WO2024093734A1 - 电场能量聚焦的发射装置及方法 - Google Patents

电场能量聚焦的发射装置及方法 Download PDF

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Publication number
WO2024093734A1
WO2024093734A1 PCT/CN2023/126221 CN2023126221W WO2024093734A1 WO 2024093734 A1 WO2024093734 A1 WO 2024093734A1 CN 2023126221 W CN2023126221 W CN 2023126221W WO 2024093734 A1 WO2024093734 A1 WO 2024093734A1
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Prior art keywords
electric field
electrode
target cell
target
cell
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PCT/CN2023/126221
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English (en)
French (fr)
Inventor
尤富生
宣和均
金星
侯键
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赛福凯尔(绍兴)医疗科技有限公司
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Publication of WO2024093734A1 publication Critical patent/WO2024093734A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals

Definitions

  • the present application relates to the field of medical technology, and in particular to an electric field energy focusing emission device and method.
  • Tumor Treating Fields has become a new measure for tumor treatment. Its basic principle is to inhibit or destroy the mitosis of tumor cells by applying an electric field on tumor cells, thereby promoting their apoptosis and necrosis, and preventing their proliferation and invasion of normal cells in other tissues.
  • a transmitting device and method for electric field energy focusing are provided.
  • the present application provides a transmitting device for electric field energy focusing.
  • the device comprises an acquisition module, a processing module and a transmitting module connected in sequence, wherein:
  • the acquisition module is used to acquire the target cell position and target cell parameters, wherein the target cell parameters include at least one of cell shape, cell size, and cell direction;
  • the processing module is used to determine an electric field emission scheme based on the target cell position and the target cell parameters, wherein the electric field emission scheme includes the number of electrodes, the size of electrodes, the position of electrodes, the electric field strength of each electrode, and the excitation time;
  • the transmitting module is used to excite the target electrode based on the electric field emission scheme to generate an electric field acting on the target cell, and the target electrode is attached to the surface of the target object based on the electrode position.
  • the acquisition module is used to determine the target cell location and the target cell parameters based on pathological examination results and/or imaging examination results.
  • the processing module is further used to determine the electric field emission scheme based on a preset central electric field strength, the target cell position and the target cell parameters, and the central electric field strength is the electric field strength at the center of the target cell.
  • the processing module is also used to determine the number and size of electrodes based on the cell shape and the cell size, determine the electrode position based on the cell direction and the cell position, and determine the electric field strength and excitation time of each electrode based on the preset central electric field strength.
  • the transmitting module is further used to control the target electrodes to simultaneously excite the electric field within a preset period based on the electric field transmitting scheme.
  • the transmitting module is further used to control the target electrode to excite the electric field in a time-sharing manner within a preset period based on the electric field emission scheme.
  • the total electric field strength of the electric field strengths of the electrodes acting on the target cells is not less than a preset central electric field strength.
  • the processing module is further used to determine the excitation time difference of each electrode based on the cell position, the cell size and the shape of the part of the target object where the target cell is located.
  • the target electrodes are connected in series, in parallel, or in a combination of series and parallel.
  • the present application also provides a method for transmitting electric field energy focusing, the method comprising:
  • the target cell parameters include at least one of a cell shape, a cell size, and a cell direction;
  • the electric field emission scheme including the number of electrodes, electrode size, electrode position, electric field strength of each electrode, and excitation time;
  • the target electrode is excited based on the electric field emission scheme to generate an electric field acting on the target cell, and the target electrode is attached to the surface of the target object based on the electrode position.
  • FIG1 is a schematic diagram showing the distribution of an alternating electric field in a resting, undivided cell.
  • FIG. 2 is a schematic diagram showing the distribution of an alternating electric field in mitotic cells.
  • FIG. 3 is a curve diagram showing the relationship between applied field strength and the percentage of viable cells.
  • FIG4 is a histogram showing the relationship between the electric field direction and the number of cells.
  • FIG5 is a histogram showing the relationship between cell division period, electric field direction and cell number.
  • FIG. 6 is a schematic diagram of an electrode arrangement method for electric field therapy of tumors in the related art.
  • FIG. 7 is a structural block diagram of an electric field energy focusing transmitting device in one embodiment.
  • FIG. 8 is a schematic diagram of the number of electrodes and the positions of electrodes in one embodiment.
  • FIG. 9 is a schematic diagram of the field strength and excitation time applied by each electrode to the target cell in one embodiment.
  • FIG. 10 is a schematic diagram of the field strength and excitation time applied by each electrode to the target cell in another embodiment.
  • FIG. 11 is a schematic diagram of the field strength and excitation time difference applied by each electrode to the target cell in another embodiment.
  • FIG. 12 is a schematic diagram of the field strength and parallel excitation applied by each electrode to the target cell in another embodiment.
  • FIG. 13 is a schematic diagram of a target electrode connection method in one embodiment.
  • FIG. 14 is a schematic diagram of a target electrode connection method in another embodiment.
  • the words “connected”, “connected”, “coupled” and the like involved in this application are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect.
  • the “plurality” involved in this application refers to two or more.
  • “And/or” describes the association relationship of associated objects, Indicates that there can be three kinds of relationships. For example, “A and/or B” can mean: A exists alone, A and B exist at the same time, and B exists alone. Generally, the character “/” indicates that the objects related to each other are in an “or” relationship.
  • the terms “first”, “second”, “third”, etc. involved in this application are only used to distinguish similar objects and do not represent a specific ordering of objects.
  • module means a combination of software and/or hardware that can implement a predetermined function.
  • devices described in the following embodiments are preferably implemented in hardware, the implementation of software, or a combination of software and hardware is also possible and conceivable.
  • the basic principle of tumor electric field therapy is to curb or destroy the mitosis of tumor cells by applying an electric field to tumor cells, thereby promoting their apoptosis and necrosis, and preventing their proliferation and invasion of normal cells in other tissues.
  • an electric field As shown in Figure 1, when the resting, undivided tumor cells are subjected to an alternating electric field, the dipoles or ions only produce a "vibration" effect.
  • the tumor cells undergo mitosis as shown in Figure 2 under the action of the alternating electric field, the electric field distribution in the cells is uneven, causing the dipoles or ions to move toward the oval groove of the cells, destroying the occurrence of mitosis.
  • the horizontal axis represents the effective electric field strength applied (V/cm), and the vertical axis represents the percentage of cells that survive compared with the control group (%).
  • Curve A is a mouse melanoma cell
  • curve B is a rat glioma cell
  • curve C is a human non-small cell lung cancer cell
  • curve D is a human breast cancer cell. It is not difficult to see from Figure 3 that the greater the applied electric field strength, the better the inhibitory effect on tumor cells. And when the electric field strength is greater than 1V/cm, the growth inhibitory effect on various types of tumor cells gradually emerges.
  • Figure 4 is a histogram when the angle between the direction of the electric field and the main axis of cell mitosis is 0° (parallel), 45°, and 90° (vertical).
  • the horizontal axis represents the angle between the direction of the electric field and the main axis of tumor cell mitosis (°), and the vertical axis represents the number of cells (individuals).
  • the black bars represent the number of tumor cells that died under the action of the electric field, and the white bars represent the number of surviving tumor cells.
  • the horizontal axis represents the different stages of tumor cell mitosis
  • the vertical axis represents the number of cells
  • the black bars represent the number of tumor cells that died at different stages of division under the action of the electric field
  • the white bars represent the number of tumor cells that died without division under the action of the electric field.
  • the number of tumor cells killed was significantly greater than that in other directions, especially in the middle stage of cell division, when the electric field had the best inhibitory effect on tumor cell division, and the number of damaged cells was more than 8 times that of intact, undivided cells.
  • electric field therapy for tumors usually uses large-area electrodes, as shown in Figure 6, where electrodes are set in two mutually perpendicular directions to cross-cover the tumor area for electrical signal transmission.
  • the energy in the central cross-region is greater than 1V/cm, and generally needs to reach 2V/cm, but considering that normal tissues outside tumor cells will absorb the electric field energy to a certain extent, a voltage of 50V-200V needs to be continuously injected from the body surface.
