WO2008090444A1

WO2008090444A1 - Device for generating voltage pulses that can be controlled by means of solid-state switch devices and can be applied to the human body

Info

Publication number: WO2008090444A1
Application number: PCT/IB2008/000142
Authority: WO
Inventors: Claudio Bertacchini; Pier Mauro Margotti
Original assignee: Igea S.R.L.
Priority date: 2007-01-23
Filing date: 2008-01-23
Publication date: 2008-07-31
Also published as: ITTO20070044A1

Abstract

A device for generating voltage pulses that can be controlled by means of solid-state switch devices and can be applied to the human body, said device being of the type comprising: a driver (12) designed to generate a driving signal; at least one solid-state electronic switch (13) actuated in switching by the driving signal for partializing a d.c. voltage (Vcc) and generating voltage pulses supplied to electrodes (18a, 18b) that can be applied to a biological tissue (19) in which a pulsating electro-magnetic field is generated. Also provided is a closed-loop control circuit (20, 22, 32, 33) designed to reduce the amplitude of the driving signal applied to a control terminal (13g) of the solid-state electronic switch (13) when the value of the current supplied to the electrodes approaches a threshold value indicating a potentially critical condition of operation (Figure 2) whilst the driving- signal modalities of the device typical of existing drivers are preserved. There may be provided a control circuit for controlling the duration of the pulses (40, 41, 42).

Description

DEVICE FOR GENERATING VOLTAGE PULSES THAT CAN BE CONTROLLED BY MEANS OF SOLID-STATE SWITCH DEVICES AND CAN BE APPLIED TO THE HUMAN BODY

TECHNICAL FIELD

The present invention relates to a device for generating voltage pulses that can be controlled by solid-state switch devices and can be applied to the human body.

BACKGROUND ART

It is known to apply voltage pulses to the human body in order to obtain a pulsating electrical field that produces therapeutic effects in the tissues irradiated.

For example, the treatment of electroporation consists in applying to the tissues voltage pulses having an amplitude such as to obtain an electrical field that determines an alteration of the cell membranes, opening the pores thereof in an above normal way. The alteration of the cell membrane is thus used to carry, within the cell, chemical substances (for example, drugs) and/or organic matter (for example, proteins, portions of DNA, etc.) .

Typically, electroporation methods are implemented using a generator of a train of voltage pulses that is connected at output to conductive electrodes applied to the tissue.

Generation of the pulse train is normally obtained using solid-state switch devices (e.g., IGBTs or MOSFETs), which partialize a d.c. voltage obtained by means of a voltage generator, for example constituted by a battery of capacitors.

Solid-state switch devices enable very precise control over time of the electrical connection between the electrodes and the voltage generator; however, they are intrinsically sensitive to: - overvoltages that can arise across the junction and that can irreversibly perforate it; and

- excessive dissipation of energy in the junction itself, which can determine melting of the silicon and hence again irreversible damage.

Furthermore, when the treatment of electroporation requires application of high voltages (500 V can be assumed as reference threshold) , the likelihood of there being sparks at the electrodes is rather high for the following reasons:

- the very nature of the tissues that are intrinsically non homogeneous and have a conductivity that can vary in time and space (the conductivity depends in fact upon the degree of hydration and upon the type of tissue and can vary according to the voltage applied) ;

- the variability of the interface of contact between the electrodes and the tissue in so far as, in a region corresponding to the interface, processes of electrolysis can be set up with formation of bubbles of gas (hydrogen) that modify the conductivity of the interface; and

- human factors: the electrodes can imperceptibly be brought into mutual contact or be set excessively close to one another .

In the absence of appropriate precautions, the consequences of a spark or of a short-circuit can be very serious, both because they can determine the failure of the solid-state switch device used and because they can determine damage to the tissues and possible complications in the post-treatment period. In particular, if protective measures are not adopted, the failure of the solid-state switch device can determine serious damage to the tissue in so far as the mode of failure of the junction is frequently a short-circuit that determines an irreversible and direct connection between the voltage generator and the tissue, and consequently a dissipation of energy in the tissue that is limited only by the power that the voltage generator is able to supply.

In order to overcome the drawbacks set forth above, protection devices have been devised designed to detect a condition of overcurrent (due, for example, to a short-circuit or spark) and automatically interrupt generation of the voltage pulses.

