CN106357246A - Pulse generator for cell electroporation - Google Patents
Pulse generator for cell electroporation Download PDFInfo
- Publication number
- CN106357246A CN106357246A CN201610898167.3A CN201610898167A CN106357246A CN 106357246 A CN106357246 A CN 106357246A CN 201610898167 A CN201610898167 A CN 201610898167A CN 106357246 A CN106357246 A CN 106357246A
- Authority
- CN
- China
- Prior art keywords
- circuit
- pulse
- power amplifier
- output
- resistance
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000004520 electroporation Methods 0.000 title claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims abstract description 7
- 230000005669 field effect Effects 0.000 claims description 35
- 239000003990 capacitor Substances 0.000 claims description 15
- 230000005611 electricity Effects 0.000 claims description 12
- 229910010271 silicon carbide Inorganic materials 0.000 claims description 11
- 230000000295 complement effect Effects 0.000 claims description 10
- 230000015556 catabolic process Effects 0.000 claims description 9
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical class [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 claims description 9
- 238000002955 isolation Methods 0.000 claims description 7
- 230000008859 change Effects 0.000 claims description 5
- 101100372898 Caenorhabditis elegans vha-5 gene Proteins 0.000 claims description 3
- 101100156282 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) vib-1 gene Proteins 0.000 claims description 2
- 101100540540 Schizosaccharomyces pombe (strain 972 / ATCC 24843) big1 gene Proteins 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 14
- 230000002427 irreversible effect Effects 0.000 abstract description 9
- 238000004146 energy storage Methods 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 7
- 230000002441 reversible effect Effects 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 19
- 206010028980 Neoplasm Diseases 0.000 description 8
- 230000005684 electric field Effects 0.000 description 8
- 210000000170 cell membrane Anatomy 0.000 description 7
- 210000001367 artery Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- 210000003701 histiocyte Anatomy 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000012637 gene transfection Methods 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 235000013547 stew Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
Classifications
-
- H—ELECTRICITY
- H03—ELECTRONIC CIRCUITRY
- H03K—PULSE TECHNIQUE
- H03K7/00—Modulating pulses with a continuously-variable modulating signal
- H03K7/08—Duration or width modulation ; Duty cycle modulation
-
- H—ELECTRICITY
- H03—ELECTRONIC CIRCUITRY
- H03K—PULSE TECHNIQUE
- H03K5/00—Manipulating of pulses not covered by one of the other main groups of this subclass
- H03K5/01—Shaping pulses
Landscapes
- Physics & Mathematics (AREA)
- Nonlinear Science (AREA)
- Dc-Dc Converters (AREA)
Abstract
The invention belongs to the technical field of medical instruments and particularly relates to a pulse generator for cell electroporation. The pulse generator comprises a power conversion circuit, an energy storage circuit, a pulse output circuit, a signal controller, an electrode and a power supply, wherein the output end of the power supply is connected with the power conversion circuit; the power conversion circuit is connected with the electrode by the energy storage circuit and the pulse output circuit in sequence; the signal controller is connected with the control input end of the pulse output circuit; and by a control signal output by the signal controller, a pulse output signal of the pulse output circuit is controlled so as to enable the electrode to discharge. The pulse generator has the advantages that the output waveform of the generator is close to a square wave, so that the generation of heat in the process of electric impact is reduced, the adjustment range of pulse parameters is wide, and the application range is wide; and the impact-pulse voltage amplitude, maximum pulse current, pulse width, pulse period and pulse times can be set according to the specific requirements, so that the pulse generator can be used for in-vivo and in-vitro reversible and irreversible electroporation experiments.
Description
Technical field
The invention belongs to technical field of medical instruments is and in particular to a kind of pulse generator of cell electroporation.
Background technology
Cell electroporation refers under Electro-pulsing Field, and cell membrane produces the physical process of micropore.According to impulse electric field
The difference of intensity, pulse width and effect number of times, electroporation is divided into reversible electroporation and irreversible electroporation；Reversible electroporation is
Under conditions of the electric field that cell membrane applies suitable intensity and width, impulse electric field makes to produce temporary transient, reversible hole on cell membrane
Road or penetrating.After Electro-pulsing Field, duct natural enclosing, cell can recover normal condition, penetrating due to cell membrane
Property increase, can make under other transport mechanism, to make some macromole can pass through cell membrane.Reversible electroporation makes intraor extracellular divide
Sub- exchange capacity dramatically increases, and is conducive to cell to absorb various medicines, genetic stew, protein and other macromole etc..By electricity
Pulse is combined with chemotherapeutics treatment tumor, has founded the electric pulse chemotherapy of tumor, this method is than conventional chemotherapy effect
More preferably, and side effect is less.When impulse electric field exceedes the limit that cell can bear, after electric field, cell membrane can not seal again
Close, cell expendable rupture and leads to cell death, and this phenomenon is referred to as irreversible electrical breakdown.Whether generation can not
Inverse electroporation, relevant with the physicochemical characteristicss of the width of electric pulse, pulse amplitude, pulse number and cell.
In the electroporation applied research in past, such as gene transfection, tumor electrochemotherapy etc., using the reversibility of cell
Electric breakdown phenomena, controls irreversible electrical breakdown phenomenon, electric pulse is induced one in tumor tissues, so that malignant cell is occurred
Irreversible electrical breakdown, destroys the conditions of existence of tumor, has reached the purpose of killing tumor cell.This without change
Treat medicine, be used alone high intense pulsed electric field and can lead to tumor cell programmed death (apoptosis) and can effectively suppress the life of tumor
Long.This tumor therapeuticing method is referred to as irreversible electroporation tumour ablation art.
