Power unit for delivering coherent sinusoidal burst irreversible electroporation energy to biological tissue

Abstract

A power unit for supplying electrical energy to at least one electrode of an electronic device for delivering coherent sinusoidal burst irreversible electroporation energy, the power unit comprising at least one power module configured to generate an electrical signal (S) to energize one or more respective electrodes, the or each power module comprising: - a selection block configured to receive at least one square wave input signal, wherein the selection block is configured to continuously vary an electrical energy level associated with the electrical signal (S) based on the at least one square wave input signal, so as to provide a combined signal at an output of the selection block, wherein the combined signal comprises a square wave waveform; - a filtering and electrical isolation block configured to convert the combined signal into a sinusoidal wave signal and to filter the sinusoidal wave signal to generate the electrical signal (S), wherein the conversion and the filtering are electrically isolated from each other.

Description

Technical Field

[0001] The present invention generally relates to a power unit for supplying electrical energy to multiple electrodes of an electronic device.

[0002] In particular, the present invention relates to a power unit for supplying electrical energy to multiple electrodes of an electronic device for delivering coherent sinusoidal burst irreversible electroporation energy, wherein the power unit is configured to generate an electrical signal to energize each electrode. Background Technology

[0003] Tissue ablation is used in numerous medical procedures to treat patients. Ablation can be performed to remove unwanted tissue (such as diseased heart cells) or to denature it. Ablation can be achieved by delivering energy (such as electrical energy) through one or more electrodes, causing the tissue at the site of contact with the electrodes to die. Ablation procedures can be performed on patients with any arrhythmia such as atrial fibrillation (AF) by ablating tissue in the heart.

[0004] Radiofrequency ablation (RFA) is a medical procedure in which heat generated by intermediate-frequency alternating current (e.g., in the range of 350–500 kHz) is used to ablate a portion of the electrical conduction system of the heart, tumors, or other dysfunctional tissues.

[0005] Specifically, in this procedure, an energy delivery device (such as a probe with or without a needle) is inserted into the target tissue to destroy the target area of ​​the cardiac tissue by applying thermal energy. In fact, electro-induced thermal ablation (such as RFA) can be used to effectively and continuously ablate tissue sites locally when the energy delivery device is placed on the tissue surface. Although RFA can effectively ablate large amounts of target tissue, this technique has limitations. A frequently mentioned problem when using this procedure during cardiac ablation involves heat sinking, which is a process that includes blood flow, and the heat generated on the ablation element is carried away / dissipated by the cooler blood flow above the element. This heat dissipation effect can alter both the shape and maximum volume of the tissue being ablated.

[0006] Recently, pulsed electric fields (PEFs) have been used as an alternative to radiofrequency ablation (RFA) for ablation of heart or organ tissue. A pulsed electric field (PEF) refers to the application of an intermittent, high-intensity electric field over a short time period (microseconds or nanoseconds), resulting in electroporation of cells and tissues. Electroporation is the process by which an applied electric field (i.e., the PEF) causes pores to form in the cell membrane. The formation of these pores leads to permeabilization, which can be reversible or irreversible, depending on the parameters of the applied PEF.

[0007] In reversible electroporation, cells remain viable and are based on electrochemical therapy and gene electrotransfer. In contrast, with irreversible electroporation (IRE), cells and tissues become unable to survive due to the activation of a programmed cell death cascade.

[0008] IRE is an effective treatment for solid tumors. However, given the limitations of current thermal-based methods, IRE can also be used in cardiology, particularly for cardiac ablation.

[0009] When used to ablate cardiac tissue, irreversible electroporation (IRE) involves applying electrical pulses to the target tissue in the microsecond to millisecond range, which can cause non-thermally generated defects at the nanoscale in the cell membrane. These defects can disrupt the cell membrane homeostasis, leading to irreversible cell membrane permeability and ultimately cell necrosis, without raising the temperature of the tissue ablation zone.

[0010] Typical PEF parameters for induced IRE include 10-90 pulses, pulse lengths of microseconds or nanoseconds (typically 100 μs), frequencies of 1-10 Hz, and electric fields between 500 and 3000 V / cm. (See Elad Maor et al., “Pulsedelectric fields for cardiac ablation and beyond: A state-of-the-art review”, Heart Rhythm 2019; 16:1112-1120).

[0011] One challenge in designing PEF protocols is isolating the effects of the electric field on biological tissue. According to Joule's first law, which states that heating power is proportional to resistance and the square of the current, an electric field applied across tissue generates heat. To overcome this problem and to obtain only electroporation damage, most PEF protocols use low-frequency (1-10 Hz) ultrashort pulses (microseconds). This balances heating with the cooling effects of physiological heat conduction and convection, thus preventing a significant temperature rise.

[0012] IREs performed using monopolar electrical pulses have the drawback of causing strong muscle contractions. Therefore, the clinical application of IREs requires the administration of general anesthesia and neurotoxins to eliminate the discomfort caused by muscle contractions experienced during each pulse. However, receiving anesthetics is undesirable for patients and may discourage them from seeking electroporation-based therapies.

[0013] Electronic systems for delivering irreversible electroporation (IRE) energy to biological tissues are known in the art, wherein such electronic systems are configured to generate high-frequency, bipolar waveforms for reducing muscle contraction during electroporation-based therapies.

[0014] In particular, high-frequency IRE (H-FIRE) is a technique for non-thermal tissue ablation that eliminates the muscle contractions experienced during IRE treatments performed using monopolar electrical pulses. In fact, during H-FIRE at 250 kHz or 500 kHz, no visual or tactile signs of muscle contraction are visible. Therefore, H-FIRE can be performed clinically without the administration of anesthetics.

[0015] H-FIRE can involve applying a square wave electrical signal. For this purpose, it is known, for example, to use a square wave signal centered at 500 kHz.

[0016] However, rectangular waveforms contain signal components with various frequencies and amplitudes, which can have dangerous effects when IREs are used specifically to treat cardiac tissue. For example, a conventional IRE square wave signal has a 150Hz component with a voltage of around 6V, which poses a significant risk of cardiac stimulation.

[0017] The problem with square-wave pulsed electric fields is similar to that of ICDs (internal cardioverter defibrillators): these types of devices can cause severe cardiac tissue damage upon discharge. Using square-wave pulsed electric fields can lead to cardiac tissue damage outside the intended area. Therefore, sedation is required, and square-wave delivery must be synchronized with the R wave of the ECG.

