CN110115803A - A kind of power supply device can be used for biomedical research and auxiliary electrode Array Design - Google Patents

A kind of power supply device can be used for biomedical research and auxiliary electrode Array Design Download PDF

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Publication number
CN110115803A
CN110115803A CN201810153359.0A CN201810153359A CN110115803A CN 110115803 A CN110115803 A CN 110115803A CN 201810153359 A CN201810153359 A CN 201810153359A CN 110115803 A CN110115803 A CN 110115803A
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power supply
supply device
electric field
frequency
voltage
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张建义
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Hebei Puni Medical Technology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/0404Electrodes for external use
    • A61N1/0408Use-related aspects
    • A61N1/0452Specially adapted for transcutaneous muscle stimulation [TMS]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/0404Electrodes for external use
    • A61N1/0408Use-related aspects
    • A61N1/0456Specially adapted for transcutaneous electrical nerve stimulation [TENS]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/0404Electrodes for external use
    • A61N1/0472Structure-related aspects
    • A61N1/0476Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Electrotherapy Devices (AREA)

Abstract

The present invention relates to a kind of power supply device that can be used for biomedical research and auxiliary electrode Array Designs.Designed power supply device can export effective voltage and the adjustable ac voltage signal of frequency.The matched electrod-array connecting with power supply device can block alternating current to apply electric fields to cell or organism by dielectric capacitance piece.By selecting suitable frequency and electric field, the effect for inhibiting target cell growth can be effectively realized.

