CN101019779A - Tumor treating steep pulse equipment and process - Google Patents
Tumor treating steep pulse equipment and process Download PDFInfo
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- CN101019779A CN101019779A CN 200710078282 CN200710078282A CN101019779A CN 101019779 A CN101019779 A CN 101019779A CN 200710078282 CN200710078282 CN 200710078282 CN 200710078282 A CN200710078282 A CN 200710078282A CN 101019779 A CN101019779 A CN 101019779A
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Abstract
The present invention is tumor treating steep pulse equipment and process, and belongs to the field of tumor treating technology. The tumor treating steep pulse equipment includes one steep pulse generating, measuring and controlling system, one computer system, one power source system, and one control console. The tumor treating steep pulse equipment with tumor treating electrodes is used for program tumor treatment, and ns level steep pulse is applied to the tumor tissue, so as to destroy and kill tumor cell irreversibly through electric shock. The present invention has high treatment effect, no side effect caused by chemotherapeutic medicine and simple operation, and may be used widely for the tumor treatment of human body and animal.
Description
Technical field
The invention belongs to the oncotherapy technical field, relate in particular to the devices and methods therefor of treatment tumor.
Background technology
The method that is used for the treatment of tumor at present mainly contains: excision, radiotherapy, chemotherapy, thermotherapy etc.These methods are owing to the restriction that is subjected to factors such as its indication, contraindication and side effect, and are still not ideal enough to the curative effect of tumor.
The pulse electrochemical therapy is the new technique of the treatment tumor that grew up in nearly 30 years, by Japanese scholar M.Okino in initiative in 1987.Therapeutic Method is to carry out intramuscular injection earlier through intravenously administrable or around tumor tissues, give the chemotherapeutics (as rich Lay enzyme element, cisplatin etc.) of tumor cell doses, square wave electric pulse (4～10 of peak value 1～2kV/cm, pulsewidth 100 μ s, frequency 1～4Hz, the pulse number) auxiliary treatment of doses is introduced in a period of time (4～30 minutes) back by electrode.Under normal physiological function situation, cell membrane can hinder the transmission of ion and hydrophilic molecules preferably.But, be kV/cm level, persistent period to be the electric pulse of ms～μ s level during when applying electric field intensity in cell, topographical variations can take place in cell membrane, a large amount of micropores occur, and the electrical conductivity of cell membrane and penetrating ability are increased sharply, and this phenomenon is called as the electroporation phenomenon.The result of cell membrane electroporation is that the inside and outside molecule exchange of cell has significant increase, helps cell and absorbs macromole such as various medicines, DNA, protein.The pulse electrochemical therapy utilizes electric pulse to cause the cell membrane electroporation just, thereby promotes transporting of chemotherapeutics, improves the lethality of chemotherapeutics.Therefore, the pulse electrochemical therapy electroporation therapy that is otherwise known as.
Electroporation therapy has been applied to the clinical treatment of tumor the America and Europe.For example, the MedPulser electroporation treatment system that American I novio company produces has obtained U.S. FDA in 2003 approval enters the III clinical trial phase of head and neck cancer and skin carcinoma, this system is by electric pulse generator, foot switch, electrode tip and mini-printer (optional) are formed, its electric pulse generator is by transformator, high-voltage power translation circuit and low pressure digital control circuit are formed, can produce 6 peak values is 500～1500V, pulsewidth is the potential pulse of 100 μ s, its method is to inject chemotherapeutics (winning syphilis) to patient's tumor tissues earlier, in tumor tissues, insert electrod-array after ten minutes, and depress foot switch, export electric pulse between the electrode needle tumor tissues.The CLINIPORATOR electroporation treatment system that Italy IGEA company produces has been applied to the clinical treatment of superficial tumor in states such as Italy, France, Slovenia, this system is made up of electric pulse generator, foot switch, electrode tip, portable computer, printer and frame, it is that 500～1000V, pulsewidth are that 30 μ s～5ms, repetition rate are the potential pulse of 1Hz～5kHz that its electric pulse generator can produce 8～20 peak values, and its Therapeutic Method is the same.Though the pulse electrochemical therapy has obtained noticeable effect in the clinical treatment of tumor, this therapy has been the assosting effect that strengthens chemotherapeutical medicine curative effect, can not fundamentally avoid the harm of the side effect of chemotherapeutics to patient body.
Summary of the invention
The objective of the invention is to: at the deficiency of existing pulse electrochemical therapy, the device and method of a kind of tumor treating steep pulse that provides.The present invention is under the situation of not injecting chemotherapeutics, apply steepness and be nanosecond (ns) level, heavy dose of exponential damping electric pulse in tumor tissues, make tumor cell generation irreversibility electrical breakdown (IREB) and death, anti-angiogenic effect, immunological effect and the apoptosis effect etc. of simultaneous excitation body, thus reach therapeutic effect.The present invention is the auxiliary treatment role transformation of electric pulse in the pulse electrochemotherapy main treatment means, can eliminate the side effect of chemotherapeutics, simplifies therapeutic process.
The principle of apparatus of the present invention: the core component of apparatus of the present invention is that steep-sided pulse takes place and TT﹠C system, this system mainly measures the pre-process unit by steep-sided pulse generating unit, steep-sided pulse control unit and steep-sided pulse and forms, and computer system is as the terminal of its measurement and control.In the steep-sided pulse generating unit, the civil power (220V/50Hz) of input becomes high voltage direct current about 310V through full-bridge rectification, forward converter becomes this DC voltage the high frequency square wave pulse of 40kHz, with this square-wave pulse rectification unidirectional current of getting back, this DC voltage charges to electric capacity through resistance, and the electric capacity that is full of electricity can output index decay steep-sided pulse to load discharge through the steepness circuit.In the steep-sided pulse control unit, the low pressure square-wave pulse that pulse width modulation (PWM) circuit generation repetition rate and pulse width all can be regulated arbitrarily, this square-wave pulse isolated and drive the square-wave pulse obtain identical repetition rate and pulse width, this square-wave pulse just can be used to control the switching component in the forward converter circuit and capacitor charge and discharge loop in the steep-sided pulse generating unit.The size of adjustable resistance (Rw21) in the pwm circuit of adjusting steep-sided pulse control unit, can change the dutycycle of pwm circuit chips (IC21) output square-wave pulse, with the control signal of this square-wave pulse as switching component (K11) in the steep-sided pulse generating unit forward converter circuit, the peak value of the steep-sided pulse that produced of scalable steep-sided pulse generating unit then; The size of resistance (Rt2) in the pwm circuit of adjusting steep-sided pulse control unit, can change the repetition rate of IC21 output square-wave pulse, with the control signal of this square-wave pulse as switching component (K12, K13) in the steep-sided pulse generating unit capacitor charge and discharge loop, the then repetition rate of the steep-sided pulse that produced of scalable steep-sided pulse generating unit, and this frequency can be determined by formula (1); The size of adjustable resistance (Rw22) in the drive circuit of adjusting steep-sided pulse control unit, can change the resistance of switching component (K13) in the steep-sided pulse generating unit capacitor discharge loop, thereby regulate the rise time of the steep-sided pulse that the steep-sided pulse generating unit is produced; In load (for example tumor tissues) regularly, the input/output signal control card is selected different charge and discharge capacitances by capacitor charge and discharge loop in the control steep-sided pulse generating unit, just can realize regulating the pulse width of steep-sided pulse generating unit output steep-sided pulse.The steep-sided pulse waveform of steep-sided pulse generating unit output is behind decompression transformation, giving steep-sided pulse measurement pre-process unit handles, the signal of handling well is sent into the data collecting card of inside computer system at last and is sampled, and the steep-sided pulse waveform that records is shown to the user by liquid crystal display.The steep-sided pulse that apparatus of the present invention produce is the exponential damping impulse waveform, form by the rising edge of quick increase and the trailing edge of slowly decay, its rising edge has comprised a large amount of low frequency components, mainly act on the cell membrane (but Approximate Equivalent is an electric capacity) of tumor cell, trailing edge has then comprised abundant high fdrequency component, can permeate through cell membranes and act on the film inner cell organs such as nucleus, mitochondrion of tumor cell inside.Therefore, whole exponential damping steep-sided pulse has comprised the utmost point broad spectrum from direct current, low frequency, high frequency to very high frequency(VHF), and can produce general effect to whole tumor cell.