The waveform parameters such as the electric field intensity applied in electroporation process, frequency, pulse width, directly affect electroporation
Efficiency and result, at present, adopt Exponential Decay Wave and two kinds of square wave, Exponential Decay Wave electroporative pulses are to charge using electric capacity more
The waveform producing by histiocyte electric discharge, the energy storing in electric capacity is all bled off by this process, because capacitance voltage declines
Afterwards, its electric field intensity does not reach the threshold value of electroporation, so this portion of energy does not play electroporation effect, and is merely creating heat,
But current control is relatively simple, by contrast, square wave electroporation pulses generator is to control output waveform using electrical switch, its
Efficiency is higher, and the heat of generation is less, because various waveform parameters are larger on the efficiency impact of electroporation, needs to various parameters
It is optimized research.
Content of the invention
The purpose of the present invention is the problems referred to above and the deficiency solving prior art, the invention provides a kind of cell electroporation
Pulse generator, the present invention can make living cells produce reversibility or irreversible electrical breakdown, greatly reduce surge process
The generation of middle heat, improves the frequency of electroporative pulses, and to achieve these goals, the technical solution used in the present invention is such as
Under:
A kind of pulse generator of cell electroporation is it is characterised in that include power converting circuit, accumulator, pulse
Output circuit, signal controller, electrode and power supply, the outfan of described power supply is connected with power converting circuit, this power conversion
Circuit passes sequentially through accumulator, impulse output circuit is connected with electrode, the control of described signal controller and impulse output circuit
Input processed connects, and the control signal being exported by signal controller is thus control the pulse output signals of impulse output circuit to make
Electrode is discharged.
Preferably, described power converting circuit is a road, or for more than two-way being connected in parallel, described impulse output circuit is
One tunnel, or for more than two-way being connected in parallel, more than power converting circuit more than a road or two-way and a road or two-way
Accumulator is attached, and institute's accumulator and impulse output circuit more than a road or two-way are attached.
Preferably, described power converting circuit includes pulse-width modulation circuit, booster circuit, filter circuit and rectification circuit,
The signal output part of described pulse-width modulation circuit is connected with the control end of booster circuit, this booster circuit by filter circuit with
The input of described rectification circuit connects, and described power supply is also connected with the input of described booster circuit, filter circuit respectively, institute
The outfan stating rectification circuit is connected with accumulator.
Preferably, described pulse-width modulation circuit include pwm controller, resistance r1, resistance r2, resistance r3, adjustable resistance r4,
Resistance r5, electric capacity c1 and electric capacity c2, described booster circuit includes field effect q1, field effect q2 and booster transformer t1, described storage
Electric capacity c3 and electric capacity c4 can be included by circuit, described rectification circuit includes diode d1 and diode d2, one end of described resistance r1
It is connected with the oscillating discharge outfan of pwm controller, one end of described resistance r2 is inputted with the vibration timing resistor of pwm controller
End connects, and one end of electric capacity c1 is connected with the vibration timing capacitor input of pwm controller, the other end of described resistance r1, electricity
The other end of the resistance other end of r2 and electric capacity c1 is all connected to ground, one end of described resistance r3, one end of adjustable resistance r4, adjustable
The centre cap of resistance r4 is all connected with pwm controller anti-phase error input, and the other end of adjustable resistance r4 is connected to ground, institute
The first complementary output end stating pwm controller is connected with the grid of field effect transistor q1, the second complementary output end of pwm controller with
The grid of field effect transistor q2 connects, and the drain electrode of described field effect transistor q1 is connected with one end of booster transformer t1 former limit tap, should
The source electrode of field effect transistor q1 respectively with the outside cut-off signals end of pwm controller, one end of resistance r5, field effect transistor q2 source electrode
Connect, the other end of described resistance r5 is connected to ground, the drain electrode of described field effect transistor q2 and booster transformer t1 former limit tap
The other end connects, and the centre cap of this booster transformer t1 is connected with the input of described power supply, filter circuit respectively, described liter
One end of pressure transformer t1 secondary tap is connected with the anode of diode d1, the negative electrode of diode d2 respectively, described boosting transformation
The other end of device t1 secondary tap is connected with the negative pole of electric capacity c3, the positive pole of electric capacity c4 respectively, and the positive pole of described electric capacity c3 is respectively
It is connected with the other end of resistance r3, the negative electrode of diode d1, the input of impulse output circuit, the negative pole of described electric capacity c4 and ground
Connect.
Preferably, described power supply is the DC voltage of 0～36v, and frequency is 30～100khz.
Preferably, the frequency of described pwm controller output is the square-wave pulse signal of 50khz, and this pwm controller adopts
Model sg3525 chip.
Preferably, described impulse output circuit include the first digital driver for isolating, the second digital driver for isolating, first
Power amplifier, the second power amplifier, the 3rd power amplifier, the 4th power amplifier, diode d3, diode d4 and electricity
Hold cn, the drain electrode of described first power amplifier, the drain electrode of the 3rd power amplifier are connected with the outfan of described accumulator,
First power amplifier grid is connected with the first drive output of the first digital driver for isolating, the source of the first power amplifier
Pole is connected with the anode of diode d3, and the negative electrode of described diode d3 is respectively with the drain electrode of the second power amplifier, electrode just
Pole connects, and the negative pole of described electrode is connected with one end of electric capacity, the grid of the second power amplifier and the first numeral isolation drive
Second drive output of device connects, and the source electrode of the second power amplifier is connected to ground, the other end and the 3rd of described electric capacity cn
The source electrode of power amplifier, the anode connection of diode d4, the grid of the 3rd power amplifier and the second digital driver for isolating
The first drive output connect, the negative electrode of described diode d4 is connected with the drain electrode of the 4th power amplifier, described 4th work(
The grid of rate amplifier is connected with the second drive output of the second digital driver for isolating, the source of described 4th power amplifier
Pole is connected to ground, the Enable Pin of described first digital driver for isolating, the ready signal end of the first digital driver for isolating, second
The Enable Pin of digital driver for isolating, the second digital driver for isolating ready signal end respectively with the input of signal controller/
Output control terminal connection, the first input end of the described first digital driver for isolating and the first output control terminal of signal controller
Connect, the first digital second input of driver for isolating is connected with the second output control terminal of signal controller, described second
The first input end of digital driver for isolating is connected with the 3rd output control terminal of signal controller, the second digital driver for isolating
The second input be connected with the 4th output control terminal of signal controller.