Description

A kind of power supply device can be used for biomedical research and auxiliary electrode Array Design
Technical field
The present invention relates to the power supply devices and auxiliary electrode Array Design of the growth of selective depression specific cells.It is specifically related to Under the specific frequency for different target cell, power supply device and auxiliary electrode battle array that field strength inhibits target cell growth are improved Column.
Background technique
Based on electric field to the biological effect of cell and living tissue, living cells is for the reaction of the alternating electric field applied With frequency dependence.In low frequency (below 1 kHz), alternating electric field can be stimulated by making membrane depolarization nerve and Muscle.In addition, low frequency or impulse electric field can be with accelerating union of bone fracture.Under high frequency condition (frequency higher than 10 megahertzs), Alternating electric field can cause tissue to generate heat, this can be used for tumour ablation [document 1,2,3].
It recently include that electro photoluminescence exists since current existing cancer therapy includes the lasting limitation of chemotherapy or radiotherapy Interior new form of therapy has caused the extensive research and probe of people or clinical application interest.Medium frequency electric field for a long time by Think there is no significant impact to bioprocess, it is low strong because their alternating cannot cause very much effective neuromuscular stimulation fastly Degree can only also cause limited heating effect.However research and clinical discovery in recent years, when electric field frequency is in 100-500 thousand When in the range of hertz, applied alternating field has apparent inhibition to the speed of growth of different cancer cells in vitro and in vivo It acts on [document 1,2,3,4].It is this kind of to study the development for having subsequently resulted in the new electric field therapy of therapeutic field of tumor.Particular technique Medical research and clinical treatment for brain tumor and other cancers are had been used in some countries.[document 5,6,7,8,9]
There is specific result of study to show, applies low-intensity, the alternating electric field of intermediate frequency can press down by destroying mitosis The merisis of active tumour cell processed.In addition, finite element simulation calculation is also it has been proved that apply electric field, can to influence tumour thin The division and growth of born of the same parents.[document 2,3,4]
Under the conditions of AC field, different electric dipoles can be rotated since the alternating in alternating electric field direction changes.It is general Logical cell compares with tumour cell, since their internal different topochemistry compositions correspond to different electric dipoles, they With different dielectric responses.For example ordinary cells are different from the chemical bond details of the DNA chain of tumour cell, it means that two The DNA chain of kind cell can correspond to different dielectric responses.There is experimental evidence to show that the alternating electric field under specific frequency can To lead to the DNA key rupture failure of inside tumor cells, and then lead to death of neoplastic cells, but the electric field applied is for general The DNA chain of logical cell does not influence significantly, nor affects on the growth of normal cell.[document 1,3,4,5,6,7]
Although there are many orders that can inhibit in vitro and in vivo growth of cancer cells under the electric field action of specific frequency The inspirer experimental result of people, and had been approved by food and drug administration (FDA) and can use NovoCure The tumour of company administers electric field equipment clinical treatment brain tumor, but still for the accurate therapy mechanism to electric field treatment at present It is not clear enough.In order to more efficiently detect and treat tumour, and scientist and doctor's deep structure research is helped to understand that electric field is controlled The precise mechanism for inhibiting tumour growth is treated, while avoiding or minimizing and applying electric field unfavorable shadow possible for internal normal cell It rings, many countries, including Singapore's [document 1], Australian [document 1], the U.S. [document 1,6,7,9], France [document 2], Czech [document 2] Israel [document 2,3,4] Switzerland's [document 2,5,8], Denmark's [document 11], Hong Kong [document 10], German [document 11] is inside all in the accurate therapy mechanism for promptly studying electric field treatment tumour.
In order to which the country can study the accurate therapy mechanism of electric field treatment tumour, curative effect is improved.Possible side effect is reduced, It is necessary to design suitable power supply device and auxiliary electrode device to apply AC field, for use in there is urgent need at present Biomedical research.
The present invention can be used for biology provided with one kind in view of tumour cell is for the intensity of electric field and the dependence of frequency Medical research, alternating current is blocked, frequency and the adjustable ac power supply apparatus of voltage and auxiliary electrode array are applied.It can With the growth of the inhibition target cell for selectivity, promote to carry out biomedical research and clinical treatment using AC field. Experiment close proof, inhibits the best electric field treatment frequency of tumour growth and the size of different tumour cells inversely.Separately Outer alternating electric field is also closely related [document 2,4,7] with electric field strength to the optimal inhibition effect of different cancer cells.One in experiment Denier finds the suitable frequency for target tumor, and the life for inhibiting target cell is realized using dielectric response caused by electric field It is long, so that it may to achieve the purpose that treat tumour.