The technical scheme that realizes the object of the invention is: a kind of tumor treating steep pulse device mainly comprises steep-sided pulse generation and TT﹠C system, computer system, power-supply system and bench board.Wherein: steep-sided pulse takes place to measure the pre-process unit with TT﹠C system by steep-sided pulse generating unit, steep-sided pulse control unit and steep-sided pulse and forms, the control signal that the steep-sided pulse control unit produces is connected with the steep-sided pulse generating unit with lead, and the steep-sided pulse signal that the steep-sided pulse generating unit produces is measured the pre-process unit with lead and steep-sided pulse and is connected; Computer system is made up of industrial control computer main frame, liquid crystal display, keyboard and mouse, data collecting card and input/output signal control card, liquid crystal display, keyboard and mouse are connected with lead with the industrial control computer main frame, data collecting card is inserted in the bus slot of industrial control computer main frame, and measure the pre-process unit with steep-sided pulse and link to each other with coaxial cable, the input/output signal control card also is inserted in the bus slot of industrial control computer main frame, and links to each other with data wire with the steep-sided pulse control unit; Power-supply system is made up of isolating transformer, uninterrupted power supply (ups) Unity, linear DC power supply and wiring board, the civil power (220V/50Hz) of input inserts isolating transformer with lead earlier, the outfan of isolating transformer is connected to UPS with lead, the outfan of UPS is connected to wiring board with lead, the outfan of wiring board is connected to linear DC power supply, steep-sided pulse generation and TT﹠C system, industrial control computer main frame and liquid crystal display with power line, and the linear DC power supply takes place to link to each other with power line with TT﹠C system with steep-sided pulse; Bench board is made up of on and off switch, display lamp and steep-sided pulse out splice going splice, and they all take place to link to each other with holding wire with TT﹠C system with steep-sided pulse.Liquid crystal display is installed in the rack top, bench board is installed in the rack upper end, in rack, be equiped with keyboard and mouse, steep-sided pulse generation and TT﹠C system, industrial control computer main frame and power-supply system from top to bottom successively, four jiaos of places, lower end at rack are equiped with universal wheel, be convenient to arbitrarily move, upper end in the rack back is equiped with handle, arbitrarily moves so that promote this device.
The steep-sided pulse that apparatus of the present invention produced is unidirectional exponential damping electric pulse.Regulate the size of adjustable resistance Rw21 in the steep-sided pulse control unit, the peak value of steep-sided pulse is adjustable continuously between 0V～1000V; Regulate the size of resistance R t2 in the steep-sided pulse control unit, the repetition rate of steep-sided pulse is adjustable continuously between 1Hz～10kHz; Regulate the size of adjustable resistance Rw22 in the steep-sided pulse control unit, the rise time of steep-sided pulse is adjustable continuously between 10ns～100ns; Select different charge and discharge capacitances in the steep-sided pulse generating unit, the pulse width of steep-sided pulse between 100ns～100 μ s, divide 6 grades adjustable.Apparatus of the present invention realize accurate control to output steep-sided pulse energy by the adjusting to its output steep-sided pulse above-mentioned parameter just, and the adjusting of these parameters independent separately, do not disturb mutually.Tumor treating steep pulse device of the present invention is by powerful software system, except presetting and regulate to each parameter of output steep-sided pulse, can also gather in real time and demonstration, characteristic parameter are measured in real time the waveform of output steep-sided pulse, and have more perfect patient history Database Systems.
A kind of method of tumor treating steep pulse is utilized tumor treating steep pulse device of the present invention, utilizes the oncotherapy electrode, and the concrete grammar step for the treatment of by program is as follows:
(1) initialization
After the tumor treating steep pulse device start of the present invention, characteristic parameter of initialization steep-sided pulse (being peak value of pulse, repetition rate, pulse width, rise time and treatment time) and program parameter (as waveform acquisition, waveform demonstration, timing time etc.).
(2) determine the treatment parameter
1. formulate therapeutic scheme
(1) step finish after, formulate the corresponding treatment scheme according to patient's the characteristics (health, age, sex etc.) and the concrete condition (kind, grade malignancy, size etc.) of tumor tissues thereof, and the on position and the degree of depth of characteristic parameter of definite steep-sided pulse (being peak value of pulse, repetition rate, pulse width, rise time and treatment time) and electrode tip.
2. preset the treatment parameter
Treatment parameter according to (2)-1. step was determined by the computer system of apparatus of the present invention, presets the treatment parameters such as peak value of pulse, repetition rate, pulse width, rise time and treatment time of tumor treating steep pulse device.
(3) treat
1. insert electrode tip
After finishing in (2) step, the on position and the degree of depth of the electrode tip of determining according to (2)-1. step are inserted electrode tip in the tumor tissues of treatment.
2. treat
(3)-1. the step finish after, enter the KeyEvent determining program: when judged result is " preparation ", then export steep-sided pulse to installing inner fictitious load by input/output signal control card control steep-sided pulse generating unit, and making " preparation " display lamp on the bench board bright by input/output signal control card output control signal, expression can enter " treatment "; When judged result is " treatment ", then organize by the output of the steep-sided pulse out splice going splice on bench board steep-sided pulse to external tumor by input/output signal control card control steep-sided pulse generating unit, and " preparation " display lamp on the bench board is extinguished by input/output signal control card output control signal, " treatment " display lamp is bright, expression enters " treatment ", the log-on data capture card begins to gather the steep-sided pulse waveform simultaneously, the steep-sided pulse waveform is presented in real time on the screen of liquid crystal display, and measures each characteristic parameter (peak value of pulse of steep-sided pulse, repetition rate, pulse width and rise time).Each steep-sided pulse parameter that records and the parameter that preset are originally compared, judge whether to reach preset value: when not reaching preset value, then adjust (increase or reduce) treatment parameter by input/output signal control card control steep-sided pulse control unit, and get back to waveform acquisition and display routine, carry out parameter measurement and comparison once more, repeat this process and equate with preset value until measured value of parameters; When the parameter measured value equates with preset value, then pick up counting, in this process, waveform acquisition and display routine all start always.Treatment time and its preset value are compared: when treatment time did not reach preset value, then timing was proceeded, and continued relatively treatment time and its preset value; When treatment time reaches preset value, then export steep-sided pulse to installing inner fictitious load by input/output signal control card control steep-sided pulse generating unit, and " treatment " display lamp on the bench board is extinguished by input/output signal control card output control signal, expression " treatment " end.
(4) treatment finishes
Finishing in (3)-2. step is after " treatment " display lamp on the bench board extinguishes, to extract electrode tip from tumor tissues, the treatment end.
After the present invention adopts technique scheme, mainly contain following characteristics:
1, the ns level steep-sided pulse waveform of the present invention's employing is the exponential damping electric pulse, waveform is divided into fast rise part and slow sloping portion two parts, its fast rise has partly comprised abundant high fdrequency component, can see through the cell membrane (but Approximate Equivalent is an electric capacity) of tumor cell, act on film inner cell organs such as nucleus, mitochondrion; Its slow sloping portion has then comprised abundant low frequency component, mainly acts on the cell membrane of tumor cell.Therefore, whole steep-sided pulse has comprised the utmost point broad spectrum from direct current, low frequency, high frequency to very high frequency(VHF), and this steep-sided pulse is acted on tumor cell, can produce comprehensive destruction to it.
2, adopt tumor treating steep pulse devices and methods therefor of the present invention, under the situation of not injecting chemotherapeutics, to people's ovary SKOV
3Fresh tumor tissues, 60 lotus tumor BALB/c mouse, 20 lotus tumor Wistar rats and 80 lotus tumor new zealand white rabbits after cancerous cell, 20 example operations are exsomatized are tested.The result shows, steep-sided pulse can cause tumor cell generation irreversibility electrical breakdown and death, anti-angiogenic effect, immunological effect and the apoptosis effect etc. of simultaneous excitation body, destroyed the conditions of existence of tumor, growth of tumor, propagation have obviously been suppressed, therapeutic effect is good, and has fundamentally avoided the harm of the side effect of chemotherapeutics to patient body, demonstrates good potential applicability in clinical practice.
3, apparatus of the present invention are easy to use, and the inventive method is simple to operate.
The present invention can be widely used in the oncotherapy of human body and animal.
