar electrode of the present invention.

13 is a result of TUNEL ((Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End-Labeling) staining experiment using the pulses of FIG. 11 (a) to (d).

13A is a result of TUNEL staining experiment with a low-frequency monophase pulse using a monopolar electrode. 13(b) is a result of TUNEL staining experiment using a low-frequency bi-phase pulse using the bipolar electrode of the present invention. FIG. 13(c) is a result of TUNEL staining experiment using a low-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention. FIG. 12( d ) is a result of TUNEL staining experiment using a high-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention.

14 is a graph comparing the TUNEL ablation area and muscle contraction when the pulses of FIGS. 11 (a) to (d) are used.

14A shows a case in which a low-frequency monophase pulse using a monopolar electrode is applied (Group1), a case in which a low-frequency biphase pulse is applied using a bipolar electrode of the present invention (Group2), and a case using the bipolar electrode of the present invention. The experimental results of the TUNEL ablation region in the case of applying the low voltage high frequency biphase pulse (Group3) and the case of applying the high voltage high frequency biphase pulse using the bipolar electrode of the present invention (Group4) are shown. It can be seen that the TUNEL ablation area is larger in the case of using the high voltage high frequency biphase pulse using the bipolar electrode (Group4) than in the case of using the low voltage high frequency biphase pulse using the bipolar electrode of the present invention (Group3).

14(b) shows a case of applying a low-frequency monophase pulse using a monopolar electrode (Group1), a case of applying a low-frequency biphase pulse using a bipolar electrode of the present invention (Group2), and a case using the bipolar electrode of the present invention. It is a graph comparing muscle contraction when a low-voltage high-frequency bi-phase pulse is applied (Group 3) and when a high-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention is applied (Group 4). It can be seen that the muscle contraction in the case of applying the high voltage high frequency biphase pulse using the bipolar electrode of the present invention (Group4) is smaller than that in the case of applying the low frequency monophase pulse using the monopolar electrode (Group1).

15 is a graph comparing hepatocyte necrosis and apoptotic cells when the pulses of FIGS. 11 (a) to (d) are used.

15A shows a case of applying a low-frequency monophase pulse using a monopolar electrode (Group1), a case of applying a low-frequency biphase pulse using a bipolar electrode of the present invention (Group2), and a case using the bipolar electrode of the present invention. It is a graph comparing hepatocyte necrosis in the case of applying a low-voltage high-frequency bi-phase pulse (Group 3) and when applying a high-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention (Group 4). In the case of applying a low voltage high frequency biphase pulse using the bipolar electrode of the present invention (Group3), hepatocyte necrosis was small, whereas in the case of applying a high voltage high frequency biphase pulse using the bipolar electrode of the present invention (Group4), the hepatocyte necrosis was relatively It can be seen that high

15 (b) shows a case of applying a low-frequency monophase pulse using a monopolar electrode (Group1), a case of applying a low-frequency biphase pulse using a bipolar electrode of the present invention (Group2), and a case using the bipolar electrode of the present invention. It is a graph comparing apoptotic cells in the case of applying a low-voltage high-frequency bi-phase pulse (Group 3) and when applying a high-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention (Group 4). It can be seen that apoptotic cells are high in the case of applying a high-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention (Group4).

16 is a result of an experiment of immunohistochemistry (IHC) HMGB-1 when the pulses of FIGS. 11 (a) to (d) are used.

Figure 16 (a) is the result of the experiment of immunohistochemistry HMGB-1 with a monophase pulse using a low-frequency monopolar electrode. Figure 16 (b) is the result of the experiment of immunohistochemistry HMGB-1 with a low-frequency bi-phase pulse using the bipolar electrode of the present invention. Figure 16 (c) is a result of the immunohistochemistry HMGB-1 experiment using the low-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention. Figure 16 (d) is the result of the experiment of immunohistochemistry HMGB-1 using a high-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention.

FIG. 17 is a result of an immunohistochemistry (IHC) IL-6 experiment using the pulses of FIGS. 11 (a) to (d).