Preferably, the described first digital driver for isolating, the second digital driver for isolating adopt model si82390 core
Piece, described first power amplifier, the second power amplifier, the 3rd power amplifier, the 4th power amplifier adopt carborundum
Power mosfet pipe or igbt power tube, the breakdown voltage of this silicon carbide power mosfet pipe or igbt power tube is 1200v.
Preferably, the model c2m0080 power tube that described silicon carbide power mosfet pipe adopts.
In sum, the present invention is due to employing technique scheme, the method have the advantages that
(1), the generator output waveform of the present invention, close to square wave, reduces the generation of heat during surge, and arteries and veins
Rush Parameter adjustable adjusting range width, usage range width, shock pulse voltage amplitude, maximum impulse electricity can be set according to specific requirement
Stream, pulse width, pulse period and pulse number, can be used for, in body and in vitro, reversible and irreversible electroporation experiment, being usually used in
Living cells produce the experimentation of reversibility or irreversible electrical breakdown, electrochemotherapy, gene transfection, oncotherapy etc..
(2), the present invention adopts bridge switching circuit, realizes the dipole inversion of output pulse, by silicon carbide power
Mosfet switching technique, shortens the switching time of switch, improves the frequency of electroporative pulses, colleague is by using capacitor simultaneously
Connection charges, the method for series connection output, reduces the resistance to pressure request to discharge switch and its accessory circuit.
Brief description
In order to be illustrated more clearly that present example or technical scheme of the prior art, below will be to embodiment or existing
Have technology description in required accompanying drawing do simply introduce it should be apparent that, drawings in the following description are only the present invention
Some examples, to those skilled in the art, on the premise of not paying creativeness, can also be attached according to these
Figure obtains other accompanying drawings.
Fig. 1 is a kind of structure principle chart of the pulse generator of cell electroporation of the present invention.
Fig. 2 is the structure principle chart of the power converting circuit of the present invention.
Fig. 3 is the specific works circuit theory diagrams of the power converting circuit of the present invention.
Fig. 4 is the operating circuit schematic diagram of the impulse output circuit of the present invention.
Fig. 5 is a kind of equivalent circuit schematic of the pulse generator of cell electroporation of the present invention.
Fig. 6 is a kind of pulse output waveform figure of the pulse generator of cell electroporation of the present invention.
Specific embodiment
Below in conjunction with the accompanying drawing in present example, the technical scheme in the embodiment of the present invention is carried out clear, complete
Ground description is it is clear that described embodiment is only a part of embodiment of the present invention, rather than whole embodiments.It is based on and send out
Embodiment in bright, the every other enforcement that those of ordinary skill in the art are obtained under the premise of not making creative work
Example, broadly falls into the scope of protection of the invention.
Referring to Fig. 1, a kind of pulse generator of cell electroporation, defeated including power converting circuit 1, accumulator 2, pulse
Go out circuit 3, signal controller 4, electrode 5 and power supply 6, the outfan of described power supply 6 is connected with power converting circuit 1, this power supply
Translation circuit 1 passes sequentially through accumulator 2, impulse output circuit 3 is connected with electrode 5, and described signal controller 4 and pulse export
The control signal of circuit 3 connects, and the control signal being exported by signal controller 4 is thus control the arteries and veins of impulse output circuit 3
Rushing output signal makes electrode 5 be discharged, and described signal controller 4 is controlled using singlechip chip, described power conversion
Circuit 1 is a road, or for more than two-way being connected in parallel, described impulse output circuit 3 is a road, or connects parallel for more than two-way
Connect, be attached with accumulator 2 more than a road or two-way by power converting circuit 1 more than a road or two-way, described
Accumulator 2 is attached with impulse output circuit 3 more than a road or two-way, and in the present invention, accumulator 2 adopts multiple
Electric capacity carries out energy storage in parallel or series, the working method of electric discharge, by power converting circuit 1 more than a road or two-way to multiple
Electric capacity in parallel or series is charged controlling, and to improve the energy stored energy capacitance of accumulator 3, passes through a road or two-way simultaneously
Above impulse output circuit 3 carries out charge and discharge control to multiple electric capacity in parallel or series, is entered with the energy pulse improving output
The discharge magnitude of row coordination electrode 5.Described power supply 6 exports the DC voltage of 0～36v, and frequency is 30～100khz, the present invention
In, described power supply 6 specifically adopts the DC voltage of 24v, and frequency is 50khz, and power supply 6 exported after AC-DC converter+
24v DC voltage, then carry out the charge and discharge control that rectification and voltage multiplier completes to accumulator 2, to guarantee to export the amplitude of pulse, storage
High energy pulse can be provided through impulse output circuit 3 for electrode 5 by circuit 2, in order to improve the pulse width of impulse output circuit 3 output
Degree, pressure, the raising velocity of discharge of the discharge switch reducing in output circuit, according to the requirement of output waveform parameter, pulse is defeated
Go out circuit 3 and the energy storing in storage capacitor is released to histiocyte through electrode 5, signal controller 4 is impulse output circuit 3
Trigger is provided.