Description of drawings:
Fig. 1 is the front view of apparatus of the present invention;
Fig. 2 is the side view of Fig. 1;
Fig. 3 is the structure chart of apparatus of the present invention;
Fig. 4 is the structural representation of bench board, steep-sided pulse generation and TT﹠C system, industrial control computer main frame and the power-supply system of apparatus of the present invention;
Fig. 5 is that the steep-sided pulse of apparatus of the present invention takes place and the TT﹠C system theory diagram;
Fig. 6 is the program flow chart of the inventive method;
Fig. 7 is the steep-sided pulse generating unit circuit theory diagrams of embodiment 1;
Fig. 8 is pulse width modulation (PWM) circuit theory diagrams of the steep-sided pulse control unit of embodiment 1;
Fig. 9 is the drive circuit schematic diagram of the steep-sided pulse control unit of embodiment 1;
Figure 10 is that the steep-sided pulse of embodiment 1 is measured pre-process element circuit schematic diagram;
Figure 11 is the linear DC power circuit schematic diagram of embodiment 1;
Figure 12 is the steep-sided pulse complete waveform figure of embodiment 1;
Figure 13 is the steep-sided pulse rising edge oscillogram of embodiment 1;
Figure 14 does not carry out the cancerous cell electron scanning micrograph for the treatment of steep pulse for embodiment 2;
Figure 15 is the cancerous cell electron scanning micrograph after embodiment 2 carries out treating steep pulse;
Figure 16 is embodiment 3 subcutaneous transplantation human cervical carcinoma U
14BALB/c mouse after one week is carried out the photo before the treating steep pulse;
Figure 17 is embodiment 3 subcutaneous transplantation human cervical carcinoma U
14BALB/c mouse carry out behind the treating steep pulse 3 days photo;
Figure 18 is embodiment 3 subcutaneous transplantation human cervical carcinoma U
14BALB/c mouse carry out behind the treating steep pulse 10 days photo;
Figure 19 is embodiment 3 subcutaneous transplantation human cervical carcinoma U
1417 days the BALB/c mouse in back is not carried out the photo for the treatment of steep pulse;
Figure 20 is embodiment 3 subcutaneous transplantation human cervical carcinoma U
14The tumor growth curve figure of BALB/c mouse;
Among the figure: curve 1 is not for carrying out the tumor growth curve for the treatment of steep pulse;
Figure 21 is embodiment 3 subcutaneous transplantation human cervical carcinoma U
14The survival curve figure of BALB/c mouse;
Among the figure: curve 3 is not for carrying out the survival curve for the treatment of steep pulse;
Among the figure: 1 liquid crystal display, 2 bench boards, 3 keyboard and mouses, 4 racks, 5 universal wheels, 6 handles, 7 steep-sided pulses take place and TT﹠C system, 8 industrial control computer main frames, 9 power-supply systems, 10 nameplate signs, 11 steep-sided pulse out splice going splices, 12 on and off switch, 13 display lamps, 14 coaxial cable interfaces, 15 data line interfaces, 16 dc source interfaces, 17 AC power interfaces, 18 steep-sided pulse generating units, 19 steep-sided pulse control units, 20 steep-sided pulses are measured pre-process unit, 21 data collecting cards, 22 input/output signal control cards, 23 alternating current power supply input interfaces, 24 isolating transformers, 25 uninterrupted power supply (ups) Unitys, 26 wiring boards, 27 linear DC power supplys, 28 holding wires, 29 data wires, 30 coaxial cables, 31 power lines, 32 computer systems.
The specific embodiment:
Below in conjunction with specific embodiments, further specify the present invention.
Embodiment 1:
Shown in Fig. 1～5 and Fig. 7～13, a kind of tumor treating steep pulse device comprises that mainly steep-sided pulse takes place and TT﹠C system 7, computer system 32, power-supply system 9 and bench board 2.Wherein: steep-sided pulse generation and TT﹠C system 7 are by steep-sided pulse generating unit 18, steep-sided pulse control unit 19 and steep-sided pulse are measured pre-process unit 20 and are formed, the control signal that steep-sided pulse control unit 19 produces is connected with steep-sided pulse generating unit 18 with lead, the steep-sided pulse signal that steep-sided pulse generating unit 18 produces is measured pre-process unit 20 with lead and steep-sided pulse and is connected, steep-sided pulse generating unit 18 links to each other with power-supply system 9 with dc source interface 16 usefulness power lines 31 by AC power interface 17, steep-sided pulse control unit 19 links to each other with computer system 2 by data line interface 15 usefulness data wires 29, link to each other with power-supply system 9 by dc source interface 16 usefulness power lines 28, steep-sided pulse is measured pre-process unit 20 and is linked to each other with computer system 2 by coaxial cable interface 14 usefulness coaxial cables 30, link to each other with power-supply system 9 by dc source interface 16 usefulness power lines 31; Computer system 32 is made up of industrial control computer main frame 8, liquid crystal display 1, keyboard and mouse 3, data collecting card 21 and input/output signal control card 22, liquid crystal display 1, keyboard and mouse 3 are connected with industrial control computer main frame 8 usefulness leads, data collecting card 21 is inserted in the bus slot of industrial control computer main frame 8, and measure pre-process unit 20 usefulness coaxial cables 30 with steep-sided pulse and link to each other, input/output signal control card 22 also is inserted in the bus slot of industrial control computer main frame 8, and links to each other with steep-sided pulse control unit 19 usefulness data wires 29; Power-supply system 9 is by isolating transformer 24, UPS25, linear DC power supply 27 and wiring board 26 are formed, the civil power (220V/50Hz) of input inserts isolating transformer 24 by alternating current power supply input interface 23 usefulness leads, the outfan of isolating transformer 24 is connected to UPS25 with lead, the outfan of UPS25 is connected to wiring board 26 with lead, the outfan of wiring board 26 is connected to linear DC power supply 27 with power line 31, steep-sided pulse takes place and TT﹠C system 7, industrial control computer main frame 8 and liquid crystal display 1, linear DC power supply 27 takes place to link to each other with TT﹠C system 7 usefulness power lines 31 with steep-sided pulse; Bench board 2 is made up of on and off switch 12, display lamp 13 and steep-sided pulse out splice going splice 11, and they all take place to link to each other with TT﹠C system 7 usefulness holding wires 28 with steep-sided pulse.
The liquid crystal display 1 of present embodiment device is installed in rack 4 tops, and its inclination angle is according to the user's request flexible; Bench board 2 is installed in rack 4 upper ends on the inclined-plane of certain angle (22.5 degree); In rack 4, be equiped with keyboard and mouse 3, steep-sided pulse generation and TT﹠C system 7, industrial control computer main frame 8 and power-supply system 9 from top to bottom successively; Be provided with Qianmen and back door and two side doors and the external world around the rack 4 and separate, Qianmen and back door all are equiped with automatic locking, after opening, the latch at top of leaving behind can unload it, two side door structures are identical, all fix with four screws, are provided with the two rows air vent on it; Four jiaos of places, lower end at rack 4 are equiped with universal wheel 5, are convenient to arbitrarily move; Upper end in rack 4 back is equiped with handle 6, arbitrarily moves so that promote this device.
The circuit of the steep-sided pulse generating unit 18 of present embodiment device mainly is made up of commercial power rectification filter circuit, forward converter, impulse commutation filter circuit, sampling feedback circuit, capacitor charge and discharge circuit and steepness circuit.The rectification circuit that diode D11, D12, D13 and D14 form is transformed into the high voltage direct current of 310V with the civil power (220V/50Hz) of input, and the filter circuit that capacitor C 11 is formed is transformed into stable high voltage direct current with it.High frequency transformer Tr1, igbt (IGBT) K11 and fast recovery diode D15 constitute the forward converter circuit, the DC voltage about 310V are become the high frequency square wave pulse of 40kHz; High frequency transformer Tr1 comprises ferrite core and enamel-covered wire, realizes the conversion of former and deputy edge-impulse voltage peak, and its former limit links to each other with IGBTK11 with filter capacitor C11, and secondary links to each other with simulation ground with fast recovery diode D15; The colelctor electrode of IGBTK11 links to each other with the former limit of high frequency transformer Tr1, and emitter stage links to each other with filter capacitor C11, and grid links to each other with steep-sided pulse control unit 19; The two ends of fast recovery diode D15 link to each other with filter inductance L1 with the secondary of high frequency transformer Tr1.The impulse commutation filter circuit is made up of fast recovery diode D16, filter inductance L1 and filter capacitor C12, and the high frequency square wave impulse transfer of 40kHz is become stable high voltage direct current; The two ends of fast recovery diode D16 link to each other with simulation ground with fast recovery diode D1 5, and the two ends of filter inductance L1 link to each other with filter capacitor C12 with fast recovery diode D15, and the two ends of filter capacitor C12 link to each other with simulation ground with filter inductance L1.Sampling feedback circuit is made up of resistance R 11 and adjustable resistance Rw1, the two ends of resistance R 11 link to each other with adjustable resistance Rw1 with filter capacitor C12, the two ends of adjustable resistance Rw1 link to each other with simulation ground with resistance R 11, and the intersection point of resistance R 11 and adjustable resistance Rw1 links to each other with steep-sided pulse control unit 19.Capacitor charge and discharge circuit is made of charging resistor R12, IGBT K12, IGBT K13 and capacitor group, and producing the rise time is the exponential damping pulse of hundreds of nanoseconds; The two ends of charging resistor R12 link to each other with the colelctor electrode of resistance R 11 with IGBT K12; The colelctor electrode of IGBT K12 links to each other with charging resistor R12, and emitter stage links to each other with the capacitor group, and grid links to each other with steep-sided pulse control unit 19; The electric capacity that the capacitor group is intended ground by six common modes is formed, and selecting one of them electric capacity by steep-sided pulse control unit 19 is mutual capacitance, links to each other with the emitter stage of IGBT K12 and the colelctor electrode of IGBT K13; The colelctor electrode of IGBT K13 links to each other with the capacitor group, and emitter stage links to each other with capacitor C 13, and grid links to each other with steep-sided pulse control unit 19.The steepness circuit is made up of capacitor C 13, steepness gap S1 and load, reduces the rise time of the exponential damping pulse of capacitor charge and discharge circuit generation; The two ends of capacitor C 13 link to each other with simulation ground with the emitter stage of IGBT K13, and the two ends of steepness gap S1 link to each other with load with capacitor C 13, and the two ends of load link to each other with simulation ground with steepness gap S1.