  • the related technologies that apply electrical signals from two directions only have a good therapeutic effect on tumor cells in two dimensions, and it is difficult to treat most of the spatially distributed tumor cells.
  • a large-area electrode sheet is used, and in order to meet the field strength of the central intersection area greater than 1V/cm, a voltage of 50V-200V needs to be continuously injected from the body surface, which will cause normal cells to absorb a large amount of electric field energy and cause a certain degree of damage to normal cells.
  • the electrodes will generate a lot of heat, and the large-area electrode sheet in contact with human skin makes the human body less comfortable to wear.
  • an embodiment of the present application provides an electric field energy focusing transmitting device 100.
  • the electric field energy focusing transmitting device 100 includes an acquisition module 101, a processing module 102 and a transmitting module 103 which are connected in sequence.
  • the acquisition module 101 is used to acquire the target cell position and target cell parameters, wherein the target cell parameters include at least one of cell shape, cell size, and cell direction.
  • the target cell position includes the position of the target cell in the center of the cell group in the organism, wherein the cell group is formed by multiple cells.
  • the target cell parameters include at least one of cell shape, cell size, and cell direction.
  • the target cell shape includes the shape of a single target cell, or the shape of a cell group formed by multiple cells as a whole, and the shape may include approximately circular, approximately elliptical, nodular, lobed, etc., which is not limited in the present application.
  • the target cell size includes the size of a single target cell, or the size of a cell group formed by multiple cells as a whole, and the size may include at least one of the maximum cross-sectional perimeter, the maximum cross-sectional diameter, the maximum cross-sectional radius, and the volume.
  • the cell direction of the target cell includes the main axis direction of mitosis of a single target cell, or the main axis direction of mitosis of all cells in a cell group formed by multiple cells.
  • the acquisition module 101 can determine the target cell position and target cell parameters based on at least one of the pathological examination results, imaging examination results, endoscopic examination results, radioimmunology examination results, or medical laser examination results. The present application does not specifically limit the medical detection method used by the acquisition module 101 to obtain the target cell position and target cell parameters.
  • the processing module 102 is used to determine an electric field emission scheme based on the target cell position and the target cell parameters.
  • the electric field emission scheme includes the number of electrodes, electrode size, electrode position, electric field strength of each electrode, and excitation time.
  • the electric field emission scheme is used to indicate the specific emission mode of the electrode.
  • the electrode includes an electrode device for applying an electric field to the target cell, and the electrode device may include an electrode sheet, an electrode wire or an electrode mesh, etc., which is not limited in the present application.
  • the number of electrodes is the number of electrodes set for applying an electric field, and a pair of electrode sheets usually generates an electric field in one direction.
  • the electrode size is the area or size of two electrodes that generate an electric field. In some embodiments, it can be understood that the electrode size can also be the area of the part in contact with the skin.
  • the electrode size in the embodiment of the present application can be the area of the part in contact with the skin.
  • the electrode position is the installation position of the electrode, and the electrode position determines the position and direction of the applied electric field.
  • the electric field strength of each electrode includes the preset electric field strength of each electrode, or the electric field strength applied to the target cell. It can be understood that the electric field strength can also include parameters such as voltage strength and current strength, which are not specifically limited in the present application.
  • the excitation time includes the excitation start time and end time of the target electrode. Specifically, the excitation time can include the continuous excitation time of the target electrode, the interval time between two excitations, or the excitation cycle time.
  • the electrode size can also be set to be smaller accordingly, and the number of electrodes and the electric field strength of each electrode can also be reduced accordingly, but the comprehensive field strength applied to the target cell should be greater than 1V/cm.
  • the processing module 102 determines the axis with the smallest acute angle with all spindle directions by calculation.
  • the field strength direction generated by a larger number of electrodes can be made as small as possible with the axis angle, that is, the electric field direction is set to be parallel to the axis as much as possible, so as to achieve the purpose of more effective inhibition of the division of more cells.
  • the transmitting module 103 is used to excite the target electrode based on the electric field emission scheme to generate an electric field acting on the target cell, and the target electrode is attached to the surface of the target object based on the electrode position.
  • the target object i.e., the electrode on the patient's body
  • the target object can determine the size and number of the target electrodes according to the electric field emission requirements after determining the electric field emission scheme, and attach the corresponding number of target electrodes to the corresponding positions on the patient's body; or electrodes of different sizes and numbers can be attached to various positions on the patient's body in advance, including the target electrodes and other electrodes, and when emitting the electric field, only the corresponding target electrodes are excited based on the electric field emission scheme.
  • the above method can be selected by the operator according to the needs in actual application, and is not specifically limited here.
  • the target electrode includes an electrode capable of implementing the electric field emission scheme.
  • an electric field acting on the target cell is generated based on the electric field emission scheme to inhibit the division and proliferation of the target cell.
  • the number of target electrodes is less than or equal to the number of all electrodes.
  • the target cells are a small number of cells. When a cell group of a relatively small size is formed, some electrodes can be excited based on the electric field emission scheme, and the target electrodes are the electrodes that need to be excited.
  • the acquisition module 101 acquires the target cell position and target cell parameters, and the target cell parameters include at least one of cell shape, cell size, and cell direction;
  • the processing module 102 determines the electric field emission scheme based on the target cell position and the target cell parameters, and the electric field emission scheme includes the number of electrodes, electrode size, electrode position, electric field strength of each electrode, and excitation time;
  • the emission module 103 excites the target electrode based on the electric field emission scheme to generate an electric field acting on the target cell.
  • different target cell parameters different electric field emission schemes are determined, and then the target electrode is excited according to different emission schemes so that the electric field acts on the target cell.
  • the number, size, position and electric field strength of the electrodes can be flexibly adjusted for different target cells, so that the electric field accurately acts on tumor cells without affecting normal tissues, thereby improving the tumor inhibition effect.
  • the acquisition module 101 can be used to determine the target cell location and target cell parameters based on the pathological examination results and/or imaging examination results.
  • the target cell position and target cell parameters can be determined based on the pathological examination results, or based on the imaging examination results.
  • the acquisition module 101 can also determine the target cell position and target cell parameters based on at least one of the endoscopic examination results, radioimmunological examination results, or medical laser examination results. It can be understood that in some other embodiments, the acquisition module 101 can also comprehensively determine the target cell position and target cell parameters based on any two or more of the above-mentioned multiple examination results to make the final result obtained more accurate.
  • electric field therapy for tumors usually uses two pairs of electrodes to apply an electric field.
  • the number of electrodes can be flexibly set according to different electric field emission schemes, but the number of electrodes in the emission device 100 for focusing electric field energy is not less than 4.
  • the number of electrodes can be 4 or 8.
  • the number of electrodes is set based on the electric field emission scheme.
  • the electric field strength of each electrode in the emission device 100 for focusing electric field energy can be less than the preset electric field strength.
  • the field strength applied to the target cells can reach the preset electric field strength, and at the same time, the strength of each of at least two pairs of electrodes can be less than the preset electric field strength.
  • the heat generated by each electrode can be reduced by setting the electrode field strength in a dispersed and superimposed manner, making the wearer more comfortable.
  • a small electrode sheet smaller than a standard electrode sheet is used as a target electrode to improve wearing comfort, and the electric field is applied more accurately to reduce the impact on normal cells.
  • the processing module 102 is also used to determine the electric field emission scheme based on a preset central electric field strength, the target cell position and the target cell parameters, wherein the central electric field strength is the electric field strength at the center of the target cell.
  • the electric field strength at the center of the target cell includes the electric field strength at the center of a single target cell, or the electric field strength at the center of a cell group formed by multiple cells.
  • the preset center electric field strength is the strength of the electric field that needs to be formed at the center of the target cell to achieve the expected tumor cell inhibition effect. Including the preset center electric field strength in the influencing factors for determining the electric field emission scheme so that the intensity of the electric field excited according to the electric field emission scheme at the center of the target cell is not less than the preset center electric field strength can further improve the inhibitory effect on cell division.