[0018] Therefore, there remains a strong sense of need to provide irreversible electroporation (IRE)-based treatments for biological tissues (especially cardiac tissue) that avoid myocardial stimulation and do not require patient sedation. Furthermore, it is desirable to provide a power generator capable of producing a signal suitable for applying electroporation while ensuring patient safety. It is also desirable to ensure that the power generator used to produce such a signal can utilize electronic components of practical size and rating. Summary of the Invention

[0019] This disclosure provides an electronic device for delivering irreversible electroporation (IRE) energy, particularly coherent sinusoidal burst IRE, to biological tissues to be treated, especially cardiac tissue. The electronic device has structural and functional features that meet the aforementioned requirements and overcomes the shortcomings of prior art electronic systems described above for the same purpose. This disclosure is helpful for understanding the disclosure as a whole.

[0020] In particular, this disclosure provides a novel electronic device 100 for delivering coherent sinusoidal burst irreversible electroporation energy or IRE to a biological tissue 1 to be treated, especially cardiac tissue.

[0021] Electronic device 100 includes:

[0022] Multiple electrodes 3, which can be positioned on or near the biological tissue 1 to be treated; and

[0023] Power generator 2, which supplies electrical energy to each of the electrodes 3 of the plurality of electrodes.

[0024] One object of the present invention is to provide a power generator 2 configured to generate an electrical signal S to energize each of the electrodes 3.

[0025] In one or more embodiments, the electrical signal S is formed by alternating a first electrical signal S1 and a second electrical signal S2 over time; the first electrical signal S1 is supplied to the electrode 3 during a first time interval T1, and the second electrical signal S2 is supplied to the electrode during a second time interval T2 following the first time interval T1; the first electrical signal S1 is a continuous bipolar signal comprising two or more fundamental sine waves SB within the first time interval T1, each fundamental sine wave consisting of a positive half-wave and a negative half-wave; the second electrical signal S2 has an amplitude equal to zero within the second time interval T2.

[0026] The applicant has demonstrated that an electrical signal S, generated by alternating a first electrical signal S1 comprising two or more fundamental sine waves with a second electrical signal S2 having zero amplitude over time, does not produce myocardial stimulation. Therefore, in the first respect, sedation of the patient is unnecessary. In the second respect, energy delivery does not need to be synchronized with the cardiac R wave of the ECG.

[0027] This disclosure also provides a method for controlling a plurality of electrodes in an electronic device for delivering coherent sinusoidal burst irreversible electroporation energy according to claim 26, wherein the electronic device includes a plurality of electrodes 3 and a power generator 2. The method involves: generating an electrical signal S by the power generator 2 for supplying electrical energy to each of the electrodes 3 of the plurality of electrodes, the electrical signal S being formed by alternating a first electrical signal S1 and a second electrical signal S2 over time, the first electrical signal S1 being a continuous bipolar signal comprising two or more fundamental sine waves SB during a first time interval T1, each fundamental sine wave consisting of a positive half-wave and a negative half-wave, the second electrical signal S2 having an amplitude equal to zero during a second time interval T2 following the first time interval T1. The method further includes: supplying the first electrical signal S1 to the electrodes 3 of the plurality of electrodes during the first time interval T1; and supplying the second electrical signal S2 to the plurality of electrodes (3) during the second time interval (T2).

[0028] Another object of the present invention is to provide an electronic device 100 for delivering irreversible electroporation energy or IRE to a biological tissue 1 to be treated. The electronic device includes one or more electrodes 3 that can be positioned on or near the biological tissue 1 to be treated, and a power generator 2 for supplying electrical energy to the one or more electrodes 3; the power generator 2 is configured to generate an electrical signal S to energize the one or more electrodes 3.

[0029] The electrical signal S can be formed by alternating between a first electrical signal S1 and a second electrical signal S2 over time; the first electrical signal S1 is supplied to one or more electrodes 3 during a first time interval T1, and the second electrical signal S2 is supplied to one or more electrodes during a second time interval T2 following the first time interval T1; the first electrical signal S1 has a periodic waveform in the first time interval T1; and the second electrical signal S2 has an amplitude equal to zero in the second time interval T2.

[0030] Another object of the present invention is to provide a power generator 2 for delivering coherent sinusoidal burst irreversible electroporation energy or IRE to a biological tissue 1 to be treated. The power generator may include a single-control unit 200 and a power unit 201 for generating an electrical signal S, which is formed by alternating a first electrical signal S1 and a second electrical signal S2 over time; the power unit 201 includes a power module 202, which can be driven by the single-control unit 200 to generate the first electrical signal S1 during a first time interval T1 and the second electrical signal S2 during a second time interval T2 following the first time interval T1; the first electrical signal S1 is a continuous bipolar signal comprising two or more fundamental sine waves SB during the first time interval T1, each fundamental sine wave consisting of a positive half-wave and a negative half-wave; the second electrical signal S2 has an amplitude equal to zero during the second time interval T2.

[0031] According to an alternative example, a method for ablating biological tissue 1 is provided. The method involves steps using an electronic device 100 according to the invention for delivering coherent sinusoidal burst irreversible electroporation energy or IRE.

[0032] According to an alternative example, a method for treating a patient's pathology is provided. The method involves performing ablation of the patient's biological tissue 1 using an electronic device 100 according to the invention for delivering coherent sinusoidal burst irreversible electroporation energy or IRE.

[0033] According to an alternative example, a method is provided for ablating biological tissue 1 by delivering irreversible electroporation energy or IRE. The method involves applying an electrical signal S comprising at least a sinusoidal signal to the biological tissue 1.

[0034] According to a preferred embodiment, the electrical signal S is formed by alternating between a first electrical signal S1 and a second electrical signal S2 over time; the first electrical signal S1 is applied during a first time interval T1, and the second electrical signal S2 is applied during a second time interval T2 following the first time interval T1; the first electrical signal S1 is a continuous bipolar signal comprising two or more fundamental sine waves SB within the first time interval T1, each fundamental sine wave consisting of a positive half-wave and a negative half-wave; the second electrical signal S2 has an amplitude equal to zero within the second time interval T2, thereby causing ablation of the biological tissue 1.

[0035] According to another preferred embodiment, the first electrical signal S1 has a frequency in the range of 25-49 kHz or in the range of 40-60 kHz.

[0036] According to an alternative example, a method is provided for treating a patient's pathology by delivering irreversible electroporation energy or IRE. The method includes the step of applying an electrical signal S to the patient's biological tissue 1, the electrical signal S being formed by alternating a first electrical signal S1 and a second electrical signal S2 over time; the first electrical signal S1 is applied during a first time interval T1, and the second electrical signal S2 is applied during a second time interval T2 following the first time interval T1; the first electrical signal S1 is a continuous bipolar signal comprising two or more fundamental sine waves SB within the first time interval T1, each fundamental sine wave consisting of a positive half-wave and a negative half-wave; the second electrical signal S2 has an amplitude equal to zero within the second time interval T2, thereby causing ablation of the biological tissue 1.