In embodiments of the present invention, as shown in Figures 2 and 3, described power converting circuit 1 include pulse-width modulation circuit 100,
Booster circuit 101, filter circuit 102 and rectification circuit 103, the signal output part of described pulse-width modulation circuit 100 and liter piezoelectricity
The control end on road 101 connects, and the input by filter circuit 102 and described rectification circuit 103 of this booster circuit 101 connects
Connect, described power supply 6 is also connected with the input of described booster circuit 101, filter circuit 102 respectively, described rectification circuit 103
Outfan is connected with accumulator 2；Described pulse-width modulation circuit 100 includes pwm controller ic1, resistance r1, resistance r2, resistance
R3, adjustable resistance r4, resistance r5, electric capacity c1 and electric capacity c2, described booster circuit 101 includes field effect q1, field effect q2 and liter
Pressure transformer t1, described accumulator 2 includes electric capacity c3 and electric capacity c4, and described rectification circuit 103 includes diode d1 and two poles
Pipe d2, one end of described resistance r1 is connected with the oscillating discharge outfan dis of pwm controller ic1, one end of described resistance r2 with
The vibration timing resistor input rt of pwm controller ic1 connects, and one end of electric capacity c1 is electric with the vibration timing of pwm controller ic1
Hold input ct to connect, the other end of the other end, the other end of resistance r2 and electric capacity c1 of described resistance r1 is all connected to ground, institute
State one end of resistance r3, one end of adjustable resistance r4, the centre cap of adjustable resistance r4 all with pwm controller ic1 anti-phase error
Input inv connects, and the other end of adjustable resistance r4 is connected to ground, the first complementary output end outa of described pwm controller ic1
It is connected with the grid of field effect transistor q1, the second complementary output end outb of pwm controller ic1 is connected with the grid of field effect transistor q2
Connect, the drain electrode of described field effect transistor q1 is connected with one end of booster transformer t1 former limit tap, and the source electrode of this field effect transistor q1 divides
Not it is not connected with the outside cut-off signals end sd of pwm controller (ic1), one end of resistance r5, the source electrode of field effect transistor q2, described electricity
The other end of resistance r5 is connected to ground, and the drain electrode of described field effect transistor q2 is connected with the other end of booster transformer t1 former limit tap,
The centre cap of this booster transformer t1 is connected with the input of described power supply 6, filter circuit 102 respectively, described boosting transformation
One end of device t1 secondary tap is connected with the anode of diode d1, the negative electrode of diode d2 respectively, described booster transformer t1 pair
The other end of side tap is connected with the negative pole of electric capacity c3, the positive pole of electric capacity c4 respectively, the positive pole of described electric capacity c3 respectively with resistance
The other end of r3, the negative electrode of diode d1, the input of impulse output circuit 3 connect, and the negative pole of described electric capacity c4 is connected to ground,
The frequency of described pwm controller ic1 output is the square-wave pulse signal of 50khz, the model that this pwm controller ic1 adopts
Sg3525 chip.
In the present invention, as shown in figure 3, using described pwm controller ic1 and its auxiliary element resistance r2, resistance r1 and
Electric capacity c1 constitutes pwm control circuit and is timed electric discharge adjustment, and output two-way frequency is the square-wave pulse of 50khz, this pulse
Width is subject on the outfan e/aout (the 9th pin of pwm controller ic1) of pwm controller ic1 internal error amplifier
The control of voltage, field effect q1, field effect q2 and booster transformer t1 composition push-pull type translation circuit, just power supply 6 output+
The square-wave pulse that 24v DC voltage is converted into 50khz is applied to the former limit of booster transformer t1, and in booster transformer t1 secondary
Generation amplitude is 400v, frequency is the square-wave pulse of 50khz；Diode d1, diode d2 and electric capacity c3, electric capacity c4 constitute multiplication of voltage
Formula rectification circuit, it will charge to electric capacity c3, electric capacity c4 after the output impulse commutation of booster transformer t1 secondary, electric capacity c3, electricity
As energy-storage capacitor, the bleeder circuit that resistance r3 and adjustable resistance r4 is constituted is used for detecting the series equivalent capacitance holding c4 composition
The voltage at energy-storage capacitor two ends, and feed back to the anti-phase error input inv (of pwm controller ic1 internal error amplifier
One pin), adjustable resistance r4 can change the charge value of storage capacitor, makes the anti-of pwm controller (ic1) internal error amplifier
Phase input inv (first pin) keeps equal with 5v reference voltage, and the homophase of pwm controller ic1 internal error amplifier is defeated
Enter to hold ni (second pin) to be connected with reference edge vref (the 16th pin)；Pwm controller ic1 internal error amplifier is same to it
Voltage in phase input ni (second pin) and inverting input inv (the first pin) is compared, and according between them
Potential difference to change the outfan e/a out of pwm controller ic1 internal error amplifier, (the 9th of pwm controller ic1 draws
Foot) on voltage, make whole circuit form negative feedback, in order to stablize the voltage on storage capacitor, resistance r5 is current detecting electricity
Resistance, the source current of field effect transistor q1, field effect transistor q2 is converted into voltage by it, and delivers to the pass broken ends of fractured bone sd of pwm controller ic1
(the tenth pin), to limit maximum charging current.When the voltage at resistance r5 two ends reaches 1v, pwm controller ic1 is immediately by field
Effect pipe q1, field effect transistor q2 turn off, and start until the next working cycle.