  • the emission scheme determined by the processing module 102 is: the number of electrodes and the electrode position are shown in Figure 8, the number of electrodes is 8 (i.e., 4 pairs of electrodes, including electrodes 1 and 5, electrodes 2 and 6, electrodes 3 and 7, electrodes 4 and 8), and the electrode position is that the electric field generated by each pair of electrodes covers the target cells.
  • the electrode size is set to a small electrode sheet attached to the surface of the human body.
  • the excitation time of each electrode is shown in Figure 9, and the excitation intensity of each electrode is 50V, and the field strength reaching the center of the target cell is 2V/cm.
  • the excitation time is that electrodes 1 and 5 continue to excite for 0.25 seconds, and other electrodes do not excite. At 0.25 seconds, electrodes 1 and 5 stop excitation while electrodes 2 and 6 continue to excite for 0.25 seconds, and other electrodes do not excite. In this way, four pairs of electrodes are excited and circulated separately in sequence.
  • the electric field emission scheme in the embodiment of the present application makes the field strength applied to the target cells consistent at any time during use, but by distributing the total electric field energy among the four pairs of electrodes, the excitation time of each electrode is divided into one-fourth of the case of excitation of a single electrode pair, so the heat generation of each electrode is reduced, which increases the comfort of the wearer.
  • the electric field applied to the target cells in each second of the excitation cycle covers all directions, effectively inhibiting the division and proliferation of each tumor cell in all directions, further improving the inhibitory effect of tumor cells.
  • the processing module 102 is also used to determine the number and size of electrodes based on the cell shape and cell size, determine the electrode position based on the cell direction and cell position, and determine the electric field strength and excitation time of each electrode based on the preset central electric field strength.
  • different electric field emission schemes can be determined based on different target cell positions and target cell parameters to achieve targeted inhibition of proliferation of different target cells.
  • the electrode size can also be set to be smaller, and the number of electrodes and the electric field strength of each electrode can also be reduced accordingly, but the comprehensive field strength applied to the target cell should be greater than 1V/cm.
  • the processing module 102 determines by calculation the axis with the smallest acute angle with all the main axis directions.
  • the electric field strength direction generated by a large number of electrodes is set to have the smallest angle with the axis, that is, the electric field direction is set to be parallel to the axis as much as possible, so as to achieve the purpose of more effectively inhibiting the division of more cells.
  • the electric field strength and excitation time of each electrode can also be determined according to the preset central electric field strength. By adjusting the electric field strength and excitation time of each electrode, the electric field emission scheme can be flexibly selected after comprehensively considering the field strength applied to the target cells and the wearing comfort.
  • the transmitting module 103 is also used to control the target electrode to simultaneously excite the electric field within a preset period based on the electric field emission scheme.
  • the control of the target electrode to simultaneously excite the electric field within a preset period based on the electric field emission scheme includes simultaneously exciting multiple target electrodes, such as 4 or 8 electrodes. Taking 4 pairs of electrodes as an example, 4 pairs of electrodes are synchronously triggered, and the electric field applied to the target cells is increased by using the principle of electric field energy superposition. However, since the electric field energy excited by each electrode is not large, it not only ensures the suppression effect, but also makes the electric field energy absorbed by normal tissues less. At the same time, the heat generation of each electrode is reduced, which improves the comfort of the wearer.
  • the electric field strength of each electrode is not greater than the preset strength. It is understandable that, due to the principle of electric field energy superposition, the electric field energy is dispersed to multiple target electrodes, so the electric field strength of each electrode can be less than the preset electric field strength.
  • the preset electric field strength is the standard electric field strength when a large-area electrode sheet is used in the related art to continuously stimulate the electric field to inhibit target cells. Generally speaking, the more target electrodes are excited at the same time, the smaller the electric field strength excited by each electrode.
  • the transmitting module 103 is also used to control the target electrode to excite the electric field in a preset period based on the electric field emission scheme.
  • the control of the target electrode to excite the electric field in a preset period based on the electric field emission scheme includes dividing the target electrode into preset electrode pairs; and sequentially and cyclically exciting the preset electrode pairs in a preset period based on the electric field emission scheme.
  • the embodiment of the present application can effectively reduce the heat generated when each electrode is excited by dispersing the total energy to multiple electrodes for separate excitation, thereby improving the wearing comfort of the human body.
  • the electric field strength of each electrode is not less than the preset strength. It is understandable that when the target electrode is controlled to excite the electric field in a preset period, each electrode is only excited for part of the time in a complete period to generate an electric field. In order to ensure that the electric field strength generated at the center of the target cell at each moment meets the requirements of inhibiting the target cell, the electric field strength excited by each electrode cannot be less than the preset electric field strength.
  • the preset electric field strength is the standard electric field strength when a large-area electrode sheet is used in the related art to continuously excite the electric field to inhibit the target cell. Generally speaking, the shorter the excitation time of each electrode, the greater the electric field strength excited by each electrode.
  • the total electric field strength of the electric field strengths of the electrodes acting on the target cells is not less than a preset central electric field strength.
  • the electric field strength at the center of the target cell includes the electric field strength at the center of a single target cell, or the electric field strength at the center of a cell group formed by multiple cells.
  • the expected tumor cell inhibition effect requires the strength of the electric field formed at the center of the target cell. It is understandable that, whether it is time-sharing excitation or simultaneous excitation, it is necessary to ensure that the intensity of the electric field excited according to the electric field emission scheme at the center of the target cell is not less than the preset central electric field intensity in order to achieve the expected inhibitory effect on cell division.
  • the electric field emission scheme determined by the processing module 102 provided in the present application is further described below through a specific embodiment.
  • the target cell is a cell group with a larger size, and the preset central electric field strength is 4V/cm.
  • the emission scheme determined by the processing module 102 is: the number of electrodes and the electrode position are shown in Figure 8, the number of electrodes is 8 (i.e., 4 pairs of electrodes, including electrode 1 and electrode 5, electrode 2 and electrode 6, electrode 3 and electrode 7, electrode 4 and electrode 8), and the electrode position is that the electric field generated by each pair of electrodes covers the target cells.
  • the electrode size is set so that each electrode is a small electrode sheet attached to the surface of the human body.
  • the excitation time of each electrode is shown in Figure 10, the excitation intensity of each electrode is 100V, and the field strength reaching the center of the target cell is 4V/cm.
  • the excitation time is that electrode 1 and electrode 5 are continuously excited for 0.125 seconds, and other electrodes are not excited. At 0.125 seconds, electrode 1 and electrode 5 stop exciting while electrode 2 and electrode 6 are continuously excited for 0.125 seconds, and other electrodes are not excited. In this way, the four pairs of electrodes are excited and cycled separately in sequence.
  • the electric field emission scheme in the embodiment of the present application makes the field strength applied to the target cells consistent at any time during the treatment process, but by distributing the total electric field energy among the four pairs of electrodes, the excitation time of each electrode is split into one-eighth of the case of excitation of a single electrode pair, so the heat generation of each electrode is further reduced, so that the wearer's comfort is increased.
  • the electric field strength applied to the target cells is 4V/cm, which can more effectively inhibit the growth of tumor cells.
  • the electric field applied to the target cells in each second of the excitation cycle covers all directions, effectively inhibiting the division and proliferation of each tumor cell in all directions, further improving the inhibitory effect of tumor cells.
  • the processing module 102 is further used to determine the excitation time difference of each electrode based on the position of the target cell, the size of the cell, and the shape of the part of the target object where the target cell is located.
  • the electrode wearing area may be an irregular shape, such as the head of a human body. Therefore, in order to ensure that the electric field energy of each electrode can overlap when it reaches the center of the target cell, the phase focusing principle can be referred to when the processing module 102 determines the electric field emission scheme. As shown in Figure 11, taking 4 pairs of electrodes (electrode 1 and electrode 5, electrode 2 and electrode 6, electrode 3 and electrode 7, electrode 4 and electrode 8) as an example, the excitation time difference ⁇ t of each electrode is determined based on the position of the target cell, the cell size and the shape of the part of the target object where the target cell is located.