[0037] According to a preferred embodiment, the first electrical signal S1 has a frequency in the range of 25-49 kHz or in the range of 40-60 kHz.

[0038] Some advantageous embodiments are the subject of the dependent claims.

[0039] According to a first aspect of this disclosure, a power unit is provided for supplying electrical power to at least one electrode of an electronic device for delivering coherent sinusoidal burst irreversible electroporation energy, the power unit comprising at least one power module configured to generate an electrical signal (S) to energize one or more corresponding electrodes, said or each power module comprising: a selection block configured to receive at least one square wave input signal, wherein the selection block is configured to continuously change the power level associated with the electrical signal (S) based on the at least one square wave input signal to provide a combined signal at the output of the selection block, wherein the combined signal comprises a square wave waveform; and a filtering and electrical isolation block configured to convert the combined signal into a sinusoidal signal and filter the sinusoidal signal to generate the electrical signal (S), wherein the conversion and the filtering are electrically isolated from each other.

[0040] The first aspect is particularly advantageous because it provides electrical isolation, at least between the selection block and the electrical signal (S). This electrical isolation provides enhanced safety for patients connected to the electrodes by isolating DC voltage. This inherent safety feature in the circuit eliminates the need for additional safety circuitry.

[0041] In one or more embodiments, the selection block may include an H-bridge circuit.

[0042] The use of an H-bridge provides a particularly efficient way to continuously change the power level associated with the electrical signal (S).

[0043] In one or more embodiments, the selection block may include a charging capacitor having a first node coupled between a power supply terminal that can be coupled to a second power supply voltage source and a ground terminal that can be coupled to ground, wherein the charging capacitor is configured to selectively discharge through the H-bridge circuit based on the at least one square wave input signal, and wherein the selective discharge of the charging capacitor is configured to provide the combined signal at the output of the selection block.

[0044] Such implementations can provide a particularly advantageous and efficient way of providing the combined signal at the output of the selection block.

[0045] In one or more embodiments, the H-bridge circuit may include: a first inverter branch, the first inverter branch including a first power switching element and a second power switching element; a second inverter branch, the second inverter branch including a third power switching element and a fourth power switching element; the first power switching element and the third power switching element are respectively connected between the power supply terminal coupled to the second DC power supply voltage and the first output terminal and the second output terminal of the H-bridge circuit; the second power switching element and the fourth power switching element are connected between the first output terminal and the second output terminal of the H-bridge circuit and a ground terminal coupled to ground.

[0046] Such implementations can provide a particularly efficient H-bridge design capable of continuously managing high current loads (such as 120-200 amps).

[0047] In one or more embodiments, the power switching element may be a power MOSFET. MOSFETs, such as silicon carbide MOSFETs, can provide particularly advantageous components for handling the current and voltage required by the switching block.

[0048] In one or more embodiments, the gate terminal of each of the first power switching element, the second power switching element, the third power switching element, and the fourth power switching element may be controlled in response to the at least one square wave input signal to provide a continuous variation in the power level associated with the electrical signal (S).

[0049] Such implementations can provide a particularly advantageous way to control the switching of the H-bridge circuit.

[0050] In one or more embodiments, the filtering and electrical isolation block may include at least one of the following: a first series resonant filter configured to generate the sine wave signal by converting the square wave combination signal at the output of the selection block; a step-up transformer configured to provide the electrical isolation by amplifying the sine wave signal to generate another sine wave signal; and a second series resonant filter configured to provide filtering of the other sine wave to generate the electrical signal to be supplied to the electrode.

[0051] The first series resonant filter provides an efficient way to convert the combined signal into a sinusoidal signal. The step-up transformer, in addition to boosting the voltage to a predetermined level, also provides advantageous electrical isolation between the signal conversion and filtering. For example, the step-up transformer can be a 1:3 or 1:4 transformer. The second series resonant filter advantageously filters out low-frequency signals (which might otherwise pose a risk of harm to the patient, such as by stimulating the heart) and high-frequency signals.

[0052] In one or more embodiments, the first series resonant filter may include a bandpass filter configured to convert the combined signal into the sinusoidal signal at a predetermined frequency.

[0053] The bandpass filter may include one or more inductors and capacitors. The bandpass filter can be an efficient way to convert a square wave into a sine wave.

[0054] In one or more embodiments, the step-up transformer may include a step-up transformer having a high-frequency ferrite core.

[0055] In one or more embodiments, the second series resonant filter may include one or both of the following: an inductor choke, wherein the inductor choke is configured to provide filtering for frequencies above the predetermined frequency; and at least one filter capacitor, wherein the filter capacitor is configured to provide filtering for frequencies below the predetermined frequency.

[0056] One or both of an inductor choke and a capacitor can provide a particularly effective way to provide filtering at a predetermined frequency. This avoids providing a virtual ground within the second series resonant filter. This, in turn, helps ensure that other systems coupled to the electrodes (such as calibration and ECG systems) are not affected by the power module.

[0057] In one or more embodiments, the filtering and isolation block may further include one or both of the following: a current measurement circuit configured to measure the current of the electrical signal (S); and a voltage measurement circuit configured to measure the voltage of the electrical signal (S).

[0058] Providing one or both of direct current and voltage measurements of the electrical signal (S) within the filtering and isolation block can provide a true measure of the current, voltage, and / or power applied to the electrodes applied to the patient. This allows for improved determination of the signal applied to the patient, and thereby improved control of the signal applied to the patient.

[0059] In one or more embodiments, the power generator may further include a drive circuit configured to receive a first drive signal (PS1) and a second drive signal (PS2), wherein the drive circuit is configured to amplify the first drive signal and the second drive signal to provide a first square wave input signal and a second square wave input signal to the selection block.

[0060] While the switching block may be controlled by at least one square wave, providing two square waves makes it easier to achieve the required high switching speed, while avoiding the need for particularly large or expensive components that can switch at the necessary speed and voltage.

[0061] In one or more embodiments, the first drive signal and the second drive signal may be received from a single control unit.

[0062] A single control unit can be configured to efficiently generate and provide two drive signals and ensure that, in some implementations, these two drive signals do not simultaneously provide logic high signals. This can be achieved by providing two drive signals that are 180 degrees out of phase with each other, and can be further achieved by providing a duty cycle of less than 50% for each signal to ensure that there is no overlap between the logic high cycles of the signals.

[0063] In one or more embodiments, the drive circuit can be configured as an emitter follower.

[0064] An emitter follower configuration can provide an advantageous amplifier arrangement that optimally utilizes the components of the driver circuit.

[0065] In one or more embodiments, the drive circuit may include a first amplifier circuit and a second amplifier circuit, wherein each of the first amplifier circuit and the second amplifier circuit is arranged in an identical emitter follower configuration, and each amplifier circuit is connected between a power supply terminal coupled to a first DC power supply voltage and a ground potential (GND) terminal for connection to ground.