The pwm control circuit of the steep-sided pulse control unit 19 of present embodiment device is a core with IC 21 (SG1525AJ), produces the low pressure square-wave pulse that repetition rate and pulse width all can be regulated arbitrarily under the cooperation of peripheral resistance capacitance.The intersection point of resistance R 11 and adjustable resistance Rw1 links to each other in one end of resistance R 21 and the steep-sided pulse generating unit 18, and the other end links to each other with 1 foot of IC21.One end of resistance R 22 links to each other with the adjustable side of adjustable resistance Rw21, and the other end links to each other with 2 feet of IC21.The end of adjustable resistance Rw21 links to each other with 16 feet of IC21, and the other end and Gnd1 (digitally 1) link to each other, and the adjustable side links to each other with resistance R 22.The end of capacitor C t2 links to each other with 5 feet of IC21, the other end with digitally 1 link to each other.The end of resistance R t2 links to each other with 6 feet of IC21, the other end with digitally 1 link to each other.The end of resistance R d2 links to each other with 7 feet of IC21, and the other end links to each other with 5 feet of IC21.One end of capacitor C 21 links to each other with 8 feet of IC21, the other end with digitally 1 link to each other.One end of capacitor C 22 links to each other with 9 feet of IC21, and the other end links to each other with resistance R 23.One end of resistance R 23 links to each other with capacitor C 22, and the other end links to each other with 1 foot of IC21.12 feet of IC21 with digitally 1 link to each other, 13 feet and 15 feet all with power Vcc 1 (+15V) link to each other the two-way square-wave pulse signal that 11 feet are opposite with 14 foot output polarities.
The drive circuit of the steep-sided pulse control unit 19 of present embodiment device is a core with IC 22 (TLP250), under the cooperation of peripheral resistance capacitance, the square-wave pulse that pwm control circuit is produced is isolated and is amplified, its output signal links to each other with the grid of three IGBT in the steep-sided pulse generating unit 18, as its control signal.2 feet of IC22 link to each other with 11 feet or 14 feet in the pwm control circuit.One end of resistance R 24 links to each other with 3 feet of IC22, the other end with digitally 1 link to each other.5 feet of IC22 and 8 feet respectively with power supply Vee2 (15V) with Vcc2 (+15V) link to each other.One end of resistance R 25 links to each other with 6 feet of IC22, and the other end and Gnd2 (digitally 2) link to each other.The end of adjustable resistance Rw22 links to each other with 6 feet of IC22, and the adjustable side and the other end are the outfan of drive circuit, links to each other with the grid of three IGBT in the steep-sided pulse generating unit 18.The negative electrode of stabilivolt Z21 links to each other with the outfan of drive circuit, and anode links to each other with the anode of stabilivolt Z22.The anode of stabilivolt Z22 links to each other with the anode of stabilivolt Z21, negative electrode with digitally 2 link to each other.
The steep-sided pulse of present embodiment device is measured the circuit of pre-process unit 20 and is made up of pulses of current sensor, current-voltage (I-V) translation circuit, amplifier stage and operating point servo circuit, the pulsed current signal that steep-sided pulse generating unit 18 produces is handled, and exported to the data collecting card 21 of computer system 2.Pulses of current sensor comprises annular crystallite magnetic core and enamel-covered wire, and the pulsed current signal that steep-sided pulse generating unit 18 produces passes therethrough, and its secondary links to each other with simulation ground with capacitor C 31.The I-V translation circuit is made up of integrated operational amplifier A31, resistance R 31 and R32, and the pulsed current signal that pulses of current sensor is obtained is converted to pulse voltage signal; One end of resistance R 31 links to each other with the inverting input of A31, and the other end links to each other with the outfan of A31; One end of resistance R 32 links to each other with the in-phase input end of A31, and the other end links to each other with simulation ground.Amplifier stage is made up of integrated operational amplifier A32, resistance R 33, R34 and R35, and pulse voltage signal is amplified, and its output links to each other with the data collecting card 21 of computer system 2; One end of resistance R 33 links to each other with the outfan of A31, and the other end links to each other with the inverting input of A32; One end of resistance R 34 links to each other with the inverting input of A32, and the other end links to each other with the outfan of A32; One end of resistance R 35 links to each other with the in-phase input end of A32, and the other end links to each other with simulation ground.The operating point servo circuit is made up of integrated operational amplifier A33, resistance R 36, R37, R38, capacitor C 32, C33 and diode D31, D32, and automatically the operating point adjustment to operational amplifier A 31, A32 makes its static drift approach zero; One end of resistance R 36 links to each other with the outfan of A32, and the other end links to each other with the in-phase input end of A33; One end of capacitor C 32 links to each other with the in-phase input end of A33, and the other end links to each other with simulation ground; The anode of diode D31 links to each other with the in-phase input end of A33, and negative electrode links to each other with simulation ground; The negative electrode of diode D31 links to each other with the in-phase input end of A33, and anode links to each other with simulation ground; One end of resistance R 37 links to each other with the inverting input of A33, and the other end links to each other with simulation ground; One end of capacitor C 33 links to each other with the inverting input of A33, and the other end links to each other with the outfan of A33; One end of resistance R 38 links to each other with the outfan of A33, and the other end links to each other with the in-phase input end of A31.
Embodiment 2:
As shown in Figure 6, the stripped people's ovary SKOV of a kind for the treatment of steep pulse
3The method of cancerous cell is utilized " bundling electrode with integrated positive pole and negative pole of shape memory alloy " of tumor treating steep pulse device of the present invention and the applicant's publication number for CN1810318A, by program to people's ovary SKOV
3The concrete grammar step that cancerous cell is treated is as follows:
(1) initialization
After the tumor treating steep pulse device start of the present invention, characteristic parameter of initialization steep-sided pulse (being peak value of pulse, repetition rate, pulse width, rise time and treatment time) and program parameter (as waveform acquisition, waveform demonstration, timing time etc.).
(2) determine the treatment parameter
1. formulate therapeutic scheme
(1) step finish after, according to people's ovary SKOV
3The characteristics of cancerous cell (exsomatize, malignant tumor, cell suspension) are formulated therapeutic scheme, the characteristic parameter of determining steep-sided pulse is: peak value of pulse 200V, repetition rate 100Hz, pulse width 10 μ s, rise time 100ns, treatment time 20min, it is dark that 1cm is inserted on the vertical cell suspension of electrode tip surface.
2. preset the treatment parameter
According to definite treatment parameter of (2)-1. step, by the computer system 32 of apparatus of the present invention, the peak value of pulse that presets the tumor treating steep pulse device is that 200V, repetition rate are that 100Hz, pulse width are 10 μ s, rise time to be that 100ns, treatment time are 20min.
(3) treat
1. insert electrode tip
After finishing in (2) step, the on position and the degree of depth of the electrode tip of determining according to (2)-1. step are inserted electrode tip stripped people's ovary SKOV of treatment
3In the cancerous cell suspension.