In embodiments of the present invention, as shown in figure 4, described impulse output circuit 3 includes the first digital driver for isolating
Ic2, the second digital driver for isolating ic3, the first power amplifier san, the second power amplifier sbn, the 3rd power amplifier
Scn, the 4th power amplifier sdn, diode d3, diode d4 and electric capacity cn, the drain electrode of described first power amplifier san,
The drain electrode of the 3rd power amplifier scn is connected with the outfan of described accumulator 2, the first power amplifier san grid and
First drive output voa1 connection, the source electrode of the first power amplifier san and the diode d3 of one digital driver for isolating ic2
Anode connect, the negative electrode of described diode d3 is connected with the drain electrode of the second power amplifier sbn, the positive pole of electrode 5 respectively, institute
The negative pole stating electrode 5 is connected with one end of electric capacity cn, the grid of the second power amplifier sbn and the first digital driver for isolating
Second drive output vob1 of ic2 connects, and the source electrode of the second power amplifier sbn is connected to ground, and described electric capacity cn's is another
End is connected with the source electrode of the 3rd power amplifier scn, the anode of diode d4, the grid and second of the 3rd power amplifier scn
First drive output voa2 connection, the negative electrode of described diode d4 and the 4th power amplifier of digital driver for isolating ic3
The drain electrode of sdn connects, and second driving of the grid of described 4th power amplifier sdn driver for isolating ic3 digital with second is defeated
Go out to hold vob2 to connect, the source electrode of described 4th power amplifier sdn is connected to ground, the described first digital driver for isolating ic2's
Enable Pin en1, the ready signal end rdy1 of the first digital driver for isolating ic2, the Enable Pin of the second digital driver for isolating ic3
En2, ready signal end rdy2 input/output control end i/ with signal controller 4 respectively of the second digital driver for isolating ic3
O connects, and the first input end via1 of the described first digital driver for isolating ic2 is controlled with the first output of signal controller 4 (ic4)
Outa connection in end processed, the second input vib1 of the first digital driver for isolating ic2 and the second output control of signal controller 4
End outb connects, and the first input end via2 of the described second digital driver for isolating ic3 exports control with the 3rd of signal controller 4
Outc connection in end processed, the second input vib2 of the second digital driver for isolating ic3 and the 4th output control of signal controller 4
End outd connects.
In conjunction with shown in Fig. 2 and Fig. 3, described pwm controller ic1 is according to the control instruction of output pulse, pwm controller ic1
The first complementary output end outa, the second complementary output end outb, the 3rd complementary output end outc, the 4th complementary output end outd
Output high level or low level respectively, during output high level, corresponding field effect q1, field effect q2 turn on, during output low level,
Field effect q1, field effect q2 conducting correspondingly ends, and signal microcontroller 4 can also be controlled by input/output control end i/o
First digital driver for isolating ic2, Enable Pin en1 of the second digital driver for isolating ic3 and en2, input/output control end i/
During o output high level, Enable Pin en1 and en2 are activated, the first digital driver for isolating ic2, the second digital driver for isolating
Ic3 works, and when Enable Pin en1 and en2 low level, the first digital driver for isolating ic2, the second digital driver for isolating ic3 stop
Only work, additionally, for making signal controller 4 (ic4) can detect that the first digital driver for isolating ic2, the second numeral isolation drive
The reliability to improve control for the ready signal rdy of ready signal end rdy1, rdy2 output of dynamic device ic3, the first numeral isolation
The model numeral driver for isolating si82390 chip that driver ic2, the second digital driver for isolating ic3 adopt, this driver
Two driver for isolating are controlled with independent input and combines, be particularly well-suited to drive the power supply mosfet supporting to be up to 5kvrms
With igbt power tube.They have high common mode transient rejection ability (100kv/ μ s), low propagation delay (30ns), and reduce temperature
Degree, aging change and between part, output uvlo fault detect and feedback can be automatically switched off two drivers, thus can have high
Reliability, described first digital driver for isolating ic2, the second digital driver for isolating ic3 also adopt three independent work
Power supply is powered, and one is+5v, and two other is+15v, when three groups of power supplys are all ready, the described first digital isolation drive
Device ic2, the rdy signal of the second digital driver for isolating ic3 are changed into high level, otherwise for low level.Described first power amplification
Device san, the second power amplifier sbn, the 3rd power amplifier scn, the 4th power amplifier sdn adopt silicon carbide power
Mosfet pipe or igbt power tube, the model c2m0080 power tube that described silicon carbide power mosfet pipe adopts, it is possible to provide high
Speed switching.The drain-source breakdown voltage of this silicon carbide power mosfet pipe or igbt power tube is 1200v, and the time of switch is less than
0.1 μ s, conducting resistance is 80m ω, and pulse current is up to 80a.Electric capacity cn adopts polypropylene film capacitor, has good temperature
Degree stability, ensures capacitor reliably working, noninductive characteristic, can bear very high peak-to-peak value electric current and high frequency virtual value electric current,
Diode d3, diode d4 are SiC schottky diode, and when being used for preventing from exporting negative pulse, electric current is from switching tube (i.e.
Described the first power amplifier san, the second power amplifier sbn, the 3rd power amplifier scn, the 4th power amplifier
Sdn in internal diode), power filtering capacitor c1_1, electric capacity c1_2, electric capacity c1_3, electric capacity c1_4, electric capacity c1_5 and electricity
Hold c1_6 and adopt tantalum electric capacity, for eliminating the interference that voltage transient causes, therefore, the bi-directional square wave of the exportable ± 4kv of the present invention
Pulse, the rise time of pulse and fall time are less than 1 μ s, and pulse width is from 2 μ s～1000 μ s, continuously adjustabe, pulse current
Peak value is up to 80a.