[0066] Providing an amplifier circuit for each drive signal can be a particularly effective way to amplify both the first and second drive signals.

[0067] In one or more embodiments, the power generator may include a transformer circuit disposed between the drive circuit block and the selection block, wherein the transformer circuit is configured to provide electrical isolation between the drive circuit and the selection block.

[0068] The provision of transformer circuitry provides further electrical isolation between the patient and the power source and drive signals, thereby providing further inherent protection in the circuit, while also providing an efficient way to drive H-bridge circuitry.

[0069] In one or more embodiments, the transformer circuit may include a primary winding having a first terminal coupled to a first output terminal of the drive circuit block and a second terminal coupled to a second output terminal of the drive circuit block, and the transformer may further include a primary winding, a secondary winding, a tertiary winding and a quaternary winding.

[0070] A transformer circuit, coupled to a first and second output terminal of the drive circuit (which correspond to the output terminal of the amplifier circuit), provides a particularly efficient way to provide two input signals to the H-bridge. It should be understood that in this arrangement, where the first output terminal of the drive circuit is coupled to the first terminal of the transformer and the second output terminal of the drive circuit is coupled to the opposite second terminal of the drive circuit, the output signal of the transformer can be relatively considered as logic high (logic 1), logic zero (logic 0), and logic low (logic -1). It should also be understood that, as used herein, “logic high” (logic 1) can refer to a positive voltage signal, but does not necessarily have to. Similarly, “logic zero” (logic 0) can, but does not necessarily, refer to a zero voltage signal. Finally, “logic low” (logic -1) can, but does not necessarily refer to a negative voltage signal. These designations are merely intended to provide an easy relative reference to which these voltages can be relative to each other.

[0071] In one or more embodiments, the first drive signal and the second drive signal may be provided to the drive circuit such that the first square wave input signal and the second square wave input signal are not provided to the transformer circuit simultaneously.

[0072] Receiving drive signals configured not to be simultaneously supplied to the transformer can avoid providing conflicting voltages in the circuit that could damage components.

[0073] In one or more embodiments, each of the first secondary winding, the second secondary winding, the third secondary winding, and the fourth secondary winding is coupled to a corresponding one of the first power switching element, the second power switching element, the third power switching element, and the fourth power switching element of the H-bridge circuit, such that the first square wave input signal and the second square wave input signal provide control over the first power switching element, the second power switching element, the third power switching element, and the fourth power switching element.

[0074] Using two input signals provided by a transformer to drive the power switching elements of the H-bridge provides a particularly coordinated system that can handle the voltage, current, and power required in the switching block, thereby providing a switching signal with an amplitude high enough to switch the power switching elements rated for such conditions, while also electrically isolating the switching block components from the drive signals to protect these components.

[0075] According to a second aspect of this disclosure, a method is provided for supplying electrical energy to at least one electrode of an electronic device for delivering coherent sinusoidal burst irreversible electroporation energy, comprising: receiving at least one square wave input signal at a selection block; continuously changing the power level associated with the electrical signal (S) based on the at least one square wave input signal to provide a combined signal comprising a square wave waveform; receiving the combined signal from the selection block at an input of a filtering and electrical isolation block; converting the combined signal into a sinusoidal signal; and filtering the sinusoidal signal to generate the electrical signal (S), wherein the conversion and the filtering are electrically isolated from each other.

[0076] According to a third aspect of this disclosure, a method is provided for supplying electrical energy to at least one electrode of an electronic device for delivering coherent sinusoidal burst irreversible electroporation energy, wherein the at least one electrode is positioned within a patient, the method comprising: receiving at least one square wave input signal at a selection block; continuously changing an electrical energy level associated with the electrical signal (S) based on the at least one square wave input signal to provide a combined signal comprising a square wave waveform; receiving the combined signal from the selection block at an input of a filtering and electrically isolated block; converting the combined signal into a sinusoidal signal; and filtering the sinusoidal signal to generate the electrical signal (S), wherein the conversion and the filtering are electrically isolated from each other.

[0077] According to a fourth aspect of this disclosure, an electronic device is provided for delivering coherent sinusoidal burst irreversible electroporation energy, comprising: a power unit for supplying electrical energy to at least one electrode, the power unit including at least one power module configured to generate an electrical signal (S) to energize one or more corresponding electrodes, the or each power module including: a selection block configured to receive at least one square wave input signal, wherein the selection block is configured to continuously change the power level associated with the electrical signal (S) based on the at least one square wave input signal to provide a combined signal at the output of the selection block, wherein the combined signal includes a square wave waveform; and a filtering and electrical isolation block configured to convert the combined signal into a sinusoidal signal and filter the sinusoidal signal to generate the electrical signal (S), wherein the conversion and the filtering are electrically isolated from each other. Attached Figure Description

[0078] Other features and advantages of the invention will become apparent from the following description, with reference to the accompanying drawings, of exemplary embodiments of the invention given by way of non-limiting example, in which:

[0079] - Figure 1 An electronic device according to the invention for delivering coherent sinusoidal burst irreversible electroporation energy or IRE to biological tissue is schematically shown, wherein the electronic device includes a plurality of electrodes that can be positioned on or near the biological tissue to be treated, and a power generator for supplying electrical energy to each of these electrodes.

[0080] - Figure 2 Shown in block diagram Figure 1 A power generator for electronic devices, comprising a single control unit and a power unit;

[0081] - Figure 3 The graph shows how it changes over time. Figure 1 An example of an electrical signal generated by a power generator that alternates between a first electrical signal and a second electrical signal over time;

[0082] - Figure 4 Shown at a higher resolution Figure 3 The diagram represents the portion of the first electrical signal;

[0083] - Figure 5 The Fourier analysis of the first electrical signal, which consists of eleven basic 50kHz sine waves, is presented.

[0084] - Figure 6 exhibit Figure 2 An example of the circuit structure of one of the six power modules included in the power unit of a power generator;

[0085] - Figure 7 , Figure 8 and Figure 9 Shown in magnified view Figure 6 The circuit part of the power module circuit structure;

[0086] - Figure 10A and Figure 10B An electronic device according to the invention for delivering coherent sinusoidal burst irreversible electroporation energy or IRE to biological tissue is schematically shown, wherein the electronic device includes a first electrode and a second electrode that can be positioned on or near the biological tissue to be treated, and a power generator configured to supply “in-phase” or “out-of-phase” sinusoidal electrical signals to the two electrodes respectively.

[0087] - Figure 11 schematically shown by Figure 1The device has multiple electrodes powered by a power generator, wherein the electrodes are operatively associated with a catheter and can be positioned on or near the myocardial tissue to be treated, and are configured to deliver a combination of bipolar and unipolar voltages or alternating unipolar and bipolar voltage fields.