2. treat
(3)-1. the step finish after, enter the KeyEvent determining program: when judged result is " preparation ", then export steep-sided pulses to installing inner fictitious load by input/output signal control card 22 control steep-sided pulse generating units 18, and making " preparation " display lamp on the bench board 2 bright by input/output signal control card 22 output control signals, expression can enter " treatment "; When judged result is " treatment ", then export steep-sided pulses to external tumor cell suspension by the steep-sided pulse out splice going splice on the bench board 2 11 by input/output signal control card 22 control steep-sided pulse generating units 18, and " preparation " display lamp on the bench board 2 is extinguished by input/output signal control card 22 output control signals, " treatment " display lamp is bright, expression enters " treatment ", log-on data capture card 21 begins to gather the steep-sided pulse waveform simultaneously, the steep-sided pulse waveform is presented in real time on the screen of liquid crystal display 1, and measures each characteristic parameter (peak value of pulse of steep-sided pulse, repetition rate, pulse width and rise time).Each steep-sided pulse parameter that records and the parameter that preset are originally compared, judge whether to reach preset value: when not reaching preset value, then adjust (increase or reduce) treatment parameter by input/output signal control card 22 control steep-sided pulse control units 19, and get back to waveform acquisition and display routine, carry out parameter measurement and comparison once more, repeat this process and equate with preset value until measured value of parameters; When the parameter measured value equates with preset value, then pick up counting, in this process, waveform acquisition and display routine all start always.Treatment time and its preset value are compared: when treatment time did not reach preset value, then timing was proceeded, and continued relatively treatment time and its preset value; When treatment time reaches preset value, then export steep-sided pulses to installing inner fictitious load by input/output signal control card 22 control steep-sided pulse generating units 18, and " treatment " display lamp on the bench board 2 is extinguished by input/output signal control card 22 output control signals, expression " treatment " end.
(4) treatment finishes
Finishing in (3)-2. step is after " treatment " display lamp on the bench board 2 extinguishes, to extract electrode tip from cell suspension, the treatment end.
Therapeutic effect: the electron scanning micrograph of matched group (without treating steep pulse) and treating steep pulse group is respectively as Figure 14 and (all amplifying 4000 times) shown in Figure 15.By this figure as can be seen, cellular control unit film surface is complete, and in the processed group cell occur diameter be about 5 μ m hole (hole diameter that electroporation causes is generally 20～110nm), membranolysis, Cytoplasm sprays outward.Explanation is under the steep-sided pulse effect, and violent metamorphosis process has taken place cell membrane.Can infer that this is the result that the steep-sided pulse cell membrane causes the irreversibility electrical breakdown.
Embodiment 3:
As shown in Figure 6, a kind for the treatment of steep pulse subcutaneous transplantation human cervical carcinoma U
14The method of BALB/c mouse, utilize " bundling electrode with integrated positive pole and negative pole of shape memory alloy " of tumor treating steep pulse device of the present invention and the applicant's publication number for CN1810318A, by program to subcutaneous transplantation human cervical carcinoma U
14The BALB/c mouse concrete grammar step for the treatment of as follows:
(1) initialization
After the tumor treating steep pulse device start of the present invention, characteristic parameter of initialization steep-sided pulse (being peak value of pulse, repetition rate, pulse width, rise time and treatment time) and program parameter (as waveform acquisition, waveform demonstration, timing time etc.).
(2) determine the treatment parameter
1. formulate therapeutic scheme
(1) step finish after, according to subcutaneous transplantation human cervical carcinoma U
14The characteristics (2 months ages of Mus, body weight 35 to 38 grams, female) of BALB/c mouse and the concrete condition of tumor tissues (body, malignant tumor, diameter about 1cm, the position is below the mouse hind leg) formulate the corresponding treatment scheme, the characteristic parameter of determining steep-sided pulse is: peak value of pulse 40V, repetition rate 50Hz, pulse width 30 μ s, rise time 100ns, treatment time 30min, it is dark that 1cm is inserted on the tumor tissues surface of the vertical mouse hind leg of electrode tip below.
2. preset the treatment parameter
According to definite treatment parameter of (2)-1. step, by the computer system 32 of apparatus of the present invention, the peak value of pulse that presets the tumor treating steep pulse device is that 40V, repetition rate are that 50Hz, pulse width are 30 μ s, rise time to be that 100ns, treatment time are 30min.
(3) treat
1. insert electrode tip
After finishing in (2) step, the on position and the degree of depth of the electrode tip of determining according to (2)-1. step are inserted electrode tip in the tumor tissues of treatment.
2. treat
(3)-1. the step finish after, enter the KeyEvent determining program: when judged result is " preparation ", then export steep-sided pulses to installing inner fictitious load by input/output signal control card 22 control steep-sided pulse generating units 18, and making " preparation " display lamp on the bench board 2 bright by input/output signal control card 22 output control signals, expression can enter " treatment "; When judged result is " treatment ", then organize by 11 output steep-sided pulse to the external tumor of the steep-sided pulse out splice going splice on the bench board 2 by input/output signal control card 22 control steep-sided pulse generating units 18, and " preparation " display lamp on the bench board 2 is extinguished by input/output signal control card 22 output control signals, " treatment " display lamp is bright, expression enters " treatment ", log-on data capture card 21 begins to gather the steep-sided pulse waveform simultaneously, the steep-sided pulse waveform is presented in real time on the screen of liquid crystal display 1, and measures each characteristic parameter (peak value of pulse of steep-sided pulse, repetition rate, pulse width and rise time).Each steep-sided pulse parameter that records and the parameter that preset are originally compared, judge whether to reach preset value: when not reaching preset value, then adjust (increase or reduce) treatment parameter by input/output signal control card 22 control steep-sided pulse control units 19, and get back to waveform acquisition and display routine, carry out parameter measurement and comparison once more, repeat this process and equate with preset value until measured value of parameters; When the parameter measured value equates with preset value, then pick up counting, in this process, waveform acquisition and display routine all start always.Treatment time and its preset value are compared: when treatment time did not reach preset value, then timing was proceeded, and continued relatively treatment time and its preset value; When treatment time reaches preset value, then export steep-sided pulses to installing inner fictitious load by input/output signal control card 22 control steep-sided pulse generating units 18, and " treatment " display lamp on the bench board 2 is extinguished by input/output signal control card 22 output control signals, expression " treatment " end.
(4) treatment finishes
Finishing in (3)-2. step is after " treatment " display lamp on the bench board 2 extinguishes, to extract electrode tip from tumor tissues, the treatment end.
Therapeutic effect: BALB/c mouse hind leg below subcutaneous transplantation human cervical carcinoma U
14, all posterior tuberosity body diameters can reach about 1cm, as shown in figure 16.At this moment, BALB/c mouse is carried out treating steep pulse; Set up matched group simultaneously, do not apply treating steep pulse.Treatment group and matched group are under equal conditions raised, and measure the tumor size of treatment group and matched group every other day, and calculate gross tumor volume according to formula (2):
V＝πabc/6(2)
In the formula, a, b, c are respectively the length and widths, thick of tumor.Treated back 3 days, treatment group mouse tumor body begins incrustation, as shown in figure 17; Control group mice tumor body then constantly increases.Treated back 10 days, treatment group mouse tumor body eschar comes off, the skin surface organization healing, as shown in figure 18; Control group mice tumor body then continues to increase, as shown in figure 19.Get the matched group mean tumour volume making tumor self-sow curve of every day, get the treatment group mean tumour volume making tumor suppression curve of every day, as shown in figure 20.As can be seen from Figure 20,5 days matched groups and treatment group tumor growth begin to occur difference behind the treating steep pulse, and the treatment group is suppressed; Along with the tumor-bearing mice life span prolongs, two groups of tumor growth rate difference increase gradually.Two groups of t assay P＜0.05, the two difference has significance.In 20 mices of treatment group, there are 9 incrustations to come off and healing fully, cure rate reaches 45%; And have 6 mices dead in 15 days in 20 mices of matched group, find that through dissecting malignant tumor extensively shifts in vivo.Treatment group and matched group are under equal conditions raised, the existence of giving free rein to, and record mouse diing time (is unit with the sky) is used the Kaplan-MeierShi method and is made the tumor-bearing mice survival curve, as shown in figure 21.As can be seen, tumor-bearing mice was grown preceding 15 days, the survival curve no significant difference of treatment group and matched group; After 15 days, the dead quantity of matched group tumor-bearing mice increases, and by the 60th day, control group mice was all dead, and the treatment group still has 9 existence, and two groups of differences have highly significant (P＜0.01).The matched group tumor-bearing mice mean survival time is 33.05 days, and the treatment group tumor-bearing mice mean survival time is 52.05 days.
Binding of pathological histological observation result and transmission electron microscope observation result, can draw as drawing a conclusion: the malignant cell behind the treating steep pulse is killed and wounded, the tumor growth of treatment group tumor-bearing mice is subjected to obvious inhibition, be significantly longer the life cycle of treatment group tumor-bearing mice, demonstrates good potential applicability in clinical practice.