In conjunction with Fig. 3, Fig. 4 and Fig. 5, when power converting circuit 1 is that more than two-way is connected in parallel, and described pulse output
When circuit 3 is that more than two-way is connected in parallel, accumulator 2 carries out the work of energy storage in parallel or series, electric discharge using multiple electric capacity
Mode, according to the requirement of output waveform parameter, the energy storing in storage capacitor is released to by impulse output circuit 3 through electrode 5
Histiocyte, signal controller 4 provides trigger for impulse output circuit 3.In conjunction with Fig. 5, wherein, Fig. 5 is in Fig. 3 and Fig. 4
Power converting circuit 1, accumulator 2 and impulse output circuit 3 connect after equivalent circuit, as shown in figure 5, described energy storage is electric
Electric capacity c3 in road 2 and electric capacity c4 is equivalent to capacitor cn0, electric capacity cn1～electric capacity cnn and constitutes times voltage capacitance, pulse output electricity
Routing switch sao, switch sbo, sco, switch scdo, switch sa1～switch san, switch sb1～switch sbn, switch sc1～
Switch scn, switch sd1～switch sdn is constituted.Wherein, field effect transistor q1, field effect transistor q2 are equivalent to switch sao, switch respectively
Sbo, and also be equivalent to switch sco, switch scdo, the first power amplifier san be equivalent to switch sa1～switch san, second
Power amplifier sbn be equivalent to switch sb1～switch sbn, the 3rd power amplifier scn be equivalent to switch sc1～scn, the 4th
Power amplifier sdn is equivalent to switch sd1～switch sdn；By switch sa1, switch sb1, switch sc1, switch scd1～switch
San, switch sbn, switch scn and switch sdn connect into n bridge circuit, according to charge or discharge state by capacitor cn0,
Cn1～electric capacity cnn connects into mode in parallel or series, according to the state of switch, as shown in fig. 6, output cathode or polarity arteries and veins
Punching.Switch sao, switch sbo and switch sco, switch scdo respectively constitute two half-bridge circuits, for selecting the pole of output pulse
Property, that is, positive pulse and negative pulse can obtain double-polarity control pulse when replacing output, only export positive pulse, or only export positive arteries and veins
When rushing, unipolar output pulse can be obtained, unipolarity square wave is a kind of the most frequently used waveform, bipolar square wave has symmetry,
More uniform electroporation can be produced on cell membrane, square wave cell electroporation pulse generator can produce single-phase ripple, bi-phase wave,
Can meet in vitro and study, as shown in figure 5, its work process is as follows in body electroporation experiment: in charging process, switch sc1
The scn conducting of～switch, by the positive pole of electric capacity (+) with the positive pole of power supply vi (+) connect, switch sb1～switch sbn turns on, by electricity
Hold negative pole and the power supply vi of cn0 negative pole (-) connect, make capacitor cn1～cn all be filled with supply voltage vi, now, switch sa1
～switch san and switch sd1～switch sdn cut-off, switch sao, switch sbo, switch sco, switch scdo are also switched off.In electric discharge
During, the state of switch is determined according to the polarity of output pulse, as shown in fig. 6, when output cathode pulse, switch
Sdo turns on, and the earth terminal of output is connected with the negative pole of electric capacity cn0, and the positive pole of outfan vo and electric capacity cnn is connect by sao conducting
Logical, switch sb1～switch sbn conducting, the negative pole of a rear electric capacity cnn is connected with the positive pole of previous electric capacity.By keeping
Other switches are in by state.It is the positive pulse of n times of vi therefore in outfan output amplitude, when output negative pole pulse
When, the earth terminal of output is connected by switch sco conducting with the positive pole of electric capacity cn0, and switch sbo turns on outfan vo and electric capacity
The negative pole of cnn is connected, switch sd1～switch sdn conducting, and the positive pole of a rear electric capacity is connected with the negative pole of previous electric capacity,
It is in by state by keeping other switches, be the negative pulse of n times of vi therefore in outfan output amplitude, due to switching structure
The electric bridge becoming is in parallel with electric capacity, and the voltage of each electric capacity is vi, so the maximum voltage that switching tube bears is vi.Relatively low pressure
Power switch there is higher switch speed, and advantage of lower cost.
The foregoing is only the preferred embodiment of invention, not in order to limit the present invention, all spirit in the present invention
Within principle, any modification, equivalent substitution and improvement made etc., should be included within the scope of the present invention.
Claims (9)
1. a kind of pulse generator of cell electroporation it is characterised in that include power converting circuit (1), accumulator (2),
Impulse output circuit (3), signal controller (4), electrode (5) and power supply (6), the outfan of described power supply (6) and power conversion
Circuit (1) connects, and this power converting circuit (1) passes sequentially through accumulator (2), impulse output circuit (3) with electrode (5) even
Connect, described signal controller (4) is connected with the control signal of impulse output circuit (3), is exported by signal controller (4)
Control signal is thus control the pulse output signals of impulse output circuit (3) so that electrode (5) is discharged.
2. a kind of pulse generator of cell electroporation according to claim 1 is it is characterised in that described power conversion is electric
Road (1) is a road, or for more than two-way being connected in parallel, described impulse output circuit (3) is a road, or connects parallel for more than two-way
Connect, be attached with accumulator (2) more than road or two-way by power converting circuit (1) more than road or two-way,
Described accumulator (2) is attached with impulse output circuit (3) more than road or two-way.
3. a kind of pulse generator of cell electroporation according to claim 1 and 2 is it is characterised in that described power supply becomes
Change circuit (1) and include pulse-width modulation circuit (100), booster circuit (101), filter circuit (102) and rectification circuit (103), institute
The signal output part stating pulse-width modulation circuit (100) is connected with the control end of booster circuit (101), this booster circuit (101)
Be connected with the input of described rectification circuit (103) by filter circuit (102), described power supply (6) also respectively with described boosting
Circuit (101), the input of filter circuit (102) connect, and the outfan of described rectification circuit (103) is with accumulator (2) even
Connect.