[0088] - Figure 12 exhibit Figure 2 An alternative example of the circuit structure of one of the six power modules included in the power unit of the power generator;

[0089] Identical or similar elements are indicated by the same reference numerals in the diagram. Detailed Implementation

[0090] The invention will be more readily understood by referring to the following detailed description, examples, drawings, and contextual description. Therefore, before disclosing and describing the apparatus, system, and / or method of the invention, it should be understood that, unless otherwise stated, the invention is not limited to specific apparatus, system, and / or method, as they can naturally vary. It should also be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.

[0091] The following description of the invention is provided as enabling doctrine with respect to its best currently known embodiments. Therefore, those skilled in the art will recognize and understand that many changes can be made to various aspects of the invention described herein while still obtaining the beneficial results of the invention. It will also be apparent that some of the desired benefits of the invention can be obtained by selecting some features of the invention without utilizing others. Therefore, those skilled in the art will recognize that many modifications and adaptations to the invention are possible and, in some cases, even desirable, and are part of the invention.

[0092] According to the general implementation plan, refer to Figure 1 The electronic device according to the invention for delivering coherent sinusoidal burst irreversible electroporation energy or IRE to the biological tissue 1 to be treated is generally indicated by reference numeral 100.

[0093] The electronic device 100 includes a plurality of electrodes 3 that can be positioned on or near the biological tissue 1 to be treated, and a power generator 2 for supplying electrical energy to each of the plurality of electrodes 3. Specifically, the plurality of electrodes (in...) Figure 1 The example shows six electrodes 3) in which electrode 3 is operatively associated with catheter 4.

[0094] In a preferred embodiment, the biological tissue to be treated 1 is heart tissue.

[0095] The power generator 2 is specifically connected to the electrodes 3 via six wires 7 and is configured to generate an electrical signal S to energize each of the electrodes 3, that is, to apply a voltage electric field to the biological tissue 1 through the electrodes 3.

[0096] Furthermore, the electronic device 100 includes another electrode 5, which serves as a return electrode for the voltage and electric field applied to the biological tissue 1. Specifically, this return electrode 5 or backplate is electrically connected to the power generator 2 via a corresponding return wire 6.

[0097] In an alternative embodiment (not shown), the electronic device 100 may include a single electrode 3 that can be positioned on or near the biological tissue 1 to be treated. A power generator 2 is electrically connected to this single electrode 3 and is configured to generate an electrical signal S to energize the electrode 3, i.e., to apply a voltage electric field to the biological tissue 1 through the single electrode 3.

[0098] For more details, see the reference. Figures 3 to 4 The electrical signal S is formed by alternating between a first electrical signal S1 and a second electrical signal S2 over time. The first electrical signal S1 is supplied to the electrode 3 during a first time interval T1, and the second electrical signal S2 is supplied to the electrode 3 during a second time interval T2 following the first time interval T1.

[0099] The first electrical signal S1 is a continuous bipolar signal comprising two or more fundamental sine waves SB within the first time interval T1. Each fundamental sine wave consists of a positive half-wave and a negative half-wave. The second electrical signal S2 has an amplitude equal to zero within the second time interval T2.

[0100] For example, Figure 3 The described electrical signal S includes three electrical signals S1, wherein two of the first electrical signals S1 are separated from each other by a second electrical signal S2 that is zero during a second time interval T2.

[0101] In an alternative implementation, the first electrical signal S1 includes two or more fundamental sine waves SB that are repeated within the first time interval T1.

[0102] Regarding this invention, the applicant proposes a power unit configured to generate an electrical signal S for ablating tissue 1, said electrical signal S consisting of a plurality of sinusoidal bursts (i.e., a plurality of first electrical signals S1), said plurality of sinusoidal bursts being spaced apart by cooling cycles in which no electrical energy is transmitted to electrode 3 (i.e., second electrical signals S2). The sinusoidal bursts are generated in a manner that avoids cardiac stimulation even when applied for a relatively long period of time. This is achieved by selecting waveforms such that the net voltage of harmonics generated in the region between 1 Hz and 200 Hz is negligible. In fact, to avoid cardiac stimulation, the frequency intervals of 1 Hz and 200 Hz must be avoided.

[0103] In more detail, Figure 3 The diagram of the electrical signal S shown includes three sine wave bursts, each separated by a 1.5-millisecond cooling cycle.

[0104] exist Figure 5 The diagram depicts a Fourier analysis of the first electrical signal S1, comprising, for example, eleven fundamental sine waves SB at 50 kHz. Specifically, this Fourier analysis shows that the voltage amplitude of the 50 kHz signal component (i.e., the desired component) is 67 dB higher than that of the 150 Hz signal component (which is the harmful component). Specifically, the 1.5 kV peak voltage of the 50 kHz signal component corresponds to approximately 0.0005 V of the peak voltage of the 150 Hz signal component, i.e., a near-zero peak voltage that would not cause cardiac stimulation.

[0105] In contrast, traditional IRE square wave signals have a 150Hz signal component with a voltage of about 6V, which poses a significant risk of cardiac stimulation.

[0106] According to one embodiment, the first electrical signal S1 has a frequency in the range of 25-49 kHz. According to another embodiment, the first electrical signal S1 has a frequency in the range of 25-75 kHz.

[0107] According to one or more embodiments, the first electrical signal S1 has a frequency in the range of 35-65 kHz. According to one or more embodiments, the first electrical signal S1 has a frequency in the range of 40-60 kHz. According to one or more embodiments, the first electrical signal S1 has a frequency in the range of 45-55 kHz. According to one or more preferred embodiments, the first electrical signal S1 has a frequency of 50 kHz.

[0108] According to an alternative implementation, the first electrical signal S1 includes two to fifteen basic sine waves SB within the first time interval T1.

[0109] In fact, according to the tissue ablation requirements, when the voltage applied to tissue 1 via electrical signal S is selected to be higher, generator 2 provides a first electrical signal S1 comprising fewer cycles of the fundamental sine wave SB repeated within the first time interval T1, i.e., fewer cycles of the first electrical signal S1 and the second electrical signal S2 are required. Conversely, when the voltage applied to tissue 1 via electrical signal S is selected to be lower, generator 2 provides a first electrical signal S1 comprising more cycles of the fundamental sine wave SB repeated within the first time interval, i.e., fewer cycles of the first electrical signal S1 and the second electrical signal S2 are required. Therefore, the voltage applied to tissue 1 via electrical signal S can be obtained as a trade-off between the number of cycles and the number of cycles of the fundamental sine wave SB repeated within the first time interval T1.

[0110] According to the alternative implementation, the second time interval T2 (i.e., the cooling cycle) of the second signal S2 has a duration of at least 1 millisecond to 1 second.