Claims (7)
1, a kind of tumor treating steep pulse device, it is characterized in that mainly comprising that steep-sided pulse takes place and TT﹠C system (7), computer system (32), power-supply system (9) and bench board (2), wherein: steep-sided pulse generation and TT﹠C system (7) are by steep-sided pulse generating unit (18), steep-sided pulse control unit (19) and steep-sided pulse are measured pre-process unit (20) and are formed, steep-sided pulse control unit (19) is connected with lead with steep-sided pulse generating unit (18), steep-sided pulse generating unit (18) is measured pre-process unit (20) with steep-sided pulse and is connected with lead, computer system (32) is by industrial control computer main frame (8), liquid crystal display (1), keyboard and mouse (3), data collecting card (21) and input/output signal control card (22) are formed, liquid crystal display (1), keyboard and mouse (3) is connected with lead with industrial control computer main frame (8), data collecting card (21) is inserted in the bus slot of industrial control computer main frame (8), and measure pre-process unit (20) with steep-sided pulse and link to each other with coaxial cable (30), input/output signal control card (22) also is inserted in the bus slot of industrial control computer main frame (8), and link to each other with data wire (29) with steep-sided pulse control unit (19), power-supply system (9) is by isolating transformer (24), UPS (25), linear DC power supply (27) and wiring board (26) are formed, the civil power of input inserts isolating transformer (24) with lead earlier, the outfan of isolating transformer (24) is connected to UPS (25) with lead, the outfan of UPS (25) is connected to wiring board (26) with lead, the outfan of wiring board (26) is connected to linear DC power supply (27) with power line (31), steep-sided pulse takes place and TT﹠C system (7), industrial control computer main frame (8) and liquid crystal display (1), linear DC power supply (27) takes place to link to each other with power line (31) with TT﹠C system (7) with steep-sided pulse, bench board (2) is by on and off switch (12), display lamp (13) and steep-sided pulse out splice going splice (11) are formed, they all take place to link to each other with holding wire (28) with TT﹠C system (7) with steep-sided pulse, liquid crystal display (1) is installed in rack (4) top, bench board (2) is installed in rack (4) upper end, in rack (4), be equiped with keyboard and mouse (3) from top to bottom successively, steep-sided pulse takes place and TT﹠C system (7), industrial control computer main frame (8) and power-supply system (9), four jiaos of places, lower end at rack (4) are equiped with universal wheel (5), are equiped with handle (6) in the upper end of rack (4) back.
2, according to the described tumor treating steep pulse device of claim 1, it is characterized in that the steep-sided pulse that is produced is unidirectional exponential damping electric pulse, its peak value of pulse adjustable continuously between 0V～1000V, repetition rate adjustable continuously between 1Hz～10kHz, rise time adjustable continuously between 10ns～100ns, pulse width between 100ns～100 μ s, divide 6 grades adjustable.
3, according to the described tumor treating steep pulse device of claim 1, it is characterized in that a kind of tumor treating steep pulse device, comprise that mainly steep-sided pulse takes place and TT﹠C system (7), computer system (32), power-supply system (9) and bench board (2), wherein: steep-sided pulse generation and TT﹠C system (7) are by steep-sided pulse generating unit (18), steep-sided pulse control unit (19) and steep-sided pulse are measured pre-process unit (20) and are formed, steep-sided pulse control unit (19) is connected with lead with steep-sided pulse generating unit (18), steep-sided pulse generating unit (18) is measured pre-process unit (20) with steep-sided pulse and is connected with lead, steep-sided pulse generating unit (18) links to each other with power-supply system (9) with power line (31) with dc source interface (16) by AC power interface (17), steep-sided pulse control unit (19) links to each other with computer system (2) with data wire (29) by data line interface (15), link to each other with power-supply system (9) with power line (28) by dc source interface (16), steep-sided pulse is measured pre-process unit (20) and is linked to each other with computer system (2) with coaxial cable (30) by coaxial cable interface (14), link to each other with power-supply system (9) with power line (31) by dc source interface (16), computer system (32) is by industrial control computer main frame (8), liquid crystal display (1), keyboard and mouse (3), data collecting card (21) and input/output signal control card (22) are formed, liquid crystal display (1), keyboard and mouse (3) is connected with lead with industrial control computer main frame (8), data collecting card (21) is inserted in the bus slot of industrial control computer main frame (8), and measure pre-process unit (20) with steep-sided pulse and link to each other with coaxial cable (30), input/output signal control card (22) also is inserted in the bus slot of industrial control computer main frame (8), and link to each other with data wire (29) with steep-sided pulse control unit (19), power-supply system (9) is by isolating transformer (24), UPS (25), linear DC power supply (27) and wiring board (26) are formed, the civil power of input 220V/50Hz inserts isolating transformer (24) by alternating current power supply input interface (23) with lead, the outfan of isolating transformer (24) is connected to UPS (25) with lead, the outfan of UPS (25) is connected to wiring board (26) with lead, the outfan of wiring board (26) is connected to linear DC power supply (27) with power line (31), steep-sided pulse takes place and TT﹠C system (7), industrial control computer main frame (8) and liquid crystal display (1), linear DC power supply (27) takes place to link to each other with power line (31) with TT﹠C system (7) with steep-sided pulse, bench board (2) is by on and off switch (12), display lamp (13) and steep-sided pulse out splice going splice (11) are formed, they all take place to link to each other with holding wire (28) with TT﹠C system (7) with steep-sided pulse, liquid crystal display (1) is installed in rack (4) top, its inclination angle is according to the user's request flexible, bench board (2) is installed in rack (4) upper end on the inclined-plane of 22.5 degree angles, in rack (4), be equiped with keyboard and mouse (3) from top to bottom successively, steep-sided pulse takes place and TT﹠C system (7), industrial control computer main frame (8) and power-supply system (9), be provided with Qianmen and back door and two side doors around the rack (4), Qianmen and back door all are equiped with automatic locking, two side door structures are identical, all fix with four screws, be provided with the two rows air vent on it, four jiaos of places, lower end at rack (4) are equiped with universal wheel (5), are equiped with handle (6) in the upper end of rack (4) back.
4, according to the described tumor treating steep pulse device of claim 3, the circuit that it is characterized in that described steep-sided pulse generating unit (18) is mainly by the commercial power rectification filter circuit, forward converter, the impulse commutation filter circuit, sampling feedback circuit, capacitor charge and discharge circuit and steepness circuit are formed, diode D11, D12, D13 and D14 form rectification circuit, capacitor C 11 is formed filter circuit, high frequency transformer Tr1, insulated gate bipolar transistor IGBT K11 and fast recovery diode D15 constitute the forward converter circuit, high frequency transformer Tr1 comprises ferrite core and enamel-covered wire, its former limit links to each other with IGBT K11 with filter capacitor C11, secondary links to each other with simulation ground with fast recovery diode D15, the colelctor electrode of IGBTK11 links to each other with the former limit of high frequency transformer Tr1, emitter stage links to each other with filter capacitor C11, grid links to each other with steep-sided pulse control unit (19), the two ends of fast recovery diode D15 link to each other with filter inductance L1 with the secondary of high frequency transformer Tr1, the impulse commutation filter circuit is by fast recovery diode D16, filter inductance L1 and filter capacitor C12 form, the two ends of fast recovery diode D16 link to each other with simulation ground with fast recovery diode D15, the two ends of filter inductance L1 link to each other with filter capacitor C12 with fast recovery diode D15, the two ends of filter capacitor C12 link to each other with simulation ground with filter inductance L1, sampling feedback circuit is made up of resistance R 11 and adjustable resistance Rw1, the two ends of resistance R 11 link to each other with adjustable resistance Rw1 with filter capacitor C12, the two ends of adjustable resistance Rw1 link to each other with simulation ground with resistance R 11, and the intersection point of resistance R 11 and adjustable resistance Rw1 links to each other with steep-sided pulse control unit (19), capacitor charge and discharge circuit is by charging resistor R12, IGBT K12, IGBT K13 and capacitor group constitute, the two ends of charging resistor R12 link to each other with the colelctor electrode of resistance R 11 with IGBT K12, the colelctor electrode of IGBT K12 links to each other with charging resistor R12, emitter stage links to each other with the capacitor group, grid links to each other with steep-sided pulse control unit (19), the electric capacity that the capacitor group is intended ground by six common modes is formed, selecting one of them electric capacity by steep-sided pulse control unit (19) is mutual capacitance, link to each other with the emitter stage of IGBT K12 and the colelctor electrode of IGBT K13, the colelctor electrode of IGBTK13 links to each other with the capacitor group, emitter stage links to each other with capacitor C 13, grid links to each other with steep-sided pulse control unit (19), the steepness circuit is by capacitor C 13, steepness gap S1 and load are formed, the two ends of capacitor C 13 link to each other with simulation ground with the emitter stage of IGBT K13, the two ends of steepness gap S1 link to each other with load with capacitor C 13, and the two ends of load link to each other with simulation ground with steepness gap S1;