Figure 17 (a) is a result of the immunohistochemical IL-6 experiment using a monophasic pulse using a low-frequency monopolar electrode. Figure 17 (b) is the result of the immunohistochemical IL-6 experiment using the low-frequency bi-phase pulse using the bipolar electrode of the present invention. Figure 17 (c) is the result of the immunohistochemical IL-6 experiment using the low-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention. Figure 17 (d) is the result of the immunohistochemical IL-6 experiment using the high voltage high frequency biphase pulse using the bipolar electrode of the present invention.

18 is a graph comparing the results of immunohistochemistry (IHC) HMGB-1 and IL-6 when the pulses of FIGS. 11 (a) to (d) are used.

18A shows a case of applying a low-frequency monophase pulse using a monopolar electrode (Group1), a case of applying a low-frequency biphase pulse using a bipolar electrode of the present invention (Group2), and a case using the bipolar electrode of the present invention. It is a graph comparing immunohistochemistry HMGB-1 when a low-voltage high-frequency bi-phase pulse is applied (Group 3) and when a high-voltage high-frequency bi-phase pulse is applied using the bipolar electrode of the present invention (Group 4). It can be seen that the case of applying a low-frequency monophase pulse using a monopolar electrode (Group1) exhibits the highest HMGB-1 response compared to other groups.

18 (b) shows a case of applying a low-frequency monophase pulse using a monopolar electrode (Group1), a case of applying a low-frequency biphase pulse using a bipolar electrode of the present invention (Group2), and a case using the bipolar electrode of the present invention It is a graph comparing the immunohistochemistry IL-6 in the case of applying a low-voltage high-frequency bi-phase pulse (Group 3), and when applying a high-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention (Group 4). It can be seen that the case of applying a low-voltage high-frequency bi-phase pulse using the bipolar electrode of the present invention (Group3) exhibits the highest IL-6 response compared to other groups.

Although the present invention has been described as described above, it will be readily understood by those skilled in the art to which the present invention pertains that various modifications and variations are possible without departing from the spirit and scope of the appended claims.

10, 13. Body
20, 30, 23, 33. Electrodes
110, 120, 130, 140. Bipolar electrode
100, 200. Bipolar electrode unit for electroporation
121, 141. Straight body part
123, 143. Oblique body part
201, 203, 301, 303, 231, 233, 331, 333. switch
300. Connector
400. Control unit
401, 403. Bridge Line
500. Voltage generating unit
600. Relay switch
700. Power unit
800, 810. Bridge Circuit
801, 803, 805, 807. Earthing switch
1000. Electroporation device
D: the separation distance of the electrodes
L: electrode length
T. tumor cells

Claims (18)