[0111] Specifically, the duration of the second time interval T2 can be changed according to the heat dissipation requirements.

[0112] According to the alternative implementation, the peak-to-peak average amplitude of each basic sine wave SB is in the range of 2,000V to 20,000V. The preferred amount depends on the organization. Specifically, when the power generator 2 is powered on, the initial setting can be -2.5kV and +2.5kV, and then changed to suit various organizational requirements.

[0113] Typically, according to some implementation schemes, the characteristics of the electrical signal S can be changed as long as the amplitude of the signal component below a predetermined threshold is negligible. Typically, according to some implementation schemes, the characteristics of the electrical signal S can be changed as long as the amplitude of the signal component below 200Hz is negligible.

[0114] According to the reference Figures 1 to 2 In the described alternative embodiment, the power generator 2 includes a single control unit 200 and a power unit 201 for generating an electrical signal S. Specifically, the power unit 201 is electrically connected to all of the plurality of electrodes 3.

[0115] According to an alternative implementation, the power unit 201 is driven by the single control unit 200 to change the number of fundamental sine waves SB that repeat within the first time interval T1, thereby modifying the power level associated with the signal S to be supplied to the electrode 3.

[0116] According to an alternative implementation, the power unit 201 is driven by the single control unit 200 to change the duration of the second time interval T2, thereby modifying the power level associated with the signal S to be supplied to the electrode.

[0117] According to an alternative implementation, the power unit 201 includes a power module 202, which is driven by a single control unit 200 to generate the first electrical signal S1 during a first time interval T1 and the second electrical signal S2 during a second time interval T2.

[0118] Power module 202 may include:

[0119] - Selection block 204, which is selectively controlled by a square wave signal, wherein the selection block is configured to change the power level associated with the electrical signal S; and

[0120] - Filtering and electrical isolation blocks 205, 206, 205'.

[0121] Specifically, the power module 202 may include:

[0122] - Drive circuit block 203, which is controlled by single control unit 200 to generate the first electrical signal S1 or the second electrical signal S2 respectively from drive signals PS1, PS2 or signal zero provided by single control unit 200;

[0123] - Selection block 204, which is selectively controlled by the drive circuit block 203 to continuously change the power level associated with the electrical signal S;

[0124] - Filtering and electrical isolation blocks 205, 206, 205'.

[0125] According to alternative embodiments, the single control unit 200 includes one or more of a microprocessor 207 and a programmable logic controller block 209 configured to control a variable high-voltage power supply block 208. The variable high-voltage power supply block 208 is configured to provide supply voltage signals Vcc and Vcc1 to the power module 202 for generating an electrical signal S. More specifically, the supply voltage signals include a first DC power supply voltage Vcc and a second DC power supply voltage Vcc1. The first power supply voltage Vcc and the second power supply voltage Vcc1 are connected in parallel with corresponding protection capacitors C10 and C2. In one or more embodiments, such as those excluding the drive circuit block 203, voltage Vcc may not be required. The supply voltage Vcc can provide a voltage of 10-25 volts, 15-20 volts, or preferably 18 volts. The supply voltage Vcc1 can provide a voltage of 100-1000 volts, 150-500 volts, 175-300 volts, or, for example, 250 volts. The supply voltage Vcc1 can be a variable power supply voltage, which is configured to vary between one or more of the ranges listed above or another voltage range. Figure 12 An exemplary implementation is shown, which does not utilize a driver block, but does include... Figure 6 The diagram shows similar switching blocks, as well as filtering and isolation blocks.

[0126] Programmable Logic Controller (PLC) block 209 is configured to generate the drive signals PS1, PS2 to control the drive circuit block 203 of power module 202. The PLC is particularly advantageous for generating signals PS1 and PS2 because these signals need to be provided at high frequencies, and the PLC is particularly well-suited for this purpose compared to alternative implementations for generating these signals.

[0127] In one or more alternative embodiments, the programmable logic controller block 209 may not be necessary, and instead, PS1 and PS2 may be generated by a microprocessor device. In yet another alternative embodiment, hard logic application-specific integrated circuits (ASICs) may be used to generate signals PS1 and PS2.

[0128] In some implementations, a single drive signal PS can be used to provide one square wave drive signal instead of two square wave signals. In such implementations, the first drive signal can be considered the same as the second drive signal. However, the practicality of generating such a single drive signal using one of the methods described above or alternative methods can be challenging. Therefore, the generation of the first drive signal PS1 and the second drive signal PS2 can be particularly advantageous. In some implementations, the second drive signal PS2 can be generated based on the first drive signal PS1, while in other implementations, the first drive signal PS1 and the second drive signal PS2 can be generated independently.

[0129] In one or more embodiments, the one or two drive signals can be bipolar square wave signals or unipolar square wave signals. That is, the voltage levels of the one or two drive signals can be set to relative zero volts and relative positive voltages, or the voltage levels can be set to relative positive voltages and relative negative voltages. In other examples, the two voltages can be relatively positive or relatively negative relative to a reference voltage. It should be understood that each of these voltages can be equivalent and only relative to a voltage defined as zero volts for circuit purposes.

[0130] Accordingly, in one or more embodiments, the square wave input signal can be a bipolar square wave signal or a unipolar square wave signal. That is, the voltage level of the square wave signal can be set to a relative zero volt and a relative positive voltage, or the voltage level can be set to a relative positive voltage and a relative negative voltage. In yet another example, the two voltages can be relatively positive or relatively negative relative to a reference voltage. It should be understood that each of these voltages can be equivalent and only relative to a voltage defined as zero volt for circuit purposes.

[0131] The single control unit 200 may also include one or more of the following:

[0132] - Video interface and button blocks 210, 210', which are controlled by microprocessor 207 to set parameters of electronic device 100 and display the selected parameters;

[0133] - Watchdog block 211, which is used to control the normal operation of microprocessor 207;

[0134] - Audio interface block 212, which is used to provide audio information indicating the correctness of the electroporation process and / or the errors that have occurred.

[0135] The control unit 200 may also include visual feedback elements, such as light bars capable of emitting a variety of different colors, which provide visible cues and / or information related to the operating status or processing of the control unit, and / or any errors encountered by the control unit 200.

[0136] According to an alternative embodiment, power unit 201 includes one or more identical power modules 202. Figure 2 In the example, power unit 201 includes six power modules 202; however, other numbers of power modules 202 may exist, such as two, four, or eight power modules 202. Each power module 202 is configured to generate an electrical signal S and supply it to an electrode 3.

[0137] According to one embodiment, at least one of the electrodes 3 of the plurality of electrodes is a unipolar electrode, and the unipolar electrode is electrically connected to only one power module 202 of the power unit 201.

[0138] In another embodiment, at least two of the electrodes 3 of the plurality of electrodes are electrically connected to form a bipolar electrode, and the bipolar electrode is electrically connected to a corresponding power module 202, which may be selected from the power modules of the power unit 201.

[0139] According to one embodiment, in order to provide a bipolar voltage or a combination of bipolar and unipolar voltages, the electrical signals at the output terminals of two or more power modules 202 of the power unit 201 must be selected. For example, the power unit 201 may include two, four, six, or eight identical power modules 202. Specifically, refer to... Figure 2 From top to bottom, they are the first power module 2021, the second power module 2022, the third power module 2023, the fourth power module 2024, the fifth power module 2025, and the sixth power module 2026.

[0140] A single pair can be formed by power modules 2021 and 2022, or power modules 2022 and 2023, or power modules 2023 and 2024, or power modules 2024 and 2025, or power modules 2025 and 2026.

[0141] All power modules 2021-2026 return lines are connected together and correspond to return line 6.

[0142] For example, to provide a bipolar voltage or a combination of bipolar and unipolar voltages, the electrical signals S generated by the first power module 2021, the third power module 2023, and the fifth power module 2025 are all at the same first phase value. The electrical signals S generated by the second power module 2022, the fourth power module 2024, and the sixth power module 2026 are all at a second phase value different from the first phase value.

[0143] According to an exemplary implementation, when the difference between the first phase value and the second phase value is 60 degrees, the bipolar voltage generated by the two adjacent power modules is the same as the unipolar voltage.

[0144] According to alternative implementations, the power generator 2 is powered by a battery or connected to a standard wall outlet capable of generating 110 volts or 240 volts of AC power.

[0145] According to an alternative embodiment, each power module 202 may include a drive circuit block, wherein each drive circuit block includes amplifier circuitry. The amplifier circuitry 203 may be arranged in an emitter follower configuration.

[0146] In the emitter follower configuration, to generate the first electrical signal S1 of the electrical signal S, the amplifier circuit 203 is configured to amplify the drive signals generated by the single-control unit 200. These drive signals include a first pulse signal PS1 and a second pulse signal PS2 supplied by the single-control unit 200. Specifically, the first pulse signal PS1 comprises a first square wave, and the second pulse signal PS2 comprises a second square wave, wherein the second square wave is 180 degrees out of phase with the first square wave. Furthermore, the duty cycle of the first pulse signal PS1 and the second pulse signal PS2 can be selected, i.e., a switching cycle, so that the primary winding L1 is not simultaneously driven by signals PS1 and PS2. In this way, conflicts between the signals and potential damage can be avoided. More specifically, the first pulse signal PS1 can be turned on, i.e., providing "logic high," for a first cycle, for example, 10 μs; then both pulse signals PS1 and PS2 are turned off, i.e., providing "logic zero," for example, for a clock cycle of approximately 62.5 ns; then the second pulse signal PS2 is turned on, i.e., providing "logic low," for a second cycle, for example, 10 μs; then both pulse signals PS1 and PS2 are turned off again, for example, for a clock cycle of approximately 62.5 ns, and this duty cycle repeats. The amplifier circuit 203 arranged in this way provides level shifting of the input signals PS1 and PS2 so that they are suitable for driving the H-bridge circuit 204.

[0147] In order to generate the second electrical signal S2 of the electrical signal S, the single control unit 200 is configured to supply the corresponding drive signal zero to the amplifier circuit 203.

[0148] In other embodiments, power module 202 may be configured to provide drive signals to H-bridge circuit 204 without a drive circuit block. Instead, for example, power module 202 may include circuitry and logic suitable for driving the H-bridge. Alternatively, a drive circuit block may be provided, comprising an operational amplifier of appropriate size capable of providing drive signals, thus eliminating the need for emitter follower arrangements and transformer circuitry. The advantage of this implementation is that the H-bridge handles lower voltages, and therefore the electronics therein only need to have lower voltage ratings. However, a larger transformer 206 will be required later in the circuit to boost such low voltages to the high voltages required for irreversible electroporation. This larger transformer 206 later in the circuit will, in turn, require a larger current in its primary winding (leading to complexity), rather than utilizing the current ratings of the electronics in the H-bridge.

[0149] As described in more detail later, a drive circuit block comprising an amplifier circuit arranged in an emitter follower configuration may be configured to drive an H-bridge circuit of a selection block via a first transformer circuit 230, the first transformer circuit comprising a first primary winding L1 and four distinct secondary windings L2-L5. In some embodiments, the primary and secondary windings may be arranged around a single common core such that they are electrically isolated but magnetically coupled. In other embodiments, different arrangements may be implemented to provide the first transformer circuit 230. The secondary coils may comprise a first pair of secondary windings such as secondary windings L2 and L5, and a second pair of secondary windings such as secondary windings L3 and L4. The first pair of secondary windings is arranged such that they receive signals PS1 and PS2 from the primary winding in phase 180 degrees with the second pair of secondary windings. This is in Figure 6 The term is represented by the points on the secondary winding and whether the pointed or unpointed side of the winding is coupled to the gates of their respective FETs M1-M4.

[0150] The use of the first transformer circuit 230 and the magnetic coupling it provides between the amplifier circuit 203 and the H-bridge can be particularly advantageous because it provides electrical isolation between these two parts of the circuit. This means that if any fault occurs on the amplifier circuit side of the first transformer circuit 230, the field-effect transistors (FETs) of the H-bridge 204 will simply turn off because no signal will be supplied to their gate terminals, and therefore the H-bridge will have a zero output signal. This provides protection not only for the electronics of the H-bridge 204 but also for the patient, as the electronics and the patient are electrically isolated from the single-control unit 200.

[0151] According to an alternative implementation, each power module 202 selection block 204 includes an H-bridge circuit 204.

[0152] In order to generate the first electrical signal S1 of the electrical signal S, the H-bridge circuit 204 is configured to combine the first pulse signal PS1 and the second pulse signal PS2 (in some embodiments, the first pulse signal and the second pulse signal are amplified by the amplifier circuit 203) to generate a combined signal CS with a square waveform.

[0153] According to one or more embodiments, each power module 202 may include filtering and electrical isolation blocks 205, 206, 205':

[0154] - A first series resonant filter 205 is configured to generate a sine wave signal SW by converting the square wave combination signal CS generated at the output of the H-bridge circuit 204.

[0155] - Transformer 206, which is configured to amplify the sinusoidal signal SW to generate another sinusoidal signal SW1;

[0156] - A second series resonant filter 205' is configured to generate a first electrical signal S1 to be supplied to electrode 3 by filtering another sinusoidal signal SW1.

[0157] refer to Figures 6 to 7 The preferred embodiment of the amplifier circuit 203 with an emitter follower configuration is described in detail.