4. a kind of pulse generator of cell electroporation according to claim 3 is it is characterised in that described pulsewidth modulation is electric
Road (100) includes pwm controller (ic1), resistance r1, resistance r2, resistance r3, adjustable resistance r4, resistance r5, electric capacity c1 and electric capacity
C2, described booster circuit (101) includes field effect q1, field effect q2 and booster transformer t1, and described accumulator (2) includes electricity
Hold c3 and electric capacity c4, described rectification circuit (103) includes diode d1 and diode d2, one end of described resistance r1 is controlled with pwm
The oscillating discharge outfan (dis) of device (ic1) processed connects, the vibration timing of one end of described resistance r2 and pwm controller (ic1)
Resistance input (rt) connects, and one end of electric capacity c1 is connected with vibration timing capacitor input (ct) of pwm controller (ic1),
The other end of the other end, the other end of resistance r2 and electric capacity c1 of described resistance r1 is all connected to ground, one end of described resistance r3,
One end of adjustable resistance r4, the centre cap of adjustable resistance r4 are all connected with the anti-phase error input of pwm controller (ic1) (inv)
Connect, the other end of adjustable resistance r4 is connected to ground, first complementary output end (outa) of described pwm controller (ic1) is imitated with field
Should the grid of pipe q1 connect, second complementary output end (outb) of pwm controller (ic1) is connected with the grid of field effect transistor q2,
The drain electrode of described field effect transistor q1 is connected with one end of booster transformer t1 former limit tap, the source electrode of this field effect transistor q1 respectively with
The outside cut-off signals end (sd) of pwm controller (ic1), one end of resistance r5, the source electrode of field effect transistor q2 connect, described resistance
The other end of r5 is connected to ground, and the drain electrode of described field effect transistor q2 is connected with the other end of booster transformer t1 former limit tap, should
The centre cap of booster transformer t1 is connected with the input of described power supply (6), filter circuit (102) respectively, described liter of buckling
One end of depressor t1 secondary tap is connected with the anode of diode d1, the negative electrode of diode d2 respectively, described booster transformer t1
The other end of secondary tap is connected with the negative pole of electric capacity c3, the positive pole of electric capacity c4 respectively, the positive pole of described electric capacity c3 respectively with electricity
The other end of resistance r3, the negative electrode of diode d1, the input connection of impulse output circuit (3), the negative pole of described electric capacity c4 and ground
Connect.
5. a kind of pulse generator of cell electroporation according to claim 4 is it is characterised in that described power supply (6) is 0
The DC voltage of～36v, frequency is 30～100khz.
6. a kind of pulse generator of cell electroporation according to claim 4 is it is characterised in that described pwm controller
(ic1) frequency exporting is the square-wave pulse signal of 50khz, the model sg3525 chip that this pwm controller (ic1) adopts.
7. a kind of pulse generator of the cell electroporation according to claim 1 or 2 or 4 is it is characterised in that described pulse
Output circuit (3) includes the first digital driver for isolating (ic2), the second digital driver for isolating (ic3), the first power amplifier
(san), the second power amplifier (sbn), the 3rd power amplifier (scn), the 4th power amplifier (sdn), diode d3, two
Pole pipe d4 and electric capacity cn, the drain electrode of described first power amplifier (san), the drain electrode of the 3rd power amplifier (scn) with described
The outfan of accumulator (2) connects, and the of the first power amplifier (san) grid and the first numeral driver for isolating (ic2)
One drive output (voa1) connects, and the source electrode of the first power amplifier (san) is connected with the anode of diode d3, described two poles
The negative electrode of pipe d3 is connected with the drain electrode of the second power amplifier (sbn), the positive pole of electrode (5) respectively, the negative pole of described electrode (5)
It is connected with one end of electric capacity cn, the second drive of the grid of the second power amplifier (sbn) and the first digital driver for isolating (ic2)
Dynamic outfan (vob1) connects, and the source electrode of the second power amplifier (sbn) is connected to ground, the other end and the 3rd of described electric capacity cn
The source electrode of power amplifier (scn), the anode connection of diode d4, the grid of the 3rd power amplifier (scn) and the second numeral
First drive output (voa2) connection, the negative electrode of described diode d4 and the 4th power amplifier of driver for isolating (ic3)
(sdn) the second of drain electrode connection, the grid of described 4th power amplifier (sdn) and the second digital driver for isolating (ic3)
Drive output (vob2) connects, and the source electrode of described 4th power amplifier (sdn) is connected to ground, and described first numeral isolation is driven
The Enable Pin (en1) of dynamic device (ic2), the ready signal end (rdy1) of the first digital driver for isolating (ic2), the second numeral isolation
The Enable Pin (en2) of driver (ic3), the second digital driver for isolating (ic3) ready signal end (rdy2) respectively with signal
The input/output control end (i/o) of controller (4) connects, the first input end of the described first digital driver for isolating (ic2)
(via1) it is connected with first output control terminal (outa) of signal controller (4), the second of the first digital driver for isolating (ic2)
Input (vib1) is connected with second output control terminal (outb) of signal controller (4), the described second digital driver for isolating
(ic3) first input end (via2) is connected with the 3rd output control terminal (outc) of signal controller (4), the second numeral isolation
Second input (vib2) of driver (ic3) is connected with the 4th output control terminal (outd) of signal controller (4).
8. a kind of cell electroporation according to claim 7 pulse generator it is characterised in that described first numeral every
Adopt model si82390 chip, described first power amplifier from driver (ic2), the second digital driver for isolating (ic3)
(san), the second power amplifier (sbn), the 3rd power amplifier (scn), the 4th power amplifier (sdn) adopt carborundum work(
Rate mosfet pipe or igbt power tube, the breakdown voltage of this silicon carbide power mosfet pipe or igbt power tube is 1200v.