An example of a protection device of a known type is illustrated in Figure 1, where a control device 1 drives a driver 2 which, in turn, drives the control terminal (gate) of a solid-state switch 3, in this case constituted by an IGBT.

The driver 2 is able to detect the short-circuit condition, or in any case an overcurrent, and automatically interrupt supply of the control pulse to the IGBT 3.

In greater detail, the driver 2 detects the voltage difference Vce between the collector and the emitter of the IGBT 3 by means of a diode 4, and, when the voltage difference Vce exceeds a given threshold, a condition in which the IGBT works in a linear way, i.e., it does not work in a condition of saturation, is detected.

The driver 2 thus enables the IGBT 3 to work in conditions of non-saturation for a pre-determined time, i.e., for the time necessary for the IGBT 3 to reach the condition of saturation in which the IGBT behaves like a switch.

Hence, the configuration highlighted above does not enable limitation of the current that is supplied to the load during the time referred to above, and consequently during this time a considerable power is dissipated in the junction of the IGBT, equal to Vce multiplied by the current absorbed by the load.

Consequently, in the case where the short-circuit occurs in conditions of linear operation described above, even though there is envisaged an automatic opening of the IGBT, a considerable power is in any case dissipated within the electronic switch before complete opening of the switch itself takes place. Furthermore, the sudden interruption of the current can determine an overvoltage across the junction on account of the inductance associated to the load. The drivers consequently implement a "soft" turning-off modality precisely to minimize the probability of this occurring.

In the direct experience of the present applicant, protection devices of a known type, for example of the type illustrated in Figure 1, are not always sufficient to prevent failure of the solid-state device in the case of short-circuit and/or sparks.

It is thus mandatory to use solid-state switches capable of withstanding large currents (hundreds of amps) ; said switches are, however, very costly.

Amongst other things, in said applications, to protect the solid-state switch, it is not possible to use a protective fuse since normal fuses have excessively high response times for large currents .

DISCLOSURE OF INVENTION

The aim of the present invention is to provide a device for generating voltage pulses that can be controlled by means of solid-state switch devices and can be applied to the human body, said device being provided with a protection device that will be able to overcome the drawbacks of known devices of Figure 1 and will enable implementation therein of protection functions without any need to use protection fuses.

The above aim is achieved by the present invention in so far as it relates to a device for generation of voltage pulses that can be controlled by means of solid-state switch devices and can be applied to the human body, said device being of the type comprising: a driver designed to generate a driving signal for a solid-state electronic switch; at least one solid-state electronic switch actuated in switching by said driving signal for partializing a d.c. voltage and generating voltage pulses supplied to electrodes that can be applied to a biological tissue in which a pulsating electrical field is generated; current-detecting means designed to detect the intensity of the current supplied to said electrodes; and closed- loop control means designed to control said solid-state electronic switch as a function of detected values of said current, said device being characterized in that said closed- loop control means are designed to modify the amplitude of the driving signal applied to a control terminal of said solid- state electronic switch when the value of said current approaches a threshold value indicating a potentially critical condition of operation.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be illustrated with particular reference to the attached drawings, which illustrate a preferred non- limiting embodiment thereof and in which:

• Figure 1 illustrates a device of a known type for generating voltage pulses,- and

• Figure 2 illustrates the simplified electrical diagram of a device, built according to the teachings of the present invention, for generating voltage pulses that can be controlled by means of solid-state switch devices and can be applied to the human body.

BEST MODE FOR CARRYING OUT THE INVENTION

With reference to Figure 2, designated as a whole by 10 is a device, built according to the invention, for generating voltage pulses that can be controlled by means of solid-state switch devices and can be applied to the human body. The device 10 comprises a driver 12 (of a known type) , which is designed to generate an adequate driving signal Pigbt (for example, a square-wave voltage signal that varies in the driving-voltage range which is characteristic of the switch used) for the control terminal 13g (gate) of a solid-state electronic switch 13 which, in the example of embodiment illustrated, is obtained by means of an IGBT.

In particular, the IGBT 13 has a collector (c) to which a voltage Vcc produced by a voltage generator 15 (for example, formed by a bank of capacitors) is applied, and an emitter (e) that communicates through a shunt resistor 17 with at least one first electrode 18a applied to a portion of human or animal tissue (represented as a load resistor 19) . Moreover present is at least one second electrode 18b applied to the portion of human tissue and connected to the reference potential (ground) of the voltage generator 15.