A bipolar electrode unit for electroporation for the treatment of prostate cancer, comprising:
The bipolar electrode unit includes a first bipolar electrode and a second bipolar electrode,
The first bipolar electrode,
a first body elongated;
a first electrode formed on the surface of the first body; and
A second electrode spaced apart from the first electrode in the longitudinal direction of the first body and formed on the surface of the first body
including,
The second bipolar electrode,
a second body that is elongated;
a third electrode formed on the surface of the second body; and
A fourth electrode spaced apart from the third electrode in the longitudinal direction of the second body and formed on the surface of the second body
including,
A positive voltage pulse or a negative voltage pulse is applied to one or more pairs of electrodes selected from the group consisting of the first electrode, the second electrode, the third electrode, and the fourth electrode, respectively, to the one or more pairs of electrodes applied to form a bipolar electric field network,
The positive voltage pulse or the negative voltage pulse includes group pulses, respectively, the voltage of the positive voltage pulse or the negative voltage pulse is 700V to 3000V, the pulse of the positive voltage pulse or the negative voltage pulse the width is 100 μs to 1000 μs, the pulse delay of the positive voltage pulse or the negative voltage pulse is 100 μs to 2000 μs, the number of pulses of the positive voltage pulse or the negative voltage pulse is 1 to 20, the The number of group pulses is 1 to 5, and the delay of the group pulses is 100 μs to 2000 μs. A bipolar electrode unit for electroporation. In claim 1,
The first body is
an elongated straight body portion, and
The oblique body part connected while forming an angle with the straight body part
including,
The second body,
another elongated straight body portion, and
Another oblique body part connected at an angle to the other straight body part and gradually increasing the distance from the diagonal body part toward the prostate cancer.
A bipolar electrode unit for electroporation comprising a. In claim 1,
The separation distance between the first electrode and the second electrode or the separation distance between the third electrode and the fourth electrode is 4mm to 10mm for an electroporation bipolar electrode unit. In claim 1,
At least one electrode selected from the group consisting of the first electrode, the second electrode, the third electrode, and the fourth electrode has a length of 2 mm to 6 mm. A bipolar electrode unit for electroporation. A bipolar electrode unit for electroporation comprising a first bipolar electrode including a first electrode and a second electrode, and a second bipolar electrode including a third electrode and a fourth electrode;
power unit,
a voltage generating unit receiving power from the power supply unit to generate a voltage; and
A control unit controlling to apply the voltage to the first electrode, the second electrode, the third electrode, and the fourth electrode
including,
The control unit includes a first switch, a second switch, a third switch, a fourth switch, and a bridge circuit including a bridge line,
The first switch and the second switch are electrically connected in series, the third switch and the fourth switch are electrically connected in series,
The first switch and the second switch are electrically connected to each other in parallel with the third switch and the fourth switch,
The bridge line electrically connects between the first switch and the second switch and between the third switch and the fourth switch,
the control unit controls the first switch, the second switch, the third switch and the fourth switch to provide a positive voltage pulse or a negative voltage pulse to the electroporation bipolar electrode unit;
The positive voltage pulse or the negative voltage pulse includes group pulses, respectively, the voltage of the positive voltage pulse or the negative voltage pulse is 700V to 3000V, the pulse of the positive voltage pulse or the negative voltage pulse the width is 100 μs to 1000 μs, the pulse delay of the positive voltage pulse or the negative voltage pulse is 100 μs to 2000 μs, the number of pulses of the positive voltage pulse or the negative voltage pulse is 1 to 20, the The number of group pulses is 1 to 5, and the delay of the group pulses is 100 μs to 2000 μs. In claim 5,
The control unit is
a first grounding switch provided between the first switch and the second switch, and
a second grounding switch provided between the third switch and the fourth switch
Electroporation device further comprising a. delete In claim 6,
The control unit is
a fifth switch corresponding to the first switch;
a sixth switch corresponding to the second switch;
a seventh switch corresponding to the third switch;
an eighth switch corresponding to the fourth switch;
Another bridge line corresponding to the bridge line,
a third grounding switch provided between the fifth switch and the sixth switch, and
a fourth grounding switch provided between the seventh switch and the eighth switch
Further comprising another bridge circuit comprising a,
wherein the another bridge circuit is electrically connected to the bridge circuit. A first switch and a second switch connected in series, a third switch and a fourth switch connected in series, a bridge line electrically connecting between the first switch and the second switch and between the third switch and the fourth switch , Control method of a bipolar electrode unit for electroporation using a bridge circuit including a first ground switch connected between the first switch and the second switch, and a second ground switch connected between the third switch and the fourth switch As,
A first step of applying a positive voltage pulse by turning on the first switch and the fourth switch, and turning off the second switch and the third switch;
A second step of turning off the first switch, the second switch, the third switch, and the fourth switch, respectively, and turning on the second ground switch;
A third step of applying a negative voltage pulse by turning off the second ground switch, turning on the second switch and the third switch, and turning off the first switch and the fourth switch, and