9. a kind of pulse generator of cell electroporation according to claim 8 is it is characterised in that described silicon carbide power
The model c2m0080 power tube that mosfet pipe adopts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610898167.3A CN106357246B (en) | 2016-10-14 | 2016-10-14 | Pulse generator for cell electroporation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610898167.3A CN106357246B (en) | 2016-10-14 | 2016-10-14 | Pulse generator for cell electroporation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106357246A true CN106357246A (en) | 2017-01-25 |
| CN106357246B CN106357246B (en) | 2024-09-03 |
Family
ID=57866611
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610898167.3A Active CN106357246B (en) | 2016-10-14 | 2016-10-14 | Pulse generator for cell electroporation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106357246B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106877729A (en) * | 2017-03-24 | 2017-06-20 | 上海健康医学院 | A kind of irreversible electroporation apparatus of high frequency |
| CN109777732A (en) * | 2019-01-17 | 2019-05-21 | 重庆大学 | A kind of bipolar cells fusion instrument and its control method |
| CN112713880A (en) * | 2020-12-21 | 2021-04-27 | 上海联影医疗科技股份有限公司 | Pulse circuit and electron gun |
| CN113346720A (en) * | 2021-06-21 | 2021-09-03 | 东莞市凌风科技有限公司 | High-frequency driving amplifier, high-frequency power conversion circuit and radio frequency cosmetic instrument |
| CN116865589A (en) * | 2023-05-18 | 2023-10-10 | 柔脉医疗(深圳)有限公司 | Portable electric conversion equipment and method based on inductance boost circuit |
| CN116915218A (en) * | 2023-09-11 | 2023-10-20 | 苏州浪潮智能科技有限公司 | pulse power system |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1403173A (en) * | 2002-10-20 | 2003-03-19 | 浙江大学 | Electric perforating system for transdermal medication |
| CN202458657U (en) * | 2011-09-06 | 2012-10-03 | 上海理工大学 | Irreversible electronic perforating device circuit |
-
2016
- 2016-10-14 CN CN201610898167.3A patent/CN106357246B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1403173A (en) * | 2002-10-20 | 2003-03-19 | 浙江大学 | Electric perforating system for transdermal medication |
| CN202458657U (en) * | 2011-09-06 | 2012-10-03 | 上海理工大学 | Irreversible electronic perforating device circuit |
Non-Patent Citations (1)
| Title |
|---|
| 周平;单纯玉;杨澄;: "高压方波不可逆电穿孔肿瘤消融装置的研制", 现代制造工程, no. 03, 18 March 2013 (2013-03-18), pages 116 - 117 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106877729A (en) * | 2017-03-24 | 2017-06-20 | 上海健康医学院 | A kind of irreversible electroporation apparatus of high frequency |
| CN109777732A (en) * | 2019-01-17 | 2019-05-21 | 重庆大学 | A kind of bipolar cells fusion instrument and its control method |
| CN109777732B (en) * | 2019-01-17 | 2020-12-18 | 重庆大学 | Bipolar cell fusion instrument and control method thereof |
| CN112713880A (en) * | 2020-12-21 | 2021-04-27 | 上海联影医疗科技股份有限公司 | Pulse circuit and electron gun |
| CN113346720A (en) * | 2021-06-21 | 2021-09-03 | 东莞市凌风科技有限公司 | High-frequency driving amplifier, high-frequency power conversion circuit and radio frequency cosmetic instrument |
| CN116865589A (en) * | 2023-05-18 | 2023-10-10 | 柔脉医疗(深圳)有限公司 | Portable electric conversion equipment and method based on inductance boost circuit |
| CN116915218A (en) * | 2023-09-11 | 2023-10-20 | 苏州浪潮智能科技有限公司 | pulse power system |
| CN116915218B (en) * | 2023-09-11 | 2024-06-28 | 苏州浪潮智能科技有限公司 | Pulse power system |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106357246B (en) | 2024-09-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106357246A (en) | Pulse generator for cell electroporation | |
| CN106388929A (en) | Isolated type square wave irreversible electroporation apparatus | |
| CN106877729A (en) | A kind of irreversible electroporation apparatus of high frequency | |
| CN206548596U (en) | A kind of irreversible electroporation apparatus of isolated square wave | |
| CN106264723B (en) | Cascade square wave irreversible electroporation instrument | |
| US9056207B2 (en) | Biphasic defibrillation circuit and defibrillator | |
| CN206180984U (en) | Pulse generating circuit of cell electroporation | |
| CN204131481U (en) | The low-loss high speed push-pull driver circuit of low cost | |
| CN206992984U (en) | A kind of irreversible electroporation apparatus of high frequency | |
| CN112737395B (en) | Bipolar all-solid-state LTD square wave pulse generating circuit | |
| CN112336448A (en) | Irreversible electroporation circuit and irreversible electroporation apparatus for heart | |
| CN206355132U (en) | A kind of tandem type square wave irreversibility electroporation circuit | |
| CN204518108U (en) | Electromagnetic Heating control circuit and electromagnetic appliance | |
| CN206226317U (en) | The integrated three-level dual-buck half-bridge inverter of magnetic | |
| CN209269860U (en) | A kind of nano-knife tumour ablation control device | |
| CN106602883A (en) | Power MOS pipe switch power supply integration power supply circuit without auxiliary winding | |
| CN207283434U (en) | A kind of momentary high power electric flux transfer pulse device | |
| CN207426992U (en) | A kind of Sofe Switch isolated inverter of quick response | |
| CN203154608U (en) | Bidirectional defibrillation waveform generating circuit | |
| CN112439128B (en) | Ultra-low voltage energy storage type cardiac defibrillator | |
| CN108471255A (en) | A kind of arbitrary polarity high-voltage square-wave superimposed pulses device | |
| CN204031103U (en) | IGBT grid protection circuit and induction cooker | |
| CN207459981U (en) | Switching power source control circuit and Switching Power Supply | |
| CN110492749A (en) | A kind of full-bridge soft handover nano-knife pulse generating circuit | |
| CN207720105U (en) | A kind of switch tube driving circuit of isolation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20210120 Address after: 201616 12 buildings, 3 floors, No. 1, 618 Lane, Zhongde Road, Xiaokunshan Town, Songjiang District, Shanghai Applicant after: Shanghai Bekada Medical Technology Co.,Ltd. Address before: Science and Technology Department of Shanghai Health Medical College, 279 Zhouzhu Road, Pudong New Area, Shanghai, 201318 Applicant before: SHANGHAI University OF MEDICINE&HEALTH SCIENCES |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |