KR101788301B1 - Electroporation device and control method thereof - Google Patents

Abstract

The present invention relates to an electroporation apparatus and a control method thereof, and more particularly, to an electroporation apparatus and a control method thereof, which are capable of controlling penetration parts including a plurality of electrodes penetrated into a living body and a voltage applied to each of the plurality of electrodes, And applying a pulse with the other electrodes being opposite in polarity.

Description

ELECTROPORATION DEVICE AND CONTROL METHOD THEREOF

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an electroporation apparatus and a control method thereof, and more particularly, to an electroporation apparatus and a control method thereof that transfer an introducing agent into a tissue or a cell using an electric pulse.

Electroporation is a technique belonging to the field of molecular biology. It is a technique for introducing chemicals, drugs, and DNA into cells by increasing the permeability of the cell membrane by applying an electric field to the cells.

Such electroporation can be utilized for iontophoresis, lipid delivery, gene delivery, DNA vaccination, and the like. That is, when a short, intense electric pulse is applied to a cell, a hydrophilic pore is generated in the lipid bilayer of the cell, so that a charged molecule or a large molecule such as DNA can move into the cell .

Meanwhile, the background art of the present invention is disclosed in Korean Patent Laid-Open Publication No. 10-2014-0048213 (Apr. 24, 2014).

Such electroporation can occur by applying a relatively strong electric field, and particularly because the gap between the threshold strength of a pulse that can generate a hydrophilic pathway and the intensity of a pulse that can be destroyed by the cell is narrow, , It is necessary to use pulses of as low a strength as possible within a range that can generate a hydrophilic path for safety.

That is, in this case, a hydrophilic path can be generated only near the line connecting the anode and the cathode of the electric perforation apparatus, and a hydrophilic path is not generated in a region distant from the line by a certain distance because the electric field is less than the threshold.

However, the conventional electric perforating apparatuses generally have a pair of positive and negative electrodes to apply a fixed electric field. Therefore, there is a problem that a region where a hydrophilic path is generated is limited.

In order to solve such a problem, a multi-electrode system having a plurality of pairs of anodes and cathodes is mainly used. However, since there is a possibility of interference between a plurality of electrodes, there is a limit in accumulating electrodes in the same area. There is a problem that it is difficult to improve the drug delivery capability without increasing the amount of the drug.

SUMMARY OF THE INVENTION It is an object of the present invention to solve the problems of the conventional electric perforation apparatus and to provide an electric punching apparatus and a control method thereof capable of improving drug delivery capability without increasing the number of electrodes.

According to the present invention, there is provided an electric punching apparatus comprising: a penetrating part including a plurality of electrodes penetrating into a living body; And a controller for controlling a voltage applied to each of the plurality of electrodes and applying a pulse with one of the plurality of electrodes having a reference polarity and the other electrodes having an opposite polarity.

In the present invention, if the electrode having the reference polarity is an anode, the electrodes having the opposite polarity are cathodes, and if the electrode having the reference polarity is a cathode, the electrodes having the opposite polarity are anodes.

In the present invention, the plurality of electrodes are arranged such that the relative distance between the electrodes is the same regardless of the reference electrode.

In the present invention, the plurality of electrodes are arranged in a rectangular shape.

In the present invention, the infiltration portion may further include an injection needle for injecting the introducing agent.

In the present invention, the plurality of electrodes are in the form of needles capable of injecting the introducing agent.

In the present invention, the introduction agent is a DNA vaccine.

In the present invention, the plurality of electrodes are characterized as being intradermal, intramuscular or intratumoral.

In the present invention, the control unit sequentially changes the electrode having the reference polarity.

In the present invention, the control unit changes the electrode having the reference polarity clockwise or counterclockwise.

In the present invention, the control unit changes an electrode that becomes a reference polarity after passing through a pausing unit that does not apply a pulse.

In the present invention, the controller may apply a pulse as many times as the number of the remaining electrodes, and apply pulses using different ones of the remaining electrodes for each pulse.

In the present invention, the control unit sequentially changes the electrode to which the pulse is applied among the remaining electrodes clockwise or counterclockwise.

In the present invention, the controller may have an interval at which no pulse is applied between the pulses.

A control method of an electric perforation apparatus according to the present invention includes a first step of applying a pulse with a control electrode having one of a plurality of electrodes as a reference polarity and the other electrodes as an opposite polarity; A second step of applying a pulse with one of the electrodes having the opposite polarity in the first step as the reference polarity and the other electrodes as the opposite polarity in the first step; And a third step of causing the control unit to apply one of the electrodes having the opposite polarity in the first step and the second step to the reference polarity while applying the other polarity to the opposite polarity.

The control method of an electric perforation apparatus according to the present invention further comprises a step of stopping the control unit not applying a pulse for a rest time after the first step and the second step, And before the third step, the control unit is stopped without applying the pulse for the dormancy time.

In the present invention, the first step may include: (S1) the controller applying a pulse through one of the remaining electrodes and the electrode having the reference polarity; And a step (S2) of applying a pulse through one of the electrodes not used in the step (S1) and the electrode having the reference polarity among the remaining electrodes among the remaining electrodes.

The control method of an electroporation apparatus according to the present invention may further comprise the steps of: intradermally intramuscularly or intratumorally infiltrating a plurality of electrodes and an injection needle before the first step; And injecting the introducing agent through the plurality of electrodes and the injection needle by the control unit.

In the electroporation apparatus and the control method thereof, a pulse is applied with one of the plurality of electrodes having a reference polarity and the other electrodes having an opposite polarity, sequentially changing the electrode having a reference polarity, By using another electrode, there is an effect of improving the introduction agent transfer ability of the electric perforation apparatus.

1 is a block diagram illustrating a configuration of an electric punching apparatus according to an embodiment of the present invention.
FIG. 2A is an exemplary view illustrating a penetrating part of an electric punching apparatus according to an embodiment of the present invention.
FIG. 2B is another exemplary view for explaining a penetration part of an electric punching apparatus according to an embodiment of the present invention.
FIG. 3 is an exemplary view for explaining a pulse applying method of an electric punching apparatus according to an embodiment of the present invention.
4 is a diagram illustrating another embodiment of a pulse applying method of an electric punching apparatus according to an embodiment of the present invention.
5 is an exemplary diagram for explaining a control method of an electric punching apparatus according to an embodiment of the present invention.
6 is an exemplary diagram for explaining a pulse applying method of a control method of an electric punching apparatus according to an embodiment of the present invention.
FIG. 7 is a diagram illustrating another embodiment of a pulse applying method in a method of controlling an electric punching apparatus according to an embodiment of the present invention. Referring to FIG.

Hereinafter, an embodiment of an electric punching apparatus and a control method thereof according to the present invention will be described with reference to the accompanying drawings. In this process, the thicknesses of the lines and the sizes of the components shown in the drawings may be exaggerated for clarity and convenience of explanation. In addition, the terms described below are defined in consideration of the functions of the present invention, which may vary depending on the intention or custom of the user, the operator. Therefore, definitions of these terms should be made based on the contents throughout this specification.

FIG. 1 is a block diagram illustrating a configuration of an electric punching apparatus according to an embodiment of the present invention. FIG. 2A is a view illustrating an infiltrating unit of an electric punching apparatus according to an embodiment of the present invention, FIG. 3 is an exemplary view for explaining a pulse applying method of an electric punching apparatus according to an embodiment of the present invention, and FIG. 3 is a view for explaining a pulse applying method of an electric punching apparatus according to an embodiment of the present invention. 4 is a diagram illustrating another embodiment of a pulse applying method of an electric punching apparatus according to an embodiment of the present invention. Referring to FIG. 4, an electric punching apparatus according to an embodiment of the present invention will now be described.

As shown in FIG. 1, an electric punching apparatus according to an embodiment of the present invention includes a control unit 100 and a penetration unit 110. The penetration portion 110 may include a first electrode 111 to an n-th electrode 118 and an injection needle 119.

The electrodes 111, 112, 113, 114 and 118 of the penetration section 110 and the injection needle 119 can be infiltrated into the living body under the control of the control section 100. For example, the electrodes 111, 112, 113, 114 and 118 and the injection needle 119 are intradermal in accordance with skin suction by a suction assembly (not shown), driven under the control of the controller 100, And may be intramuscularly infiltrated and intratumoral infiltrated with movement by a motor assembly (not shown).

The injection needle 119 can inject the introduction agent into the living body under the control of the control unit 100. [ For example, the injection needle 119 may be in the form of a conventional injection needle. That is, the electric punching apparatus according to the present embodiment may include a syringe (not shown) that receives the introducing agent to inject the introducing agent into the living body.

Also, as shown in FIGS. 2A and 2B, it is preferable that the injection needle 119 is provided in a plurality of positions and is located in a region connecting the electrodes 111, 112, 113, and 114. As described above, since a hydrophilic pore is likely to be generated at a position closer to an electrode, the presence of an inducing agent in the corresponding region can smoothly transfer into the cell.

Herein, the term "inducer" refers to an agent that is delivered to a target tissue or cell through electroporation. Such an introduction agent may be a substance that can be introduced into a tissue or a cell and exhibit an activity or a function : Drugs, DNA vaccines, cosmetics).

The electrodes 111, 112, 113, 114, and 118 may be electrically pulsed in the infiltrated living body under the control of the controller 100 to allow the introduction of the introduction agent into the target tissue or cell.

The polarities of the electrodes 111, 112, 113, 114, and 118 may not be fixed. That is, the controller 100 can control the voltages applied to the electrodes 111, 112, 113, 114, and 118, respectively, so that the polarity of each electrode can be set to either the anode or the cathode.

The electrodes 111, 112, 113, 114, and 118 may also be configured to be capable of injecting an introducing agent, such as an injection needle 119. For example, the electrodes 111, 112, 113, 114, 118 may also be in the form of a common needle, such as an injection needle 119. As described above, since the introduction of the introducing agent through the electrodes 111, 112, 113, 114, and 118 is more likely to occur into the cell as the introducing agent is located around the electrode, . Therefore, according to another embodiment of the present invention, the infiltration part 110 may not have a separate injection needle 119.

On the other hand, the penetration portion 110 may be in a form detachable from the electric punching apparatus according to the present embodiment. That is, the infiltration part 110 penetrates into the living body and can be designed in the form of disposable consumables to prevent infection.

The control unit 100 may apply a pulse with one of the plurality of electrodes 111, 112, 113, 114, and 118 as a reference polarity and the other electrodes as an opposite polarity. That is, if the electrode having the reference polarity is a positive electrode, the electrodes having the opposite polarity become the negative electrode, and if the reference polarity electrode is the negative electrode, the electrodes having the opposite polarity become the positive electrode.

In other words, the control unit 100 may perform the electroporation by setting the plurality of electrodes to one anode and the remaining cathodes, or perform the electroporation by setting one cathode and the other anode. When only one reference electrode is used, the electric field can be formed in one direction. Therefore, the possibility of interference between the electric fields can be reduced compared with the case of using a plurality of anodes and a plurality of cathodes.

In the following description, it is assumed that the electrode having the reference polarity is the anode, and the electrode having the reference polarity is the cathode. In addition, although there is no limitation on the number of electrodes in the present invention, a case where four electrodes 111, 112, 113 and 114 are provided will be described as an example for convenience.

That is, the controller 100 may set the first electrode 111 as the anode, the second electrode 112, the third electrode 113, and the fourth electrode 114 as cathodes, The first electrode 111, the second electrode 112, and the fourth electrode 114 may be set as cathodes to perform electroporation only by setting the third electrode 113 as an anode.

In addition, the controller 100 may sequentially perform the electroporation by changing the electrode having the reference polarity. 3, the controller 100 sets the first electrode 111 as an anode and sets the second electrode 112, the third electrode 113, and the fourth electrode 114 as cathodes The second electrode 112 is set as an anode and the first electrode 111, the third electrode 113 and the fourth electrode 114 are set as cathodes It is possible to apply a pulse to another set. That is, the control unit 100 may perform the electroporation in such a manner that these sets are performed while changing the electrode of the reference polarity.

At this time, as shown in FIG. 3, the control unit 100 may sequentially change the electrodes having the reference polarity in the counterclockwise direction, or may sequentially change the electrodes in the clockwise direction.

In addition, when one set is terminated, the controller 100 may perform a next set after passing through a pauser not to apply a pulse. That is, when an electric field is constantly applied to a cell, cell death due to a temperature rise or the like may occur. Therefore, the control unit 100 may have a rest period in which no pulse is applied between each set for safety. Also, in general, such a rest period can be designed longer than each set time. For example, the time at which one set is performed is 30 ms and the rest period can be designed at 100 ms.

As described above, when the electrode having the reference polarity is changed, a plurality of lines connecting the positive electrode and the negative electrode can be formed, so that a hydrophilic path can be generated in a wider area. Thus, this approach can improve the ability of the electroporation apparatus to transfer the introduction agent. In addition, even if a relatively low electric field is applied (even if each line-specific region where the hydrophilic path can be formed is narrowed), the entire region in which the hydrophilic path can be generated can be maintained at the same level as that of the conventional method Enabling safe electrical penetration.

In order to apply an electric field having the same intensity regardless of the position of the electrode, a voltage proportional to the distance between the anode and the cathode must be applied to the pair of electrodes. That is, if the distance relationship between the anode and the cathode changes each time the position of the anode is rotated, an electric field of the same intensity can be formed by applying a voltage of a different value to each set. In this case, the user may feel uncomfortable, and the configuration of the circuit for controlling the voltage applied to each electrode may become complicated. Therefore, in the present embodiment, the plurality of electrodes can be arranged such that the relative distance between the electrodes is the same regardless of the reference electrode.

That is, the relative distance between the electrodes is the same regardless of the reference electrode, which means that the distances to the other electrodes are the same when each electrode is referred to. For example, when the electrodes 111, 112, 113, and 114 are arranged in a rectangular shape as shown in FIG. 3, the types of distances to the other electrodes with respect to the first electrode 111 are There are three types: horizontal, vertical, and diagonal. Even with the second electrode 112 as a reference, there are only three kinds of distances to the other electrodes: horizontal, vertical, and diagonal. That is, when the electrodes 111, 112, 113, and 114 are arranged in a rectangular shape, the controller 100 can maintain the overall electric field strength at the same level using only voltages corresponding to three kinds of distances.

On the other hand, when performing one set, the controller 100 applies pulses as many times as the number of the remaining electrodes set to the opposite polarity, and applies pulses using different ones of the remaining electrodes for each pulse. In other words, the electrode shown by a dotted line in FIG. 4 denotes an electrode to which a pulse is not applied. As shown in FIG. 4, in performing the first set, the controller 100 can apply three pulses, A pulse is applied through the electrode 111 and the second electrode 112 and then a pulse is applied through the first electrode 111 and the third electrode 113. After that, Lt; RTI ID = 0.0 > 114 < / RTI >

At this time, as shown in FIG. 4, the controller 100 may sequentially change the electrodes to which the pulses are applied in the counterclockwise direction, or may sequentially change the electrodes in the clockwise direction.

Further, the control unit 100 may have an interval in which no pulse is applied between the respective pulses. That is, as the pulse is closer to the DC form, it may damage the cell. Therefore, the controller 100 may apply one pulse for safety and then apply the next pulse through the interval. At this time, the interval of this interval may be close to the time (for example, 10 m) during which one pulse is applied rather than the scale of the pause (pause time).

If only one cathode is used when one pulse is applied, the influence due to the interference between the cathodes can be reduced, making it possible to arrange the electrodes in a narrower area.

FIG. 5 is a view for explaining a control method of an electric punching apparatus according to an embodiment of the present invention, and FIG. 6 is a view for explaining a pulse applying method of a control method for an electric punching apparatus according to an embodiment of the present invention. FIG. 7 is a view for explaining a pulse application method of the control method of an electric punching apparatus according to an embodiment of the present invention. Referring to FIG. 7, the control method of the electric punching apparatus according to the present embodiment The following is an explanation.

5, the controller 100 first penetrates the electrodes 111, 112, 113, and 114 and the injection needle 119 into the intradermally, intramuscularly, or the tumor (S500). For example, the control unit 100 can intradermally penetrate the electrodes 111, 112, 113, 114 and the injection needle 119 through skin suction by a suction assembly (not shown) The electrodes 111, 112, 113 and 114 and the injection needle 119 can be intramuscularly intratumorally intratumorally penetrated through the movement of the electrodes 111, 112, 113 and 114.

Then, the control unit 100 injects the introducing agent through the electrodes 111, 112, 113, and 114 and the injection needle 119 (S510). That is, the electrodes 111, 112, 113, and 114 may be in the form of needles capable of injecting an introducing agent, such as an injection needle 119. Here, the introduction agent refers to an agent that is delivered to a target tissue or cell through electroporation. Such an introduction agent may be a drug, a DNA vaccine, or the like.

After the step S510, the controller 100 applies a pulse through the electrodes 111, 112, 113 and 114 to introduce the introducing agent into tissues or cells (S520). That is, the controller 100 may apply a pulse through the electrodes 111, 112, 113, and 114 to perform the electroporation. The step S520 will be described in more detail with reference to FIG.

As shown in FIG. 6, the controller 100 applies a pulse with the first electrode 111 as an anode and the remaining electrodes 112, 113, and 114 as cathodes (S600). That is, the control unit 100 sets one of the electrodes 111, 112, 113, and 114 (the first electrode 111) to the reference polarity and sets the remaining electrodes 112, 113, . The step S600 will be described in more detail with reference to FIG.

As shown in FIG. 7, the controller 100 applies a pulse through the first electrode 111 and the second electrode 112 (S700). That is, the control unit 100 determines whether one of the electrodes 112, 113, 114 (the second electrode 112) set to the opposite polarity in the step S600 of FIG. 6 and the reference polarity A pulse can be applied through an electrode (first electrode 111)

Then, the controller 100 applies a pulse through the first electrode 111 and the third electrode 113 (S710). That is, the controller 100 determines whether one of the electrodes 113 and 114 (the third electrode 113) which is not used in the step S700 among the electrodes set to the opposite polarity in the step S600 of FIG. 6, The pulse may be applied through the electrode set to the reference polarity in the step S600 of FIG.

After the step S710, the controller 100 applies a pulse through the first electrode 111 and the fourth electrode 114 (S720). That is, the controller 100 may perform the step S600 of FIG. 6 by applying pulses as many times as the number of electrodes set to the cathode, and sequentially changing the electrodes to which the pulses are applied in the counterclockwise direction.

In addition, the controller 100 may have an interval at which no pulse is applied between the step S700 and the step S710 and between the step S710 and the step S720.

On the other hand, after the step S600 of FIG. 6, the control unit 100 has a rest period (S610). That is, when an electric field is constantly applied to a cell, cell death due to a temperature rise or the like may occur. Therefore, the control unit 100 may have a rest period in which no pulse is applied between each set for safety.

Next, the controller 100 applies the pulse with the second electrode 112 as the anode and the remaining electrodes 111, 113, and 114 as the cathode (S620). That is, the controller 100 sets one of the electrodes 112, 113 and 114 (the second electrode 112) having the opposite polarity in the step S600 as the reference polarity and the remaining electrodes 111, 113 and 114 It is possible to apply the pulse with the opposite polarity.

After the step S620, the control unit 100 has a pausing period (S630), applies a pulse with the third electrode 113 as an anode and the remaining electrodes 111, 112 and 114 as a cathode (S640) . That is, the controller 100 sets one of the electrodes 113 and 114 (the third electrode 113) having the opposite polarity to the reference polarity in both the step S600 and the step S620, 112, and 114 may be set to the opposite polarity to apply a pulse.

Then, the control unit 100 again has a pausing unit (S650), applying the pulse with the fourth electrode 114 as the anode and the remaining electrodes 111, 112, and 113 as the cathode (S660). That is, the control unit 100 may perform the electric puncturing in such a manner that the electrode having the reference polarity is sequentially changed, and the process of the electric puncturing can be terminated when all the electrodes perform the role of the reference polarity once.

As described above, the electric perforating apparatus and the control method thereof according to the embodiment of the present invention are configured to apply a pulse with one of the plurality of electrodes having a reference polarity and the other electrodes having an opposite polarity, sequentially changing electrodes having a reference polarity, By using different electrodes for each pulse, it is possible to reduce the possibility of interference between the electrodes, to widen the region in which the hydrophilic path is generated, and thus to improve the ability of the electroporation apparatus to transfer the introduction agent.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. I will understand. Accordingly, the technical scope of the present invention should be defined by the following claims.

100:
110:
111: first electrode
112: second electrode
113: third electrode
114: fourth electrode
118: n-th electrode
119: injection needle

Claims (18)

An electroporation apparatus for delivering an introducing agent into tissue or cells by applying an electric pulse through an electrode,
A penetration part including a plurality of electrodes penetrating into a living body; And
And a controller for controlling a voltage applied to each of the plurality of electrodes and applying a pulse with one of the plurality of electrodes having a reference polarity and the other electrodes having an opposite polarity,
The control unit applies a pulse as many times as the number of the remaining electrodes as a set and applies pulses by using different ones of the remaining electrodes for each pulse of one set Characterized in that the electrical punching device
The method according to claim 1,
Wherein when the electrode having the reference polarity is a positive electrode, the electrodes having the opposite polarity are cathodes, and if the reference electrode is a negative electrode, the electrodes having the opposite polarity are positive electrodes.
The method according to claim 1,
Wherein the plurality of electrodes are arranged such that the relative distance between the electrodes is the same regardless of the reference electrode.
The method of claim 3,
Wherein the plurality of electrodes are arranged in a rectangular shape.
The method according to claim 1,
Wherein the penetrating section further comprises an injection needle for injecting the introducing agent.
The method according to claim 1,
Wherein the plurality of electrodes are in the form of needles capable of injecting the introducing agent.
The method according to claim 1,
Wherein the introduction agent is a DNA vaccine.
The method according to claim 1,
Wherein said plurality of electrodes are intradermally, intramuscularly or intratumorally infiltrated.
The method according to claim 1,
Wherein the control unit sequentially changes the electrode having the reference polarity.
10. The method of claim 9,
Wherein the control unit changes the electrode having the reference polarity clockwise or counterclockwise.
10. The method of claim 9,
Wherein the control unit changes an electrode that becomes a reference polarity after passing through a pause period in which no pulse is applied.
delete The method according to claim 1,
Wherein the controller sequentially changes an electrode to which a pulse is applied among the remaining electrodes in a clockwise or counterclockwise direction.
The method according to claim 1,
Wherein the control unit has an interval that does not apply a pulse between each of the pulses.
A control method for an electric punching apparatus having a plurality of electrodes for applying an electric pulse,
A first step of causing the control unit to apply a pulse with one of the plurality of electrodes having a reference polarity and the other electrodes having an opposite polarity;
A second step of applying a pulse with one of the electrodes having the opposite polarity in the first step as the reference polarity and the other electrodes as the opposite polarity in the first step; And
And a third step of causing the control unit to apply a pulse with one of the electrodes having the opposite polarity in the first step and the second step with the reference polarity and the other electrodes with the opposite polarity,
In the first step,
The control unit applying a pulse through one of the remaining electrodes and the reference electrode; And
(S2) applying a pulse through one of the electrodes not used in the step (S1) and the electrode of the reference polarity among the remaining electrodes among the remaining electrodes.
16. The method of claim 15,
After the first step and before the second step,
Further comprising the step of stopping the control unit without applying a pulse for a rest time,
After the second step and before the third step,
Further comprising the step of stopping the control unit without applying a pulse for the dormant time.
delete delete

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