A fourth step of turning off the first switch, the second switch, the third switch, and the fourth switch, respectively, and turning on the first ground switch
including,
The first step or the third step is a control method of a bipolar electrode unit for electroporation made for 0.5 μs to 2 μs. In claim 9,
The second step is a method of controlling a bipolar electrode unit for electroporation made for 2 μs to 7 μs. In claim 9,
Bipolar for electroporation further comprising a fifth step of repeating the first to fourth steps to form an electric field between the first electrode and the second electrode to which the positive voltage pulse or the negative voltage pulse is applied A method of controlling an electrode unit. In claim 9,
Step 1 to Step 4
The method of controlling a bipolar electrode unit for electroporation further comprising a fifth step of repeating for the second bipolar electrode unit. A first switch and a second switch connected in series, a third switch and a fourth switch connected in series, a bridge line electrically connecting between the first switch and the second switch and between the third switch and the fourth switch , a bridge circuit including a first ground switch connected between the first switch and the second switch, and a second ground switch connected between the third switch and the fourth switch, and
A fifth switch and a sixth switch connected in series, a seventh switch and an eighth switch connected in series, another electrically connecting between the fifth switch and the sixth switch and between the seventh switch and the eighth switch Bipolar electrode for electroporation using another bridge circuit including a bridge line, a third ground switch connected between the fifth switch and the sixth switch, and a fourth ground switch connected between the seventh switch and the eighth switch A method of controlling a unit, comprising:
A first step of applying a positive voltage pulse by turning on the first switch and the sixth switch, and turning off all the other switches;
a second step of turning off the first switch and the sixth switch and turning on the third ground switch;
A third step of applying a negative voltage pulse by turning off the third ground switch and turning on the fifth switch and the second switch, and
A fourth step of turning off the fifth switch and the second switch and turning on the first ground switch
A control method of a bipolar electrode unit for electroporation comprising a. 14. The method of claim 13,
A fifth step of applying a positive voltage pulse by turning off the first ground switch and turning on the third switch and the eighth switch;
A sixth step of turning off the third switch and the eighth switch and turning on the fourth ground switch;
A seventh step of turning off the fourth ground switch and turning on the seventh switch and the fourth switch to apply a negative voltage pulse, and
An eighth step of turning off the seventh switch and the fourth switch and turning on the second ground switch
Control method of the bipolar electrode unit for electroporation further comprising a. 15. In claim 14,
The positive voltage pulse generated in the first step or the fifth step or the negative voltage pulse generated in the third step or the seventh step is applied to the first electrode, the second electrode, the third electrode and the fourth electrode. The method of controlling a bipolar electrode unit for electroporation further comprising a ninth step that is selectively applied and is formed in a bipolar network electric field between the first electrode and the third electrode and between the second electrode and the fourth electrode. A first switch and a second switch connected in series, a third switch and a fourth switch connected in series, a bridge line electrically connecting between the first switch and the second switch and between the third switch and the fourth switch , a bridge circuit including a first ground switch connected between the first switch and the second switch, and a second ground switch connected between the third switch and the fourth switch, and
A fifth switch and a sixth switch connected in series, a seventh switch and an eighth switch connected in series, another electrically connecting between the fifth switch and the sixth switch and between the seventh switch and the eighth switch Bipolar electrode for electroporation using another bridge circuit including a bridge line, a third ground switch connected between the fifth switch and the sixth switch, and a fourth ground switch connected between the seventh switch and the eighth switch A method of controlling a unit, comprising:
A first step of applying a positive voltage pulse by turning on the fifth switch and the fourth switch, and turning off all other switches;
a second step of turning off the fifth switch and the fourth switch and turning on the second ground switch;
A third step of applying a negative voltage pulse by turning off the second ground switch and turning on the third switch and the sixth switch, and
A fourth step of turning off the first switch and the eighth switch and turning on the third ground switch
A control method of a bipolar electrode unit for electroporation comprising a. 17. The method of claim 16,
A fifth step of applying a positive voltage pulse by turning off the third ground switch and turning on the first switch and the eighth switch;
A sixth step of turning off the first switch and the eighth switch and turning on the fourth ground switch;
A seventh step of applying a negative voltage pulse by turning off the fourth ground switch and turning on the seventh switch and the second switch, and
An eighth step of turning off the seventh switch and the second switch and turning on the first ground switch
Control method of the bipolar electrode unit for electroporation further comprising a. In claim 17,
The positive voltage pulse generated in the first step or the fifth step or the negative voltage pulse generated in the third step or the seventh step is applied to the first electrode, the second electrode, the third electrode and the fourth electrode. The method of controlling a bipolar electrode unit for electroporation further comprising a ninth step that is selectively applied and is formed in a bipolar network electric field between the first electrode and the fourth electrode and between the second electrode and the third electrode.

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