The device 10 is moreover insulated from ground to guarantee the safety of the patient.

In this way, when the IGBT 13 is closed, the voltage Vcc is applied between the electrodes 18a, 18b, whilst when the transistor 13 is open, no voltage is applied between the electrodes 18a, 18b. In this way, by driving switching of the IGBT 13, voltage pulses applied to the electrodes 18a, 18b are generated, which produce a pulsating electrical field that involves the portion of human and/or animal tissue.

When the IGBT 13 is closed, a load current Ic flows in the tissue between the electrodes 18a, 18b causing on the shunt resistor 17 a voltage drop Vc=Ic-Rs (where Rs is the resistance of the shunt resistor 17) , proportional to the value of the current Ic measured. The voltage Vc is applied to a voltage-circuit decoupler 20 (of a known type) , which supplies the voltage Vc to an inverting input (-) of an operational amplifier 22 through a resistor 24 having a resistance Rl. The inverting input (-) of the operational amplifier 22 is connected to the output of the amplifier 22 itself through a resistor 26 having a resistance R2. Applied to the non-inverting input (+) of the operational amplifier 22 is a reference voltage Vr, which, in the schematic representation, is taken from a central terminal of a potentiometric trimmer 28 set in parallel to a reference- voltage generator 29 (represented schematically by a resistor and a Zener diode set in series to one another) , set between the voltage Vcc and the reference potential .

The output of the operational amplifier 22 supplies a control terminal (gate) of a first electronic switch 32 (N-MOSFET) , which is set between the output of the driver 12 and the control terminal (gate) of the IGBT 13.

The control terminal (gate) of the IGBT 13 is moreover connected to a first terminal of a second electronic switch 33 (P-MOSFET) having a second terminal connected to the reference voltage .

The output of the operational amplifier 22 is moreover connected to the cathode of a Zener diode 31 having an anode connected to the terminal 13g. A Schottky diode 35 is set between the drain of the N-MOSFET 32 and the gate 13g.

In this way, the two MOSFETs 32 and 33 have the gates and the sources in common. The drain of the N-MOSFET 32 receives the signal Pigbt, whilst the drain of the P-MOSFET 33 is connected to the negative potential of the supply.

The gates of the two MOSFETs 32 and 33 are connected to the output of the amplifier 22, whilst the Zener diode 31 is connected between the sources and gates with the cathode facing the gates. In turn, the Schottky diode 35 has its anode connected to the sources of the two MOSFETs 32 and 33 and its cathode that receives the signal Pigbt . The amplifier 22, together with the resistors 24 and 26, constitutes a stage for correction of the reference signal, whilst the two MOSFETs 32 and 33, together with the Zener diode 31 and the Schottky diode 35, constitute an amplifier stage that in normal conditions sends on the gate 13g of the IGBT 13 the signal of the driver leaving it as far as possible unaltered, whilst in the case of excessive current on the load 19 (indicating a potentially critical condition of operation) supplies to the gate 13g an appropriate signal, lower than the signal of the driver, which has the effect of limiting the current that flows in the IGBT 13, sending it out of saturation.

In use, in normal conditions of operation, the driver 12 generates the driving signal Pigbt, which is applied to the control terminal 13g of the IGBT through the first electronic switch 32, which is kept closed. In said conditions, in fact, the current Ic does not assume a high value (for example, it is comprised in the range of current typical of the IGBT or of the MOS used and is in any case lower than a threshold value) and consequently also the voltage Vc assumes a lower value, in particular much lower than the voltage Vr, i.e., Vr >> Vc.

In said condition, the output of the operational amplifier 22 assumes a positive saturation value, consequently keeping the first N-MOSFET 32 completely closed. The second P-MOSFET 33 is kept completely open in so far as a positive voltage is applied between its gate and its source.