The pwm control circuit of described steep-sided pulse control unit (19) is a core with integrated circuit SG1525AJ IC21, one end of resistance R 21 links to each other with the intersection point of middle resistance R 11 of steep-sided pulse generating unit (18) and adjustable resistance Rw1, the other end links to each other with 1 foot of IC21, one end of resistance R 22 links to each other with the adjustable side of adjustable resistance Rw21, the other end links to each other with 2 feet of IC21, the end of adjustable resistance Rw21 links to each other with 16 feet of IC21, the other end links to each other with 1 Gnd1 digitally, the adjustable side links to each other with resistance R 22, the end of capacitor C t2 links to each other with 5 feet of IC21, the other end with digitally 1 link to each other, the end of resistance R t2 links to each other with 6 feet of IC21, the other end with digitally 1 link to each other, the end of resistance R d2 links to each other with 7 feet of IC21, the other end links to each other with 5 feet of IC21, one end of capacitor C 21 links to each other with 8 feet of IC21, the other end with digitally 1 link to each other, one end of capacitor C 22 links to each other with 9 feet of IC21, the other end links to each other with resistance R 23, one end of resistance R 23 links to each other with capacitor C 22, the other end links to each other with 1 foot of IC21,12 feet of IC21 with digitally 1 link to each other, 13 feet and 15 feet all link to each other with the power Vcc 1 of+15V;
The drive circuit of described steep-sided pulse control unit (19) is a core with integrated circuit TLP250 IC22, its output signal links to each other with the grid of three IGBT in the steep-sided pulse generating unit (18), 2 feet of IC22 link to each other with 11 feet or 14 feet in the pwm control circuit, one end of resistance R 24 links to each other with 3 feet of IC22, the other end with digitally 1 link to each other.5 feet of IC22 and 8 feet link to each other with the Vcc2 of the power supply Vee2 of-15V and+15V respectively, one end of resistance R 25 links to each other with 6 feet of IC22, the other end links to each other with 2 Gnd2 digitally, the end of adjustable resistance Rw22 links to each other with 6 feet of IC22, the adjustable side and the other end are the outfan of drive circuit, link to each other with the grid of three IGBT in the steep-sided pulse generating unit (18), the negative electrode of stabilivolt Z21 links to each other with the outfan of drive circuit, anode links to each other with the anode of stabilivolt Z22, the anode of stabilivolt Z22 links to each other with the anode of stabilivolt Z21, negative electrode with digitally 2 link to each other;
Described steep-sided pulse is measured the circuit of pre-process unit (20) by pulses of current sensor, current-voltage conversion circuit, amplifier stage and operating point servo circuit are formed, pulses of current sensor comprises annular crystallite magnetic core and enamel-covered wire, the pulsed current signal that steep-sided pulse generating unit (18) produces passes therethrough, its secondary links to each other with simulation ground with capacitor C 31, current-voltage conversion circuit is by integrated operational amplifier A31, resistance R 31 and R32 form, one end of resistance R 31 links to each other with the inverting input of A31, the other end links to each other with the outfan of A31, one end of resistance R 32 links to each other with the in-phase input end of A31, the other end links to each other with simulation ground, amplifier stage is by integrated operational amplifier A32, resistance R 33, R34 and R35 form, its output links to each other with the data collecting card (21) of computer system (2), one end of resistance R 33 links to each other with the outfan of A31, the other end links to each other with the inverting input of A32, one end of resistance R 34 links to each other with the inverting input of A32, the other end links to each other with the outfan of A32, one end of resistance R 35 links to each other with the in-phase input end of A32, the other end links to each other with simulation ground, the operating point servo circuit is by integrated operational amplifier A33, resistance R 36, R37, R38, capacitor C 32, C33 and diode D31, D32 forms, one end of resistance R 36 links to each other with the outfan of A32, the other end links to each other with the in-phase input end of A33, one end of capacitor C 32 links to each other with the in-phase input end of A33, the other end links to each other with simulation ground, the anode of diode D31 links to each other with the in-phase input end of A33, negative electrode links to each other with simulation ground, the negative electrode of diode D31 links to each other with the in-phase input end of A33, anode links to each other with simulation ground, one end of resistance R 37 links to each other with the inverting input of A33, the other end links to each other with simulation ground, one end of capacitor C 33 links to each other with the inverting input of A33, the other end links to each other with the outfan of A33, one end of resistance R 38 links to each other with the outfan of A33, and the other end links to each other with the in-phase input end of A31.
5, a kind of method of tumor treating steep pulse is utilized tumor treating steep pulse device of the present invention, utilizes the oncotherapy electrode, treats by program, it is characterized in that the concrete grammar step is as follows:
(1) initialization
After the tumor treating steep pulse device of the present invention start, the peak value of pulse of initialization steep-sided pulse, repetition rate, pulse width, rise time and treatment time characteristic parameter and program parameter;
(2) determine the treatment parameter
1. formulate therapeutic scheme
(1) step was formulated the corresponding treatment scheme according to patient's the characteristics and the concrete condition of tumor tissues thereof after finishing, and the on position of the characteristic parameter of definite steep-sided pulse and electrode tip and the degree of depth;
2. preset the treatment parameter
Treatment parameter according to (2)-1. step was determined by the computer system (32) of apparatus of the present invention, presets peak value of pulse, repetition rate, pulse width, rise time and the treatment time treatment parameter of tumor treating steep pulse device;
(3) treat
1. insert electrode tip
After finishing in (2) step, the on position and the degree of depth of the electrode tip of determining according to (2)-1. step are inserted electrode tip in the tumor tissues of treatment;
2. treat
(3)-1. the step finish after, enter the KeyEvent determining program: when judged result is " preparation ", then export steep-sided pulse to installing inner fictitious load by input/output signal control card (22) control steep-sided pulse generating unit (18), and making " preparation " display lamp on the bench board (2) bright by input/output signal control card (22) output control signal, expression can enter " treatment "; When judged result is " treatment ", then organize by the output of the steep-sided pulse out splice going splice (11) on the bench board (2) steep-sided pulse to external tumor by input/output signal control card (22) control steep-sided pulse generating unit (18), and " preparation " display lamp on the bench board (2) is extinguished by input/output signal control card (22) output control signal, " treatment " display lamp is bright, expression enters " treatment ", log-on data capture card (21) begins to gather the steep-sided pulse waveform simultaneously, the steep-sided pulse waveform is presented in real time on the screen of liquid crystal display (1), and measure the peak value of pulse of steep-sided pulse, repetition rate, pulse width and rise time characteristic parameter, each steep-sided pulse parameter that records and the parameter that preset are originally compared, judge whether to reach preset value: when not reaching preset value, then adjust the treatment parameter by input/output signal control card (22) control steep-sided pulse control unit (19), and get back to waveform acquisition and display routine, carry out parameter measurement and comparison once more, repeat this process and equate with preset value until measured value of parameters; When the parameter measured value equates with preset value, then pick up counting, in this process, waveform acquisition and display routine all start always, treatment time and its preset value are compared: when treatment time does not reach preset value, then timing is proceeded, and continues relatively treatment time and its preset value; When treatment time reaches preset value, then export steep-sided pulse to installing inner fictitious load by input/output signal control card (22) control steep-sided pulse generating unit (18), and " treatment " display lamp on the bench board (2) is extinguished by input/output signal control card (19) output control signal, expression " treatment " end;
(4) treatment finishes
Finishing in (3)-2. step is after " treatment " display lamp on the bench board (2) extinguishes, to extract electrode tip from tumor tissues, the treatment end.
6,, it is characterized in that a kind for the treatment of steep pulse people's ovary SKOV that exsomatizes according to the method for the described tumor treating steep pulse of claim 5
3The method of cancerous cell is utilized " bundling electrode with integrated positive pole and negative pole of shape memory alloy " of tumor treating steep pulse device of the present invention and the applicant's publication number for CN 1810318A, by program to people's ovary SKOV
3The concrete grammar step that cancerous cell is treated is as follows:
(1) initialization
After the tumor treating steep pulse device of the present invention start, the peak value of pulse of initialization steep-sided pulse, repetition rate, pulse width, rise time and treatment time characteristic parameter and program parameter;
(2) determine the treatment parameter
1. formulate therapeutic scheme
(1) step finish after, according to people's ovary SKOV
3The characteristics of cancerous cell, promptly exsomatize, malignant tumor, cell suspension, formulate therapeutic scheme, the characteristic parameter of determining steep-sided pulse is: peak value of pulse 200V, repetition rate 100Hz, pulse width 10 μ s, rise time 100ns, treatment time 20min, and it is dark that 1cm is inserted on the vertical cell suspension of electrode tip surface;
2. preset the treatment parameter
According to definite treatment parameter of (2)-1. step, by the computer system (32) of apparatus of the present invention, the peak value of pulse that presets the tumor treating steep pulse device is that 200V, repetition rate are that 100Hz, pulse width are 10 μ s, rise time to be that 100ns, treatment time are 20min;
(3) treat
1. insert electrode tip
After finishing in (2) step, the on position and the degree of depth of the electrode tip of determining according to (2)-1. step are inserted electrode tip stripped people's ovary SKOV of treatment
3In the cancerous cell suspension;
2. treat
(3)-1. the step finish after, enter the KeyEvent determining program: when judged result is " preparation ", then export steep-sided pulse to installing inner fictitious load by input/output signal control card (22) control steep-sided pulse generating unit (18), and making " preparation " display lamp on the bench board (2) bright by input/output signal control card (22) output control signal, expression can enter " treatment "; When judged result is " treatment ", then export steep-sided pulse to external tumor cell suspension by the steep-sided pulse out splice going splice (11) on the bench board (2) by input/output signal control card (22) control steep-sided pulse generating unit (18), and " preparation " display lamp on the bench board (2) is extinguished by input/output signal control card (22) output control signal, " treatment " display lamp is bright, expression enters " treatment ", log-on data capture card (21) begins to gather the steep-sided pulse waveform simultaneously, the steep-sided pulse waveform is presented in real time on the screen of liquid crystal display (1), and measure the peak value of pulse of steep-sided pulse, repetition rate, pulse width and rise time characteristic parameter, each steep-sided pulse parameter that records and the parameter that preset are originally compared, judge whether to reach preset value: when not reaching preset value, then adjust the treatment parameter by input/output signal control card (22) control steep-sided pulse control unit (19), and get back to waveform acquisition and display routine, carry out parameter measurement and comparison once more, repeat this process and equate with preset value until measured value of parameters; When the parameter measured value equates with preset value, then pick up counting, in this process, waveform acquisition and display routine all start always, treatment time and its preset value are compared: when treatment time does not reach preset value, then timing is proceeded, and continues relatively treatment time and its preset value; When treatment time reaches preset value, then export steep-sided pulse to installing inner fictitious load by input/output signal control card (22) control steep-sided pulse generating unit (18), and " treatment " display lamp on the bench board (2) is extinguished by input/output signal control card (22) output control signal, expression " treatment " end;
(4) treatment finishes
Finishing in (3)-2. step is after " treatment " display lamp on the bench board (2) extinguishes, to extract electrode tip from cell suspension, the treatment end.
7,, it is characterized in that a kind for the treatment of steep pulse subcutaneous transplantation human cervical carcinoma U according to the method for the described tumor treating steep pulse of claim 5
14The method of BALB/c mouse, utilize " bundling electrode with integrated positive pole and negative pole of shape memory alloy " of tumor treating steep pulse device of the present invention and the applicant's publication number for CN 1810318A, by program to subcutaneous transplantation human cervical carcinoma U
14The BALB/c mouse concrete grammar step for the treatment of as follows:
(1) initialization
After the tumor treating steep pulse device of the present invention start, the peak value of pulse of initialization steep-sided pulse, repetition rate, pulse width, rise time and treatment time characteristic parameter and program parameter;
(2) determine the treatment parameter
1. formulate therapeutic scheme
(1) step finish after, according to subcutaneous transplantation human cervical carcinoma U
14The characteristics of BALB/c mouse, be 2 months ages of Mus, body weight 35 to 38 grams, female, and the concrete condition of tumor tissues, promptly body, malignant tumor, diameter about 1cm, the position is below the mouse hind leg, formulate the corresponding treatment scheme, the characteristic parameter of determining steep-sided pulse is: peak value of pulse 40V, repetition rate 50Hz, pulse width 30 μ s, rise time 100ns, treatment time 30min, and it is dark that 1cm is inserted on the tumor tissues surface of the vertical mouse hind leg of electrode tip below;
2. preset the treatment parameter
According to definite treatment parameter of (2)-1. step, by the computer system (32) of apparatus of the present invention, the peak value of pulse that presets the tumor treating steep pulse device is that 40V, repetition rate are that 50Hz, pulse width are 30 μ s, rise time to be that 100ns, treatment time are 30min;
(3) treat
1. insert electrode tip
After finishing in (2) step, the on position and the degree of depth of the electrode tip of determining according to (2)-1. step are inserted electrode tip in the tumor tissues of treatment;
2. treat
(3)-1. the step finish after, enter the KeyEvent determining program: when judged result is " preparation ", then export steep-sided pulse to installing inner fictitious load by input/output signal control card (22) control steep-sided pulse generating unit (18), and making " preparation " display lamp on the bench board (2) bright by input/output signal control card (22) output control signal, expression can enter " treatment "; When judged result is " treatment ", then organize by the output of the steep-sided pulse out splice going splice (11) on the bench board (2) steep-sided pulse to external tumor by input/output signal control card (22) control steep-sided pulse generating unit (18), and " preparation " display lamp on the bench board (2) is extinguished by input/output signal control card (22) output control signal, " treatment " display lamp is bright, expression enters " treatment ", log-on data capture card (21) begins to gather the steep-sided pulse waveform simultaneously, the steep-sided pulse waveform is presented in real time on the screen of liquid crystal display (1), and measure the steep-sided pulse peak value of pulse, repetition rate, pulse width and rise time characteristic parameter, each steep-sided pulse parameter that records and the parameter that preset are originally compared, judge whether to reach preset value: when not reaching preset value, then adjust the treatment parameter by input/output signal control card (22) control steep-sided pulse control unit (19), and get back to waveform acquisition and display routine, carry out parameter measurement and comparison once more, repeat this process and equate with preset value until measured value of parameters; When the parameter measured value equates with preset value, then pick up counting, in this process, waveform acquisition and display routine all start always, treatment time and its preset value are compared: when treatment time does not reach preset value, then timing is proceeded, and continues relatively treatment time and its preset value; When treatment time reaches preset value, then export steep-sided pulse to installing inner fictitious load by input/output signal control card (22) control steep-sided pulse generating unit (18), and " treatment " display lamp on the bench board (2) is extinguished by input/output signal control card (22) output control signal, expression " treatment " end;
(4) treatment finishes
Finishing in (3)-2. step is after " treatment " display lamp on the bench board (2) extinguishes, to extract electrode tip from tumor tissues, the treatment end.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102500060A (en) * | 2011-12-02 | 2012-06-20 | 李开华 | Intelligent electrochemical tumor treating system |
| CN105055015A (en) * | 2015-08-05 | 2015-11-18 | 天津市鹰泰利安康医疗科技有限责任公司 | Irreversible electroporation system |
| CN106943190A (en) * | 2017-04-25 | 2017-07-14 | 天津市鹰泰利安康医疗科技有限责任公司 | A kind of two-way steep-sided pulse system of tumor treatment |
| CN109124759A (en) * | 2018-09-12 | 2019-01-04 | 上海睿刀医疗科技有限公司 | Cooperate with generation method, device, medium and the electronic equipment of electric impulse signal |
| CN111751264A (en) * | 2019-03-26 | 2020-10-09 | 上海电力学院 | Form on-line monitoring device of electric breakdown cell |
| CN116509534A (en) * | 2023-03-13 | 2023-08-01 | 浙江伽奈维医疗科技有限公司 | IGBT current detection and control device, system and method for steep pulse therapy |
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| CN101972168B (en) * | 2010-11-16 | 2012-05-02 | 重庆大学 | Device for treating tumors through irreversible electroporation |
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- 2007-03-13 CN CNB2007100782827A patent/CN100469331C/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102500060A (en) * | 2011-12-02 | 2012-06-20 | 李开华 | Intelligent electrochemical tumor treating system |
| CN105055015A (en) * | 2015-08-05 | 2015-11-18 | 天津市鹰泰利安康医疗科技有限责任公司 | Irreversible electroporation system |
| CN106943190A (en) * | 2017-04-25 | 2017-07-14 | 天津市鹰泰利安康医疗科技有限责任公司 | A kind of two-way steep-sided pulse system of tumor treatment |
| CN106943190B (en) * | 2017-04-25 | 2023-09-12 | 天津市鹰泰利安康医疗科技有限责任公司 | Bidirectional steep pulse tumor treatment system |
| CN109124759A (en) * | 2018-09-12 | 2019-01-04 | 上海睿刀医疗科技有限公司 | Cooperate with generation method, device, medium and the electronic equipment of electric impulse signal |
| CN109124759B (en) * | 2018-09-12 | 2019-12-31 | 上海睿刀医疗科技有限公司 | Method, device, medium, and electronic device for generating coordinated electric pulse signal |
| CN111751264A (en) * | 2019-03-26 | 2020-10-09 | 上海电力学院 | Form on-line monitoring device of electric breakdown cell |
| CN116509534A (en) * | 2023-03-13 | 2023-08-01 | 浙江伽奈维医疗科技有限公司 | IGBT current detection and control device, system and method for steep pulse therapy |
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