  • the electric field energy efficiency generated by different electrodes on the target cell is the same by setting the excitation time difference ⁇ t, so that the electric field energy is superimposed and focused.
  • the electric field energy output by each electrode is reduced by the principle of electric field superposition, but the energy focusing superposition reaching the target cell part can achieve the suppression effect of high field strength.
  • reducing the electric field energy output by each electrode can also reduce the heat generated by each electrode, improve the comfort of the wearer, and at the same time, the energy absorbed by normal tissues and cells is also less, and the harm to normal tissues and cells is further reduced.
  • the present application embodiment also provides an electric field emission solution, and the processing module 100 is also used to
  • the target cell size and the preset central electric field coverage size determine the electric field emission scheme, and the preset central electric field coverage size is the overlapping size of the electric field and the target cell.
  • the emission scheme can be determined based on the synchronous excitation electrode and the multi-layer superposition focusing method.
  • electrode 1 and electrode 5 and electrode 5 electrode 2 and electrode 6, electrode 3 and electrode 7, electrode 4 and electrode 8
  • the preset central electric field coverage size is equal to the cell size
  • 4 pairs of electrodes are synchronously triggered, and the principle of electric field energy superposition is used to increase the electric field applied at the target cell.
  • the electric field energy excited by each electrode is not large, it not only ensures the therapeutic effect, but also makes the electric field energy absorbed by normal tissue less, and at the same time, the heat generation of each electrode is reduced, so that the wearer's comfort is improved.
  • the connection mode of the target electrodes is series connection and/or parallel connection.
  • the target electrode sheets can be connected in parallel, as shown in Figure 13, and the electric signal generator can excite different electrode sheets at different times and with different electric field energies based on different electric field emission schemes.
  • the target electrode sheets can also be connected in series, as shown in Figure 14, and the electric signal generator can control the excitation of all target electrode sheets based on the electric field emission scheme in a time-sharing manner.
  • the target electrode sheets can also be set to a mixed connection mode of parallel and series connection.
  • the embodiment of the present application also provides an electric field energy focusing emission method applied to the above-mentioned electric field energy focusing emission device 100.
  • the implementation scheme for solving the problem provided by the method is similar to the implementation scheme recorded in the above-mentioned device, so the specific limitations in the electric field energy focusing emission method provided below can refer to the limitations of the electric field energy focusing emission device 100 above, and will not be repeated here.
  • a method for transmitting electric field energy focusing comprising:
  • S101 Acquire the target cell position and target cell parameters, wherein the target cell parameters include at least one of cell shape, cell size, and cell direction.
  • S103 Determine an electric field emission scheme based on the target cell position and the target cell parameters, wherein the electric field emission scheme includes the number of electrodes, the size of electrodes, the position of electrodes, the electric field strength of each electrode, and the excitation time.
  • S105 Exciting the target electrode based on the electric field emission scheme to generate an electric field acting on the target cell.
  • Each module in the above-mentioned electric field energy focusing transmitting device can be implemented in whole or in part by software, hardware and a combination thereof.
  • the above-mentioned modules can be embedded in or independent of the processor in the computer device in the form of hardware, or can be stored in the memory in the computer device in the form of software, so that the processor can call and execute the operations corresponding to the above modules.
  • the acquisition module 101 is a memory
  • the processing module 102 is a processor
  • the transmitting module 103 is an electrical signal generator, etc.
  • user information involved in this application including but not limited to user device information, user personal information Information, etc.
  • data including but not limited to data used for analysis, stored data, displayed data, etc.
  • any reference to the memory, database or other medium used in the embodiments provided in the present application can include at least one of non-volatile and volatile memory.
  • Non-volatile memory can include read-only memory (ROM), magnetic tape, floppy disk, flash memory, optical memory, high-density embedded non-volatile memory, resistive random access memory (ReRAM), magneto resistive random access memory (MRAM), ferroelectric random access memory (FRAM), phase change memory (PCM), graphene memory, etc.
  • Volatile memory can include random access memory (RAM) or external cache memory, etc.
  • RAM can be in various forms, such as static random access memory (SRAM) or dynamic random access memory (DRAM).
  • SRAM static random access memory
  • DRAM dynamic random access memory
  • the database involved in each embodiment provided in this application may include at least one of a relational database and a non-relational database.
  • Non-relational databases may include distributed databases based on blockchain, etc., but are not limited to this.
  • the processor involved in each embodiment provided in this application may be a general-purpose processor, a central processing unit, a graphics processor, a digital signal processor, a programmable logic unit, a data processing logic unit based on quantum computing, etc., but are not limited to this.

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Abstract

一种电场能量聚焦的发射装置及方法。发射装置包括依次相连的获取模块、处理模块以及发射模块，其中：获取模块用于获取目标细胞位置及目标细胞参数，目标细胞参数包括细胞形状、细胞尺寸、细胞方向中的至少一个；处理模块用于基于目标细胞位置及目标细胞参数确定电场发射方案，电场发射方案包括电极数量、电极大小、电极位置、各电极的电场强度以及激发时间；发射模块用于基于电场发射方案激发目标电极，产生作用于目标细胞的电场。

Description

电场能量聚焦的发射装置及方法
相关申请
本申请要求2022年11月3日申请的，申请号为202211372285.2，名称为“电场能量聚焦的发射装置及方法”的中国专利申请的优先权，在此将其全文引入作为参考。
技术领域
本申请涉及医疗技术领域，特别是涉及一种电场能量聚焦的发射装置及方法。
背景技术
近年来肿瘤电场治疗(TumorTreating Fields，TTF)成为肿瘤治疗的一种新型措施，其基本原理为通过在肿瘤细胞上施加电场来抑制或破坏肿瘤细胞的有丝分裂，进而促使其凋亡和坏死，阻止其增殖和侵袭其它组织的正常细胞。
在相关的肿瘤电场治疗技术中，由于肿瘤细胞具有增殖快、位置不固定、有丝分裂方向随机的特性，因此通常是通过两对大面积电极施加垂直的大范围电场对肿瘤细胞进行治疗，以确保覆盖肿瘤细胞的区域。然而，这种方式不仅无法准确将电场施加到肿瘤细胞上，起到抑制作用，还会影响正常细胞组织，比如吸收过多电场能量而产热。
因此，在肿瘤电场治疗技术中，亟需一种能够更好地抑制肿瘤的电场能量聚焦的发射装置。
发明内容
根据本申请的各种实施例，提供一种电场能量聚焦的发射装置及方法。
第一方面，本申请提供了一种电场能量聚焦的发射装置。所述装置包括依次相连的获取模块、处理模块以及发射模块，其中：
所述获取模块用于获取目标细胞位置及目标细胞参数，所述目标细胞参数包括细胞形状、细胞尺寸、细胞方向中的至少一个；
所述处理模块用于基于所述目标细胞位置及所述目标细胞参数确定电场发射方案，所述电场发射方案包括电极数量、电极大小、电极位置、各电极的电场强度以及激发时间；
所述发射模块用于基于所述电场发射方案激发目标电极，产生作用于目标细胞的电场，所述目标电极基于所述电极位置贴附在目标对象表面。
在其中一个实施例中，所述获取模块用于基于病理检查结果和/或影像学检查结果确定所述目标细胞位置及所述目标细胞参数。
在其中一个实施例中，所述处理模块还用于基于预设中心电场强度，所述目标细胞位置以及所述目标细胞参数确定电场发射方案，所述中心电场强度为所述目标细胞中心处的电场强度。
在其中一个实施例中，所述处理模块还用于基于所述细胞形状以及所述细胞尺寸确定电极数量以及电极大小，基于所述细胞方向以及所述细胞位置确定所述电极位置，基于所述预设中心电场强度确定各电极的电场强度以及激发时间。
在其中一个实施例中，所述发射模块还用于基于所述电场发射方案控制所述目标电极在预设周期内同时激发电场。
在其中一个实施例中，所述发射模块还用于基于所述电场发射方案控制所述目标电极在预设周期内分时激发电场。
在其中一个实施例中，所述各电极的电场强度作用于所述目标细胞的总电场强度不小于预设中心电场强度。
在其中一个实施例中，所述处理模块还用于基于所述细胞位置、所述细胞尺寸以及所述目标细胞所在目标对象的部位形状确定各电极的激发时间差。
在其中一个实施例中，所述目标电极的连接方式为串联连接、并联连接或串并联组合连接。
第二方面，本申请还提供了一种电场能量聚焦的发射方法，所述方法包括：
获取目标细胞位置及目标细胞参数，所述目标细胞参数包括细胞形状、细胞尺寸、细胞方向中的至少一个；
基于所述目标细胞位置及所述目标细胞参数确定电场发射方案，所述电场发射方案包括电极数量、电极大小、电极位置、各电极的电场强度以及激发时间；
基于所述电场发射方案激发目标电极，产生作用于目标细胞的电场，所述目标电极基于所述电极位置贴附在目标对象表面。
本申请的一个或多个实施例的细节在以下附图和描述中提出，以使本申请的其他特征、目的和优点更加简明易懂。
附图说明
为了更清楚地说明本申请实施例或相关技术中的技术方案，下面将对实施例或相关技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅是本申请的 一些实施例，对于本领域普通技术人员而言，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为交变电场在静息态未分裂细胞的分布示意图。
图2为交变电场在有丝分裂细胞的分布示意图。
图3为施加场强与存活细胞百分比关系的曲线示意图。
图4为电场方向与细胞数量关系的直方图。
图5为细胞分裂时期、电场方向与细胞数量关系的直方图。
图6为相关技术中肿瘤电场治疗的电极片设置方式示意图。
图7为一个实施例中电场能量聚焦的发射装置的结构框图。
图8为一个实施例中电极数量与电极位置的示意图。
图9为一个实施例中各电极施加在目标细胞上场强与激发时间的示意图。
图10为另一个实施例中各电极施加在目标细胞上场强与激发时间的示意图。
图11为另一个实施例中各电极施加在目标细胞上场强与激发时差的示意图。
图12为另一个实施例中各电极施加在目标细胞上场强与并行激发的示意图。
图13为一个实施例中目标电极连接方式的示意图。
图14为另一个实施例中目标电极连接方式的示意图。
具体实施方式
下面将结合本申请实施例中的附图，对本申请实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
除另作定义外，本申请所涉及的技术术语或者科学术语应具有本申请所属技术领域具备一般技能的人所理解的一般含义。在本申请中的“一”、“一个”、“一种”、“该”、“这些”等类似的词并不表示数量上的限制，它们可以是单数或者复数。在本申请中所涉及的术语“包括”、“包含”、“具有”及其任何变体，其目的是涵盖不排他的包含；例如，包含一系列步骤或模块(单元)的过程、方法和系统、产品或设备并未限定于列出的步骤或模块(单元)，而可包括未列出的步骤或模块(单元)，或者可包括这些过程、方法、产品或设备固有的其他步骤或模块(单元)。在本申请中所涉及的“连接”、“相连”、“耦接”等类似的词语并不限定于物理的或机械连接，而可以包括电气连接，无论是直接连接还是间接连接。在本申请中所涉及的“多个”是指两个或两个以上。“和/或”描述关联对象的关联关系， 表示可以存在三种关系，例如，“A和/或B”可以表示：单独存在A，同时存在A和B，单独存在B这三种情况。通常情况下，字符“/”表示前后关联的对象是一种“或”的关系。在本申请中所涉及的术语“第一”、“第二”、“第三”等，只是对相似对象进行区分，并不代表针对对象的特定排序。
以下所使用的术语“模块”、“单元”等为可以实现预定功能的软件和/或硬件的组合。尽管在以下实施例中所描述的装置较佳地以硬件来实现，但是软件，或者软件和硬件的组合的实现也是可能并被构想的。
为使本申请提供的技术方案更加便于理解和应用，现对本申请涉及的相关技术进行说明。
肿瘤电场治疗的基本原理为通过在肿瘤细胞上施加电场来遏制或破坏肿瘤细胞的有丝分裂，进而促使其凋亡和坏死，阻止其增殖和侵袭其它组织的正常细胞。如图1所示，静息态未分裂的肿瘤细胞受到交变电场作用时，偶极子或离子仅产生“振动”效应。但在肿瘤细胞进行有丝分裂时，如图2所示，在交变电场的作用下，细胞内的电场分布不均匀，使得偶极子或离子向细胞卵圆沟方向移动，破坏有丝分裂的发生。所以，结合图1、图2以及上述描述可知，在肿瘤细胞进行有丝分裂时施加交变电场可以抑制其分裂过程，且当电场方向与肿瘤细胞有丝分裂主轴的方向平行时抑制效果最好。
在对肿瘤细胞施加电场时，场强越大则抑制效果越好。如图3所示，横轴表示施加的有效电场强度(V/cm)，纵轴表示与对照组相比存活的细胞百分比数(％)，曲线A为小鼠黑色素瘤细胞，曲线B为大鼠胶质瘤细胞，曲线C为人非小细胞肺癌细胞，曲线D为人乳腺癌细胞。从图3中不难看出，施加的电场强度越大，对肿瘤细胞抑制效果越好。且电场强度大于1V/cm时，对各类肿瘤细胞的生长抑制效果逐渐显现。
下面结合图4、图5说明施加电场的方向对抑制肿瘤细胞分裂的影响。图4为电场方向与细胞有丝分裂主轴方向的夹角为0°(平行)、45°、90°(垂直)时的直方图，横轴表示电场方向与肿瘤细胞有丝分裂主轴方向的夹角角度(°)，纵轴表示细胞数量(个)，黑色条柱表示在电场作用下肿瘤细胞的死亡数量，白色条柱表示存活的肿瘤细胞数量。从图4中可以看出，电场方向和细胞有丝分裂主轴方向平行时(即夹角为0°时)，破坏损伤的肿瘤细胞数量是其他方向的5倍多，表明将电场方向与细胞有丝分裂主轴方向设置为平行是最佳的治疗选择。另一方面，在肿瘤细胞有丝分裂的不同时期，对不同的电场方向也有着不同的敏感程度。如图5所示，横轴表示肿瘤细胞有丝分裂的不同时期，纵轴表示细胞数量(个)，黑色条柱表示在电场作用下不同分裂时期肿瘤细胞的死亡数量，白色条柱表示在电场作用下完整未分裂肿瘤细胞的死亡数量。从图5中可以看出，在细胞分裂的中、 后、末各个时期，电场方向和肿瘤细胞有丝分裂主轴方向平行时，杀死的肿瘤细胞数量明显多于其他方向，尤其是在细胞分裂的中期电场对肿瘤细胞分裂的抑制效果最好，破坏损伤的细胞数量是完整未分裂细胞的8倍多。
在相关技术中的肿瘤电场治疗通常利用大面积的电极片，如图6所示，从两个相互垂直的方向设置电极片，交叉覆盖肿瘤区域进行电信号传输。通常中心交叉的区域能量为大于1V/cm，一般需要达到2V/cm，但考虑到肿瘤细胞外的正常组织会对电场能量进行一定程度的吸收，所以需要从体表持续注入50V-200V的电压。
从上述相关技术中不难看出，由于肿瘤区域内部的细胞是多方向的空间分布，所以相关技术中从两个方向施加电信号仅对两个维度的肿瘤细胞有着较好的治疗效果，难以治疗大部分空间分布的肿瘤细胞。其次，为覆盖肿瘤区域的大小使用大面积的电极片，且为了满足中心相交的区域场强大于1V/cm需要从体表持续注入50V-200V的电压，会导致正常细胞吸收较大的电场能量，对正常细胞会造成一定程度的损伤。再者，为需要满足电场能量需要，电极会产生大量的热量，大面积的电极片与人体皮肤接触使人体佩戴的舒适性较差。
基于此，本申请实施例提供一种电场能量聚焦的发射装置100，如图7所示，所述电场能量聚焦的发射装置100包括依次相连的获取模块101、处理模块102以及发射模块103。
获取模块101用于获取目标细胞位置及目标细胞参数，所述目标细胞参数包括细胞形状、细胞尺寸、细胞方向中的至少一个。
本申请实施例中，所述目标细胞位置包括处于细胞群中心位置的目标细胞位于生物体内的位置，其中所述细胞群由多个细胞形成。所述目标细胞参数包括细胞形状、细胞尺寸、细胞方向中的至少一个。目标细胞形状包括单个目标细胞形状，或多个细胞形成的细胞群整体的形状，所述形状可以包括近似圆形、近似椭圆、结节状、分叶状等，本申请对此不作限制。目标细胞尺寸包括单个目标细胞尺寸，或多个细胞形成的细胞群整体的尺寸，所述尺寸可以包括最大截面周长、最大截面直径、最大截面半径、体积中的至少一个。所述目标细胞的细胞方向包括单个目标细胞有丝分裂的主轴方向，或多个细胞形成的细胞群中所有细胞有丝分裂的主轴方向。本申请实施例中，获取模块101可以基于病理检查结果、影像学检查结果、内窥镜检查结果、放射免疫学检查结果或医用激光检查结果中至少一个确定目标细胞位置及目标细胞参数。本申请对获取模块101获取目标细胞位置及目标细胞参数所采用的医学检测方式不作具体限制。
处理模块102用于基于所述目标细胞位置及所述目标细胞参数确定电场发射方案，所述电场发射方案包括电极数量、电极大小、电极位置、各电极的电场强度以及激发时间。
本申请实施例中，所述电场发射方案用于指示电极的具体发射方式。所述电极包括用于对目标细胞施加电场的电极装置，所述电极装置可以包括电极片、电极线或电极网等，本申请对此不作限制。所述电极数量为设置用于施加电场的电极数量，一对电极片通常会生成一个方向的电场。所述电极大小为生成一个电场的两个电极的面积或尺寸。在一些实施例中，可以理解的，所述电极大小也可以是与皮肤接触部分的面积，例如在电极的尺寸较大而与皮肤接触的面积较小的情况下，本申请实施例中的电极大小可以是与皮肤接触部分的面积。所述电极位置为电极的安装位置，所述电极位置决定了施加电场的位置和方向。所述各电极的电场强度包括各电极的预设电场强度，或施加在目标细胞上的电场强度。可以理解的，所述电场强度也可以包括电压强度、电流强度等参数，本申请对此不作具体限制。所述激发时间包括目标电极的激发起始时间和结束时间。具体的，所述激发时间可以包括目标电极的持续激发时间、两次激发的间隔时间或激发周期时间等。
本申请实施例中，可以理解的，基于不同的目标细胞位置及目标细胞参数，可以确定不同的电场发射方案，以实现对不同目标细胞增殖的针对性抑制。例如，在一些实施例中，当目标细胞尺寸较小时，电极大小也可以相应设置为较小，电极数量和各电极的电场强度也可相应降低，但应保证施加在目标细胞上的综合场强大于1V/cm。又例如，在其他一些实施例中，当目标细胞为多个细胞形成的细胞群时，在确定所有细胞的有丝分裂主轴方向后，处理模块102通过计算确定与所有主轴方向所夹锐角角度最小的轴线。进而可以通过设置电极位置，使较多数量的电极所生成的场强方向与所述轴线夹角尽量小，即尽可能将电场方向设置为与所述轴线平行，以达到对更多细胞的分裂进行更有效抑制的目的。
发射模块103用于基于所述电场发射方案激发目标电极，产生作用于目标细胞的电场，所述目标电极基于所述电极位置贴附在目标对象表面。
可以理解的，目标对象即患者身上的电极，可以在确定电场发射方案后根据电场发射需求确定目标电极的大小及目标电极的数量，并将对应数量的目标电极贴附在患者身上的对应位置；也可以预先在患者身上各个位置贴附不同大小和数量的电极，其中包括目标电极和其它电极，在发射电场时仅基于电场发射方案激发对应的目标电极。上述方式可以由操作者在实际应用中根据需求进行选择，此处不做具体限定。
本申请实施例中，所述目标电极包括能够实现所述电场发射方案的电极。当激发目标电极时，会基于电场发射方案产生作用于目标细胞的电场，以抑制目标细胞的分裂增殖。可以理解的，目标电极的数量小于或等于所有电极的数量。例如，在一些实施例中，针对较多数量细胞形成的细胞群施加电场时，为实现更好的抑制效果，可能基于电场发射方案激发所有电极，此时目标电极为所有电极。在另一些实施例中，目标细胞为较少数量细胞 形成的体积较小的细胞群时，基于电场发射方案激发部分电极即可，此时目标电极即为部分需要激发的电极。
本申请实施例提供的电场能量聚焦的发射装置100中，获取模块101获取目标细胞位置及目标细胞参数，所述目标细胞参数包括细胞形状、细胞尺寸、细胞方向中的至少一个；处理模块102基于所述目标细胞位置及所述目标细胞参数确定电场发射方案，所述电场发射方案包括电极数量、电极大小、电极位置、各电极的电场强度以及激发时间；发射模块103基于所述电场发射方案激发目标电极，产生作用于目标细胞的电场。根据不同的目标细胞参数，确定不同的电场发射方案，再根据不同的发射方案激发目标电极使电场作用于目标细胞，可以针对不同的目标细胞灵活调整电极的数量、大小、位置和电场强度，使电场准确作用在肿瘤细胞上，而不影响正常组织，提高了肿瘤的抑制效果。另一方面，也可以在确定电场发射方案时尽量选择与人体皮肤接触总面积较小的方案，或选择每个电极生成场强较小的方案，可以通过灵活的方案选择提高人体佩戴的舒适性。
本申请实施例中，获取模块101可以用于基于病理检查结果和/或影像学检查结果确定目标细胞位置及目标细胞参数。
本申请实施例中，可以基于病理检查结果确定目标细胞位置及目标细胞参数，也可以基于影像学检查结果确定目标细胞位置及目标细胞参数。当然，获取模块101还可以基于内窥镜检查结果、放射免疫学检查结果或医用激光检查结果中至少一个确定目标细胞位置及目标细胞参数。可以理解的，在其他的一些实施例中，获取模块101也可以基于上述多个检查结果中的任意两个或多个来综合确定目标细胞位置及目标细胞参数，以使获取的最终结果更加准确。
正如前述，在相关技术中的肿瘤电场治疗通常使用两对电极片施加电场。本申请实施例中，可以根据不同电场发射方案灵活设置电极数量，但电场能量聚焦的发射装置100中的电极数量不少于4个。在一些实施例中，电极数量可以为4个或8个。在其他一些实施例中，所述电极数量基于电场发射方案进行设置。另外，本申请实施例中，电场能量聚焦的发射装置100中各电极的电场强度可以小于预设电场强度。通过至少两对电极生成电场的叠加作用，可以使施加在目标细胞上的场强达到预设电场强度，同时可以使至少2对电极各自的强度小于预设电场强度。本申请实施例中通过上述电极数量和电极电场强度的设置，一方面可以满足施加在肿瘤细胞上的电场具有足够的电场强度，另一方面可以通过电极场强分散叠加的设置方式使每个电极产生的热量减少，使佩戴者更加舒适。
在本实施例中，采用大小小于标准电极片的小型电极片作为目标电极，以提高佩戴舒适性，并且电场施加更加精准，减小对正常细胞的影响。
为更有效地抑制目标细胞分裂以进一步提高抑制效果，本申请实施例中，处理模块102还用于基于预设中心电场强度、目标细胞位置以及目标细胞参数确定电场发射方案，所述中心电场强度为所述目标细胞中心处的电场强度。
本申请实施例中，所述目标细胞中心处的电场强度包括单个目标细胞中心处的电场强度，或多个细胞形成的细胞群中心位置的电场强度。其中，预设中心电场强度即为要达到预期的肿瘤细胞抑制效果，需要在目标细胞中心形成的电场的强度。将预设中心电场强度纳入确定电场发射方案的影响因素，使根据电场发射方案激发的电场在目标细胞中心的强度不小于预设中心电场强度，可以进一步提高对细胞分裂的抑制效果。
下面通过一个具体实施例对本申请中基于预设中心电场强度、目标细胞位置以及目标细胞参数确定电场发射方案进行说明。在本申请一个实施例中，获取模块101确定目标细胞位置及目标细胞参数后，预设中心电场强度为2V/cm的情况下，处理模块102确定的发射方案为：电极数量、电极位置如图8所示，电极数量为8(即4对电极，包括电极1与电极5、电极2与电极6、电极3与电极7、电极4与电极8)，电极位置为每对电极产生的电场均覆盖目标细胞。电极大小设置为贴敷在人体表面的小型电极片。各电极的激发时间如图9所示，各电极的激励强度为50V，到达目标细胞中心的场强为2V/cm。激发时间为电极1与电极5持续激发0.25秒，其它电极不激发。0.25秒时电极1与电极5停止激发的同时再使电极2与电极6持续激发0.25秒，其它电极不激发。以此使四对电极依次单独激发并循环。本申请实施例中的电场发射方案，使得使用过程中任何时刻施加在目标细胞上的场强均一致，但通过将总电场能量分布于4对电极中，将每个电极的激发时间拆分为单独电极对激发情况下的四分之一，所以每个电极的产热量减少，使佩戴者舒适度增加。同时每一秒的激发周期内施加在目标细胞上的电场覆盖了所有方向，有效抑制了各个肿瘤细胞的沿各个方向的分裂增殖，进一步提高了肿瘤细胞的抑制效果。
本申请实施例中，处理模块102还用于基于所述细胞形状以及细胞尺寸确定电极数量以及电极大小，基于所述细胞方向以及细胞位置确定所述电极位置，基于所述预设中心电场强度确定各电极的电场强度以及激发时间。
本申请实施例中，基于不同的目标细胞位置及目标细胞参数，可以确定不同的电场发射方案，以实现对不同目标细胞增殖的针对性抑制。例如，在一些实施例中，当目标细胞尺寸较小时，电极大小也可以相应设置为较小，电极数量和各电极的电场强度也可相应降低，但应保证施加在目标细胞上的综合场强大于1V/cm。又例如，在其他一些实施例中，当目标细胞为多个细胞形成的细胞群时，在确定所有细胞的有丝分裂主轴方向后，处理模块102通过计算确定与所有主轴方向所夹锐角角度最小的轴线。进而可以通过设置电极位 置，使较多数量的电极所生成的场强方向与所述轴线夹角尽量小，即尽可能将电场方向设置为与所述轴线平行，以达到对更多细胞的分裂进行更有效抑制的目的。在另外一些实施例中，还可以根据预设中心电场强度确定各电极的电场强度以及激发时间，通过对各电极电场强度以及激发时间的调整，可以综合考虑施加在目标细胞上场强与佩戴舒适度后灵活选择电场发射方案。
本申请实施例中，发射模块103还用于基于所述电场发射方案控制所述目标电极在预设周期内同时激发电场。所述基于所述电场发射方案控制所述目标电极在预设周期内同时激发电场包括，同时激发多个目标电极，如4个或8个电极，以4对电极为例，同步触发4对电极，利用电场能量叠加的原理，使目标细胞处施加的电场变大。但由于每个电极激发的电场能量并不大，所以既保证了抑制效果，也使得正常组织吸收的电场能量较少，同时每个电极发热量降低，使佩戴者舒适度提升。
本申请实施例中，所述各电极的电场强度不大于预设强度。可以理解的，由于利用电场能量叠加的原理，电场能量分散到了多个目标电极，因此每个电极的电场强度可以小于预设电场强度。示例性地，预设电场强度为相关技术中采用大面积的电极片，持续激发电场抑制目标细胞时的标准电场强度。一般来说，同时激发的目标电极的数量越多，每一电极激发的电场强度越小。
本申请实施例中，发射模块103还用于基于所述电场发射方案控制所述目标电极在预设周期内分时激发电场。所述基于所述电场发射方案控制所述目标电极在预设周期内分时激发电场包括，将所述目标电极划分为预设电极对；基于所述电场发射方案在预设周期内依次并循环激发所述预设电极对。本申请实施例通过将总能量分散设置于多个电极上分别激发，可以有效降低每个电极被激发时产生的热量，提高人体佩戴舒适度。
本申请实施例中，所述各电极的电场强度不小于预设强度。可以理解的，当控制所述目标电极在预设周期内分时激发电场时，每一电极仅在一个完整周期内的部分时间激发，产生电场，为保证每一时刻在目标细胞中心处产生的电场强度均满足抑制目标细胞的需求，每一电极激发的电场强度不能小于预设电场强度。示例性地，预设电场强度为相关技术中采用大面积的电极片，持续激发电场抑制目标细胞时的标准电场强度。一般来说，每一电极的激发时间越短，每一电极激发的电场强度越大。
在一个实施例中，所述各电极的电场强度作用于目标细胞的总电场强度不小于预设中心电场强度。
本申请实施例中，所述目标细胞中心处的电场强度包括单个目标细胞中心处的电场强度，或多个细胞形成的细胞群中心位置的电场强度。其中，预设中心电场强度即为要达到 预期的肿瘤细胞抑制效果，需要在目标细胞中心形成的电场的强度。可以理解的，无论是分时激发还是同时激发，均需要保证根据电场发射方案激发的电场在目标细胞中心的强度不小于预设中心电场强度，才能达到对细胞分裂的预期抑制效果。
下面通过一个具体实施例对本申请提供的处理模块102确定的电场发射方案做进一步描述。在本申请一个实施例中，获取模块101确定目标细胞位置及目标细胞参数后，确定目标细胞为尺寸较大的细胞群，预设中心电场强度为4V/cm。处理模块102确定的发射方案为：电极数量、电极位置如图8所示，电极数量为8(即4对电极，包括电极1与电极5、电极2与电极6、电极3与电极7、电极4与电极8)，电极位置为每对电极产生的电场均覆盖目标细胞。电极大小设置为每个电极均为贴敷在人体表面的小型电极片。各电极的激发时间如图10所示，各电极的激励强度为100V，到达目标细胞中心的场强为4V/cm。激发时间为电极1与电极5持续激发0.125秒，其它电极不激发。0.125秒时电极1与电极5停止激发的同时再使电极2与电极6持续激发0.125秒，其它电极不激发。以此使四对电极依次单独激发并循环。本申请实施例中的电场发射方案，使得治疗过程中任何时刻施加在目标细胞上的场强均一致，但通过将总电场能量分布于4对电极中，将每个电极的激发时间拆分为单独电极对激发情况下的八分之一，所以每个电极的产热量进一步减少，使佩戴者舒适度增加。同时施加在目标细胞上的电场强度为4V/cm，可以更加有效地抑制肿瘤细胞的生长。另外，每一秒的激发周期内施加在目标细胞上的电场覆盖了所有方向，有效抑制了各个肿瘤细胞的沿各个方向的分裂增殖，进一步提高了肿瘤细胞的抑制效果。
本申请实施例中，处理模块102还用于基于所述目标细胞位置、所述细胞尺寸以及所述目标细胞所在所述目标对象的部位形状确定各电极的激发时间差。
本申请实施例中，电极佩戴区域可能为不规则形状，如人体的头部。因此为保证每个电极到达目标细胞中心时电场能量能够重叠，在处理模块102确定电场发射方案时可以参考相位聚焦原理。如图11所示，以4对电极(电极1与电极5、电极2与电极6、电极3与电极7、电极4与电极8)为例，基于所述目标细胞位置、所述细胞尺寸以及所述目标细胞所在所述目标对象的部位形状确定各电极的激发时间差Δt。在利用电场能量叠加原理的前提下，通过设置激发时间差Δt使得不同电极在目标细胞上产生的电场能量效率相同，使电场能量叠加聚焦。本申请实施例中通过电场叠加原理，使每个电极输出的电场能量减小，但到达目标细胞部位的能量聚焦叠加可以达到高场强的抑制效果。另外，减小每个电极的输出的电场能量，也可以使每个电极产生的热量减少，佩戴者舒适度提升，同时正常组织和细胞吸收的能量也较少，对正常组织和细胞的危害性也进一步降低。
本申请实施例还提供一种电场发射方案，处理模块102还用于基于目标细胞形状、目 标细胞尺寸以及预设中心电场覆盖尺寸确定电场发射方案，所述预设中心电场覆盖尺寸为所述电场与所述目标细胞的重叠尺寸。本申请实施例中，可以理解的，所述预设中心电场覆盖尺寸越大则抑制目标细胞分裂增殖的效果越好，当所述预设中心电场覆盖尺寸等于目标细胞尺寸时抑制效果最佳。在一些实施例中，可以基于同步激发电极且利用多层叠加聚焦的方式确定发射方案。如图12所示，以4对电极(电极1与电极5、电极2与电极6、电极3与电极7、电极4与电极8)为例，满足所述预设中心电场覆盖尺寸等于细胞尺寸的情况下，同步触发4对电极，利用电场能量叠加的原理，使目标细胞处施加的电场变大。但由于每个电极激发的电场能量并不大，所以既保证了治疗效果，也使得正常组织吸收的电场能量较少，同时每个电极发热量降低，使佩戴者舒适度提升。
对于电极的连接方式，本申请实施例提供的电场能量聚焦的发射装置100中，所述目标电极的连接方式为串联连接和/并联连接。本申请实施例中目标电极片可以并联连接，如图13所示，电信号发生器可以基于不同的电场发射方案分别对不同电极片进行不同时间、不同电场能量的激发。在另一些实施例中，目标电极片也可以串联连接，如图14所示，电信号发生器可以基于电场发射方案分时控制激发所有目标电极片。当然，在其他实施例中，目标电极片也可以设置为并联、串联的混合连接方式。
基于同样的发明构思，本申请实施例还提供了一种应用于上述电场能量聚焦的发射装置100的电场能量聚焦的发射方法。该方法所提供的解决问题的实现方案与上述装置中所记载的实现方案相似，故下面所提供的电场能量聚焦的发射方法中的具体限定可以参见上文中对于电场能量聚焦的发射装置100的限定，在此不再赘述。
在一个实施例中，提供了一种电场能量聚焦的发射方法，所述方法包括：
S101：获取目标细胞位置及目标细胞参数，所述目标细胞参数包括细胞形状、细胞尺寸、细胞方向中的至少一个。
S103：基于所述目标细胞位置及所述目标细胞参数确定电场发射方案，所述电场发射方案包括电极数量、电极大小、电极位置、各电极的电场强度以及激发时间。
S105：基于所述电场发射方案激发目标电极，产生作用于目标细胞的电场。
上述电场能量聚焦的发射装置中的各个模块可全部或部分通过软件、硬件及其组合来实现。上述各模块可全部或部分以硬件形式内嵌于或独立于计算机设备中的处理器中，也可以以软件形式存储于计算机设备中的存储器中，以便于处理器调用执行以上各个模块对应的操作。如获取模块101为存储器，处理模块102为处理器，以及发射模块103为电信号发生器等。
需要说明的是，本申请所涉及的用户信息(包括但不限于用户设备信息、用户个人信 息等)和数据(包括但不限于用于分析的数据、存储的数据、展示的数据等)，均为经用户授权或者经过各方充分授权的信息和数据。
本领域普通技术人员可以理解实现上述实施例方法中的全部或部分流程，是可以通过计算机程序来指令相关的硬件来完成，所述的计算机程序可存储于一非易失性计算机可读取存储介质中，该计算机程序在执行时，可包括如上述各方法的实施例的流程。其中，本申请所提供的各实施例中所使用的对存储器、数据库或其它介质的任何引用，均可包括非易失性和易失性存储器中的至少一种。非易失性存储器可包括只读存储器(Read-Only Memory，ROM)、磁带、软盘、闪存、光存储器、高密度嵌入式非易失性存储器、阻变存储器(ReRAM)、磁变存储器(Magneto resistive RandomAccess Memory，MRAM)、铁电存储器(Ferroelectric Random Access Memory，FRAM)、相变存储器(Phase Change Memory，PCM)、石墨烯存储器等。易失性存储器可包括随机存取存储器(Random Access Memory，RAM)或外部高速缓冲存储器等。作为说明而非局限，RAM可以是多种形式，比如静态随机存取存储器(Static Random Access Memory，SRAM)或动态随机存取存储器(Dynamic Random Access Memory，DRAM)等。本申请所提供的各实施例中所涉及的数据库可包括关系型数据库和非关系型数据库中至少一种。非关系型数据库可包括基于区块链的分布式数据库等，不限于此。本申请所提供的各实施例中所涉及的处理器可为通用处理器、中央处理器、图形处理器、数字信号处理器、可编程逻辑器、基于量子计算的数据处理逻辑器等，不限于此。
以上实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本申请的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对本申请专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本申请构思的前提下，还可以做出若干变形和改进，这些都属于本申请的保护范围。因此，本申请的保护范围应以所附权利要求为准。

Claims (10)

  1. 一种电场能量聚焦的发射装置，其特征在于，包括依次相连的获取模块、处理模块以及发射模块，其中：
    所述获取模块用于确定目标细胞位置及目标细胞参数，所述目标细胞参数包括细胞形状、细胞尺寸、细胞方向中的至少一个；
    所述处理模块用于基于所述目标细胞位置及所述目标细胞参数确定电场发射方案，所述电场发射方案包括电极数量、电极大小、电极位置、各电极的电场强度以及激发时间；
    所述发射模块用于基于所述电场发射方案激发目标电极，产生作用于目标细胞的电场，所述目标电极基于所述电极位置贴附在目标对象表面。
  2. 根据权利要求1所述的电场能量聚焦的发射装置，其中，所述获取模块用于基于影像学检查结果和/或病理检查结果确定所述目标细胞位置及所述目标细胞参数。
  3. 根据权利要求1所述的电场能量聚焦的发射装置，其中，所述处理模块还用于基于预设中心电场强度、所述目标细胞位置以及所述目标细胞参数确定电场发射方案，所述中心电场强度为所述目标细胞中心处的电场强度。
  4. 根据权利要求3所述的电场能量聚焦的发射装置，其中，所述处理模块还用于基于所述细胞形状以及所述细胞尺寸确定电极数量以及电极大小，基于所述细胞方向以及所述细胞位置确定所述电极位置，基于所述预设中心电场强度确定各电极的电场强度以及激发时间。
  5. 根据权利要求1所述的电场能量聚焦的发射装置，其中，所述发射模块还用于基于所述电场发射方案控制所述目标电极在预设周期内同时激发电场。
  6. 根据权利要求1所述的电场能量聚焦的发射装置，其中，所述发射模块还用于基于所述电场发射方案控制所述目标电极在预设周期内分时激发电场。
  7. 根据权利要求5或6所述的电场能量聚焦的发射装置，其中，所述各电极的电场强度作用于所述目标细胞的总电场强度不小于预设中心电场强度。
  8. 根据权利要求1所述的电场能量聚焦的发射装置，其中，所述处理模块还用于基于所述目标细胞位置、所述细胞尺寸以及所述目标细胞所在所述目标对象的部位形状确定各电极的激发时间差。
  9. 根据权利要求1所述的电场能量聚焦的发射装置，其中，所述目标电极的连接方式为串联连接、并联连接或串并联组合连接。
  10. 一种电场能量聚焦的发射方法，其特征在于，所述方法包括：
    获取目标细胞位置及目标细胞参数，所述目标细胞参数包括细胞形状、细胞尺寸、细胞方向中的至少一个；
    基于所述目标细胞位置及所述目标细胞参数确定电场发射方案，所述电场发射方案包括电极数量、电极大小、电极位置、各电极的电场强度以及激发时间；
    基于所述电场发射方案激发目标电极，产生作用于目标细胞的电场，所述目标电极基于所述电极位置贴附在目标对象表面。
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