In potentially critical conditions of operation, i.e., following upon an anomalous increase in the current on the load 19, the current Ic approaches a threshold value and also the voltage Vc increases, approaching the voltage Vr. In said conditions of operation, the operational amplifier 22 amplifies the signal at input, and the voltage at its output Vout assumes a value dictated by the known law:

Vout = Vr + (Vr -Vc) • (R2/R1) i.e. ,

Vout = Vr + (Vr - Rs-Ic) • (R2/R1)

In such conditions, the channel resistance of the first electronic switch 32 (N-MOSFET) increases, limiting the current that the second switch 33 absorbs from the driver. At the same time, the channel resistance of the second switch 33

(P-MOSFET) decreases. The second switch 33 thus increases its current and absorbs charges from the gate of the solid-state device 13, reducing the conductivity thereof, and thus carrying out, in closed loop, a reduction of the current Ic.

In other words, in the condition highlighted above, the pair of MOS transistors 32 and 33 works in the linear region and each MOS behaves like an amplifier having a gain less than unity.

The reaction system thus reacts to the increase in current, reducing the driving signal in order to move away from a situation of risk.

Rs is sized so that in normal conditions the factor (V₁. - R₃Ic) is positive and is not close to zero. The ratio (R2/R1) , which constitutes a gain is chosen sufficiently large (R2/R1 > 10) in such a way that in normal conditions the output of the operational amplifier 22 saturates, and the signal detected on the shunt resistor 17 becomes of no effect.

When, instead, R_SI « V_r, then V_out determines the current carried by the IGBT 13.

In conditions of short-circuit or spark, the current Ic assumes a large value (for example, it can reach hundreds of amps and is in any case much higher than the threshold value) , and consequently also the voltage Vc assumes a large value,- in particular, it is much higher than the voltage Vr, i.e. , Vc >> Vr.

In said conditions, the driving stage of the IGBT seeks to limit the value of Ic in such a way that we have Vc « Vr or Vc > Vr.

As explained previously, in said condition, the output of the operational amplifier 22 assumes a value such as to cause a decrease in conductivity of the MOSFET 32 and an increase in that of the second electronic switch 33 (P-MOSFET) . Since the second transistor 33 is connected to the negative potential of the supply of the stage, current is drained away from the gate of the IGBT 13.

Consequently, the drop in the voltage on the gate 13g induces the IGBT 13 to exit from saturation, forcing tripping of the protection with which usually the driver 12 is equipped; i.e., the "soft" turning-off modality is triggered, which again the driver 12 usually activates in the case of de-saturation of the IGBT.

The device 10 is moreover provided with a control system designed to determine the temporal amplitude Tw of each voltage pulse supplied to the electrodes 18a, 18b in order to act on the driver 12 for disabling the driver 12 itself and terminating the pulse in the case where the temporal amplitude Tw exceeds a limit threshold value Tw-lim.

In this way, the maximum amplitude of each pulse is limited to the value Tw-lim irrespective of the driving signal generated by the driver 12, preventing the patient from being administered more energy than what is necessary. In particular, the control system 40 comprises a timer 41, which is activated by the passage of current Ic in the shunt resistor 17 (and hence by the rising edge FS of each voltage pulse detected by the current sensor 40) . The timer 41 thus controls the duration of the pulse. The output signal of the timer 41 enables the driver 12 continuously through a logic 42, thus enabling continuation of generation of the pulse.

In the case where the pulse is too long, the timer 41 goes into time-out, changing the state of its output and disabling through the logic 42 the driver 12, which thus interrupts the pulse.

Alternatively, the signal of the timer can be used for driving, through an appropriate driver, a second solid-state device (not illustrated) set in series to the switch 13. In this way, a redundancy is inserted, which protects both against the possibility of the signal applied to the electrodes 18a, 18b not being controlled correctly and against the possibility of failure by short-circuiting of the device 13.

The advantages of the invention are hence the following: - protection of the electronics of the equipment that uses said control system;

- protection of the patient from damage to tissues due to the energy that could be discharged in the case of failure,-

- possibility of using solid-state switches (IGBTs or MOS transistors) that are not oversized and are hence less costly;

- possibility of calibrating the tripping threshold of the system by modifying the shunt resistance and/or the amplification factor of the control system;

- by introducing an automatic timing system on the driving signal, possibility of interrupting the pulses after a predetermined time, using the system as an electronic fuse that acts on two potentially dangerous components: the duration and the intensity of the current ;

- in operation as electronic fuse, possibility of protecting of the system and the patient in the case where the firmware of the system, on account of disturbance, were no longer able to function correctly or else in the case where the protection of the solid-state device were insufficient to preserve it and hence were to fail by shorting.

Claims

1.- A device for generating voltage pulses that can be controlled by means of solid-state switch devices and can be applied to the human body, said device being of the type comprising:

- a driver (12) designed to generate a driving signal for a solid-state electronic switch (13) ;

- at least one solid-state electronic switch (13) actuated in switching by said driving signal for partializing a d.c. voltage (Vcc) and generating voltage pulses supplied to electrodes (18a, 18b) that can be applied to a biological tissue (19) in which a pulsating electrical field is generated; - current-detecting means (17) designed to detect the intensity of the current supplied to said electrodes (18a, 18b) ; and

- closed-loop control means (20, 22, 32, 33) designed to control said solid-state electronic switch (13) as a function of detected values of said current, said device being characterized in that said closed- loop control means (20, 22, 32, 33) are designed to modify the amplitude of the driving signal applied to a control terminal (13g) of said solid-state electronic switch (13) when the value of said current approaches a threshold value indicating a potentially critical condition of operation.

2.- The device according to Claim 1, wherein said closed- loop control means (20, 22, 32, 33) are configured for reducing the driving signal when the value of said current detected exceeds a threshold value and indicates an overcurrent condition.

3.- The device according to Claim 2, wherein said closed- loop control means (20, 22, 32, 33) are configured for draining said driving signal towards a reference potential upon detection of said overcurrent condition.

4.- The device according to any one of the preceding claims, wherein said closed-loop control means (20, 22, 32, 33) comprise :

- at least one operational amplifier (22) designed to receive at its inputs (+ ;-) a difference of potential that is a function of the value (Vc) of the current measured and of at least one reference voltage (Vr) ; said operational amplifier (22) operating in a markedly linear way in the potentially critical condition of operation and operating in saturation in ordinary conditions of operation; and

- voltage-controlled switch means (32, 33) controlled by said operational amplifier (22) and designed to send the driving signal to a control terminal of said solid-state electronic switch (13); said switch means reducing the amplitude of the driving signal as a function of the value assumed by the output (Vout) of the operational amplifier when operating in a markedly linear way.

5. - The device according to Claim 4 , wherein said switch means comprise :

- a first voltage-controlled solid-state electronic switch

(32) set between an output of said driver (12) and the control terminal of said solid-state electronic switch (13) and designed to send, when closed, said driving signal to said control terminal ; and

- a second voltage-controlled solid-state electronic switch

(33) set in series to said first voltage-controlled solid- state electronic switch (32) and connected to a reference potential ; said first and second voltage-controlled solid-state electronic switches (32, 33) having control inputs receiving the output signal of said operational amplifier and operating in a substantially linear way with gain lower than unity in said substantially critical condition of operation.

6.- The device according to any one of the preceding claims, wherein said closed-loop control means (20, 22, 32, 33) comprise :

- calculation means (22, 24, 26, 28, 29) for calculation of an output voltage Vout that can be represented as: Vout = A * Vr - f (i) where :

• Vr is a reference voltage;

• f (i) is an increasing function of the current supplied to said electrodes; and • A is a gain, greater than or equal to 1;

- voltage-controlled switch means (32, 33) controlled as a function of said output voltage Vout and designed to send the driving signal to a control terminal of said solid-state electronic switch (13); said voltage-controlled switch means (32, 33) being configured for:

• transferring integrally the driving signal to said control terminal (13g) when said term f (i) is much smaller than Vr; • imposing upon the control terminal (13g) a supply such as to determine turning-off of the solid-state electronic switch (13); when the term f (i) is much greater than Vr,- and

• regulating the transfer of the driving signal to said control terminal (13g) as a function of Vout when the term f (i) is close to Vr.

7.- The device according to Claim 1, wherein a control system (40) is provided, designed to determine the temporal amplitude (Tw) of each voltage pulse supplied to the electrodes (18a, 18b) in order to act on said driver (12) for disabling the driver (12) itself and terminating the pulse in the case where the temporal amplitude (Tw) exceeds a limit threshold value (Tw- lim) , thus limiting the maximum temporal amplitude of each pulse to the threshold value (Tw-lim) irrespective of the driving signal generated by the driver (12) .

8. - The device according to Claim 7, wherein the temporal limitation is applied by controlling a second solid-state switch device set between said solid-state switch (13) and at least one electrode (18a) .