Summary of the invention
Specifically as shown in Figure 1, power supply device includes rechargeable battery, signal generator, voltage amplifier and voltage output are certainly Dynamic switching device composition.The output switching port of power supply device has 4.As shown in Fig. 2, voltage output is successively from switching port 1,2,3, 4 mouthfuls are connected to electrod-array.There are two jacks to draw two conducting wires for each delivery outlet, constitutes a circuit.
If only needing two delivery outlets to be sequentially output voltage, as shown in Figure 3, it is only necessary to connect 1-4 mouthfuls with a pair of electrodes It connects;Then 2-3 mouthfuls are connect with another pair of electrode.If only needing to need from a delivery outlet output voltage by 1-2-3-4 Mouth is connect with a pair of electrodes.
Biomedical with clinical application, if directly applying electric field to human body using metal electrode, electric current is being conducted Under the action of, the electrification mineral ion in human body cell will appear migration, lead to the variation of intracellular ion concentration, this is for people Body is harmful [document 2].Can be directly related with the life security of human body additionally, due to high conduction electric current, it is applied using metal electrode Added electric field carries out medical research and treatment, voltage can not be excessively high, and it is limited to apply voltage.Due to it is purely capacitive for conduction electric current be exhausted Edge, be conducting for AC field, so in the clinical experiment for applying alternating voltage, if utilizing the high dielectric of insulation The capacitance material of constant applies alternating voltage as electrode, so that it may avoid side effect of the conduction electric current to cell.Pass through capacitor The electric field that electrode is applied to human body is regional area, and only regional area leads to by electric field action, and without conduction electric current Cross the human region of added electric field.
In addition, not all cell growth is along single direction in cell experiment.However electric field is arrow There is amount directionality to need to improve the functioning efficiency of electric field in all directions in two (as shown in Figure 3) or multiple sides To the electric field (as shown in Figure 2) for applying same frequency.
Due to organism be ellipse or it is irregular, need when necessary using flexible dielectric make electrode, it is ensured that With well contacting for human body different parts.
Since organism is ellipse or irregular, a unitary electrode is needed using multi-disc when necessary as shown in Figure 4 The potsherd of high dielectric constant makes electrode according to different arrays, it is ensured that contacts with organism or the good of human body different parts.
Based on use above background, it is suitable to need to make using the dielectric ceramic or flexible dielectric of high dielectric constant Capacitance electrode array, to meet blocking electric current, in the effect of different directions conducting electric field.
For the understanding of the present invention, it is based on above-mentioned design, specific tumors cell can be prevented to grow.
Detailed description of the invention
It is described in detail referring to made by the following drawings to made by non-limiting example by reading, other spies of the invention Sign, objects and advantages will become more apparent upon:
Fig. 1 show power supply device.Power supply device includes four components interconnected: charge power supply, waveform signal hair Raw device, voltage amplifier, voltage output switching port.The delivery outlet of power supply device has 4, is sequentially output by 1,2,3,4 delivery outlet The voltage of same frequency.There are two jacks and external circuit to constitute a circuit for each delivery outlet.
Apply the electric field in 4 directions to the line graph of an organism surface using power supply device shown in Fig. 2.Electric field along The successively intermittent application of 4 directions.The delivery outlet of power supply device has 4, is sequentially output voltage by 1,2,3,4 delivery outlet.Biology The number that body marks position is electrode position.4 delivery outlets of electrod-array and the power supply device of 4 pairs of electrodes composition successively phase Even.There are two jacks for each port, and each pair of electrode is allowed to form a circuit.
Fig. 3 show the line graph for applying the voltage in 2 directions using power supply device.Power supply device passes through 2 delivery outlets It is connect with the electrode slice on cell liquid side.Two pairs of electrodes are added to cell liquid along X and Y-direction.The delivery outlet of power supply device has 4 A, there are two jacks for each port, and each pair of electrode is allowed to form a circuit.Voltage is sequentially output by 1,2,3,4 delivery outlet, by In 1-4,2-3 mouthfuls of connections.Output voltage is successively exchanged along X and Y-direction and is applied on cell liquid.
Fig. 4 show the Ceramic Array formed using multi-disc ceramics.It is noted, that in the Y direction, between potsherd Away from greater than ceramic diameter.Spacing between X-direction, potsherd is suitable with potsherd radius.
Fig. 5 show the schematic diagram of a 6 orifice plates.Unless stated otherwise, 4 ceramics, composition two are installed in each hole edge To electrode (as shown in Figure 6), wherein electric field is not added in 1,2,3 hole conducting wires.4,5,6 hole conducting wires connect electric field.Comparison plus with it is not powered Influence of the field to experimental result.Comparative experiments effect.Electrode scheme of installation such as Fig. 6
Fig. 6 is shown in a 6 orifice plates, and 4 ceramics are installed in hole edge, forms two pairs of electrodes.Contact conductor and power supply The port of device connects.Apply voltage from both direction.4 high dielectric ceramics are installed and constitute 2 pairs of electricity in the side in one of hole Pole.
Fig. 7 is shown using power supply device provided by the invention and electrod-array, for the experiment of Tumor cells (F98) As a result.
Fig. 8 is shown using power supply device provided by the invention and electrod-array, for the reality of lung carcinoma cell (H1299) Test result.
The same or similar appended drawing reference represents the same or similar component in attached drawing.
Specific embodiment
Selection one is used for six orifice plates (Fig. 5) of cell culture.For each hole, side is emptied, and each hole installs 4 absolutely Edge high-dielectric-constant ceramics are electrode slice (Fig. 6).The potsherd that two panels is parallel to each other can partner capacitance electrode, Mei Dui electricity At a distance of about 2 centimetres between two potsherds of pole.The connection of the output port of two pairs of orthogonal ceramic electrodes and power supply device.
Liquid medium (lung cancer or the cancer of the brain) containing tumour cell is added to 6 holes of six orifice plates.As a comparison, wherein three The electrode of the electrode no power of a hole (1,2,3 hole), the other three hole (4,5,6 hole) is powered.Observed result after 36 hours.Circuit Shown in line and Fig. 3.The direction vertical from two successively applies electric field.Six orifice plates are placed on medical guarantor according to the fostering requirement of cell In incubator.
For the two-direction sine wave voltage that Tumor cells (F98 cell) applies, the electric field side of switching in every 1.1 ± 0.2 seconds To.The preferred voltage that applies is 25 volts, and optimized frequency is 198 ± 3 kHz.Cellular change is detected after every 36 hours.Knot Fruit is as shown in Figure 7.
Apply two-direction sine wave voltage for lung carcinoma cell (non-small cell lung cancer, H1299), switches within every 1.1 ± 0.2 seconds Direction of an electric field.The preferred voltage that applies is 30 volts, and preferred frequency is 151 ± 2 kHz.It is detected after every 36 hours Cellular change.As a result as shown in Figure 8.
Experimental result characterizes T=(R1-R2)/R1 by calculating treatment enhancing proportionality coefficient T.Wherein R1 and R2 difference The growth rate of specific tumors cell when for electric field is not added or applies electric field.Obviously as T=0, without therapeutic effect.Once T > 0 indicates that the growth rate of specific cells after extra show is slack-off, treats effective.If T > 1, tumour is thin after indicating that extra show Born of the same parents' sum is reduced, and negative growth, therapeutic effect highly significant is presented.
Two kinds of cells have corresponding optimal treatment frequency, but all unified suitable high electric field of display can be mentioned obviously High inhibitory effect.
In biomedical research and clinical trial, according to the figure of animal for research and patient's human body different parts Form, as shown in Fig. 2, can apply 4 pairs of electrodes, each pair of electrode is sequentially output voltage.Effect can be more obvious.
In biomedical research and clinical trial, according to the figure of animal for research and patient's human body different parts Form, single electrode electrode can be made of a piece of potsherd with high dielectric constant.It can also be by two panels, three pieces, even Nine, 12 or 16 potsherd compositions.Every ceramics have high dielectric constant (relative dielectric constant is greater than 8000).Fig. 4 is aobvious It is shown as the single electrode with 12 potsherds.There are gap between potsherd, at least gap on one side is slightly larger than maximum potsherd Diameter.
There is thermistor behind each potsherd for the single electrode connecting with power supply device, once potsherd temperature liter Height is more than particular value, and power supply device blocks output, triggering alarm immediately.Temperature raising may be that electrode heat dissipation is bad or in height Fatigue breakdown generates heat under voltage.
In clinical trial, the electric field applied using capacitance electrode can be studied not by adjusting electric field strength and frequency The influence that same electric field intensity and frequency grow specific target cells in human body.
Power supply device provided by the invention and electrod-array are that biomedical research and clinical application are realized and inhibit tumour raw With positive effect.And it is provided by the invention preparation method is simple, suit large area to popularize use, before having good application Scape.
In addition, application range of the invention is not limited to the technique, mechanism, system of specific embodiment described in specification It makes, method and step.From the disclosure, as those skilled in the art it will be understood that for current Technique that is existing or will developing later, mechanism, manufacture, material composition, means, method or step, wherein they hold It is that the function or acquisition that the capable corresponding embodiment described with the present invention is substantially the same are substantially the same as a result, can be with according to the present invention They are applied.Therefore, appended claims of the present invention are intended to these techniques, mechanism, manufacture, means, method or step Suddenly it is included in its protection scope.

Claims (23)

1. a kind of power supply device and auxiliary electrode Array Design of the growth of selective depression specific cells.Wherein power supply device can be with Output voltage and the adjustable AC signal of frequency.Electrode is made of insulation capacitance material, and alternating current can be hindered by still Electric field is connected.
2. the output voltage of power supply device is continuously adjustable, range is 0 to 65 volts.The output waveform of power supply device can be sine Wave, triangular wave, square wave.
3. the output signal of power supply device is sequentially output by 4 ports (port numbers 1,2,3,4), the voltage in 4 directions is provided.Often The output time of a port is 0.1 second to 10 seconds (time is adjustable).
4. there are two interface, each ports to constitute an electric current by two interfaces and return for each output port of power supply device Road.
5. the output signal of power supply device can be sequentially output by two ports, the voltage of both direction is provided.
6. the output signal of power supply device can continuously be exported by a port, the voltage in a direction is provided.
7. the internal electric source of power supply device has rechargeable battery powered.
8. the reference frequency output of power supply device is 0 hertz to 1 megahertz.
9. the single electrode connecting with power supply device can be made of flexible dielectric.
10. the single electrode connecting with power supply device can be made of the single ceramic piece with high dielectric constant.
11. the single electrode connecting with power supply device can also be by the potsherd parallel connection group with high dielectric constant in varying numbers At.
12. can be furnished with thermistor behind each dielectric piece for the single electrode connecting with power supply device, once disk temperature Increasing is more than particular value (particular value can according to require parameter value adjustable), and power supply device blocks output immediately, while with alarm Prompt.
13. the single electrode connecting with power supply device can be by two panels, three pieces or even nine, 12 or 16 diameters are identical, tool It is made of the potsherd of high dielectric constant.There are gap between potsherd, gap is slightly larger than the diameter of potsherd.
14. if the electrode that a pair is parallel to each other can continuously apply alternating voltage from a direction be used for cell experiment.
15. if two pairs of orthogonal electrodes can successively apply alternating voltage from both direction be used for cell experiment.
16. if the electrode that a pair is parallel to each other can continuously apply alternating voltage from a direction be used for zoopery.
17. if two pairs of orthogonal electrodes can successively apply alternating voltage from both direction be used for zoopery.
18. if the electrode that a pair is parallel to each other can continuously apply alternating voltage from a direction be used for human clinical trial.
19. if two pairs of orthogonal electrodes can successively apply alternating voltage from both direction be used for human clinical trial.
20. if the electrode that four pairs of mutual angles are 45 degree can successively apply friendship from four direction be used for human clinical trial Galvanic electricity pressure.
21. if the electric field applied using electrod-array can be ground be used for cell experiment by adjusting electric field strength and frequency Study carefully the influence that different electric field strengths and frequency grow specific cells.
22. if the electric field applied using electrod-array can be ground be used for zoopery by adjusting electric field strength and frequency Study carefully the influence that different electric field strengths and frequency grow specific cells.
23. if the electric field applied using electrod-array can be by adjusting electric field strength and frequency be used for human clinical trial Rate studies the influence that different electric field strengths and frequency grow specific cells in human body.
CN201810153359.0A 2018-02-07 2018-02-07 A kind of power supply device can be used for biomedical research and auxiliary electrode Array Design Pending CN110115803A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111481823A (en) * 2020-05-07 2020-08-04 河北普尼医疗科技有限公司 Device for treating multiple organ tumors based on electric field

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CN106823145A (en) * 2017-03-24 2017-06-13 长沙普特斯科技有限公司 A kind of device of use amplitude modulation electric field treatment tumour
CN107281635A (en) * 2017-07-26 2017-10-24 黄勇 Electrode physical therapy device and electrode position method
WO2021136971A1 (en) * 2019-12-31 2021-07-08 Novocure Gmbh Methods, systems, and apparatuses for fast approximation of electric field distribution

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1976738A (en) * 2004-04-23 2007-06-06 诺沃库勒有限公司 Treating a tumor or the like with an electric field
CN101115522A (en) * 2004-12-07 2008-01-30 斯坦顿有限公司 Electrodes for applying an electric field in-vivo over an extended period of time
CN101626804A (en) * 2006-12-19 2010-01-13 伊西康公司 Electrode patch and method for neurostimulation
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CN106794354A (en) * 2014-07-25 2017-05-31 诚为本创新有限责任公司 For the apparatus and method of the multiple tumor by electric field treatment metastatic disease patient
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WO2021136971A1 (en) * 2019-12-31 2021-07-08 Novocure Gmbh Methods, systems, and apparatuses for fast approximation of electric field distribution

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* Cited by examiner, † Cited by third party
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CN111481823A (en) * 2020-05-07 2020-08-04 河北普尼医疗科技有限公司 Device for treating multiple organ tumors based on electric field

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