[0158] Amplifier circuit 203 includes a first amplifier circuit 203' and a second amplifier circuit 203" that are identically configured as emitter followers. Each amplifier circuit 203', 203" is connected between a first DC power supply voltage Vcc and a ground potential or a ground GND terminal that can be coupled to a ground potential. The ground potential can be a reference voltage, such as a relative 0-volt reference voltage. Any reference node or ground terminal mentioned herein may include a ground node set to a relative 0-volt, and any other ground terminal may be set to the same relative voltage, such as 0 volt, or set to a different relative reference voltage suitable for this part of the circuit. It should also be understood that, generally, a reference node, such as a ground node, is considered to be coupled to ground only when coupled to a power source. Therefore, those skilled in the art will understand that mentioning a terminal that can be coupled to ground is to explicitly mention that the circuit does not need to be coupled to a power source to be a circuit according to this disclosure but is configured to be so coupled in use.

[0159] The first amplifier circuit 203' includes a first input circuit M7, R1, Q1, Q3 configured to receive a first pulse signal PS1 as input. Specifically, the first input circuit includes a first MOSFET transistor M7, which is configured to receive the first pulse signal PS1 at its gate terminal and has a corresponding source terminal connected to ground GND. The first input circuit also includes a first resistor R1 connected between the first power supply voltage Vcc and the drain terminal of the first MOSFET transistor M7. In an emitter follower configuration, the drain terminal of the first MOSFET transistor M7 is electrically connected to the corresponding base terminal of a first BJT transistor (specifically, two BJT transistors Q1 and Q3), which is connected (through its respective collector terminal) between the first power supply voltage Vcc and ground GND. The emitter terminals of the first BJT transistors Q1 and Q3 are connected to the corresponding first output terminal OU1 of the first amplifier circuit 203'.

[0160] The second amplifier circuit 203” includes a second input circuit M8, R4, Q2, Q4 configured to receive a second pulse signal PS2 as input. Specifically, the second input circuit includes a second MOSFET transistor M8, which is configured to receive the second pulse signal PS2 at its gate terminal and has a corresponding source terminal connected to ground GND. The second input circuit also includes a second resistor R4 connected between the first power supply voltage Vcc and the drain terminal of the second MOSFET transistor M8. In an emitter follower configuration, the drain terminal of the second MOSFET transistor M8 is electrically connected to the corresponding base terminal of a second BJT transistor (specifically, two BJT transistors Q2 and Q4), which is connected (through its respective collector terminal) between the first power supply voltage Vcc and ground GND. The emitter terminals of the second BJT transistors Q2 and Q4 are connected to the corresponding second output terminal OU2 of the second amplifier circuit 203”.

[0161] The first pulse signal PS1 and the second pulse signal PS2 are provided to amplifier circuits 203' and 203'' so that their respective logic high signals do not overlap. This method of signaling is used to avoid damaging components of amplifier circuits 203' and 203''. By appropriately selecting the frequency and duty cycle of signals PS1 and PS2, they can be configured to not overlap.

[0162] Power module 202 includes a first transformer circuit 230 inserted between amplifier circuit drive or actuation circuit block 203 and H-bridge circuit 204. More specifically, transformer circuit 230 includes a power transformer or isolator having a primary winding L1 and four secondary windings (specifically, a primary winding L2, a secondary winding L3, a tertiary winding L4, and a fourth secondary winding L5). The primary winding to secondary windings can be provided in a 1:1 ratio of primary winding to each individual secondary winding.

[0163] The terminals of the primary winding L1 of the first transformer circuit 230 are respectively connected to the output terminals OU1 and OU2 of the first amplifier circuit 203' and the second amplifier circuit 203". The H-bridge circuit 204 includes a power inverter block 204, which is configured to generate a combined signal CS with a square waveform at its output terminal by combining the first pulse signal PS1 and the second pulse signal PS2 amplified by the amplifier circuit 203, starting from the second DC power supply voltage Vcc1.

[0164] For more details, see the reference. Figure 6 and Figure 8 The following describes an example of the H-bridge power inverter block 204 included in the power module 202 of the present invention.

[0165] This power inverter block includes the drive section 204' of the H-bridge inverter and the power section 204 of the H-bridge inverter.

[0166] Specifically, the power section 204” of the H-bridge inverter 204 includes:

[0167] - The first inverter branch B1 includes a first power MOSFET (metal-oxide-semiconductor field-effect transistor) M1 and a second power MOSFET M2;

[0168] - The second inverter branch B2 includes the third power MOSFET M3 and the fourth power MOSFET M4.

[0169] MOSFETs may include silicon carbide field-effect transistors or different types of field-effect transistors. Silicon carbide field-effect transistors are particularly suitable for the H-bridge circuit 204, especially when each silicon carbide field-effect transistor is rated for continuous operation at 120 amperes. In some embodiments, providing two parallel transistors on each inverter branch allows the parallel transistor arrangement to be continuously maintained at more than 200 amperes.

[0170] The first power MOSFET M1 and the third power MOSFET M3 are respectively connected between the power supply terminal at the second DC power supply voltage Vcc1 and the first output terminal O1 and the second output terminal O2 of the H-bridge circuit 204 through the resistor R5 of the second DC power supply voltage.

[0171] The second power MOSFET M2 and the fourth power MOSFET M4 are connected between the first output terminal O1 and the second output terminal O2 of the H-bridge circuit 204 and the ground potential GND.

[0172] The power supply Vcc1 can be implemented as a supply voltage Vcc1 followed by a downstream resistor, such as resistor R5. Resistor R5 can be configured to limit the current delivered to capacitor C2 to prevent the circuit from drawing excessive power from the charging power supply Vcc1. In one or more alternative embodiments, Vcc1 and resistor R5 can be replaced by a current source provided by a dedicated power source for the H-bridge; said current source can alternatively originate from the variable high-voltage power supply block 208. Figure 12 An example is shown where the charging capacitor C2 is provided as a capacitor bank, and the power supply Vcc1 is a current source, requiring no additional resistor.

[0173] The H-bridge circuit includes a power inverter 204, which includes a drive section 204'. The drive section 204' of the H-bridge inverter 204 is described in detail below.

[0174] Specifically, the gate terminal of the first power MOSFET M1 is connected to one terminal of the first primary winding L2 via a third resistor R8. The first output terminal O1 of the H-bridge circuit 204 is connected to the gate terminal of the first power MOSFET M1 via a first diode D2 connected in series with a fourth resistor R11. The other terminal of the first primary winding L2 is directly connected to the first output terminal O1 of the H-bridge circuit 204.

[0175] Furthermore, the gate terminal of the third power MOSFET M3 is connected to one terminal of the third stage winding L4 via the fifth resistor R3. The gate terminal of the third power MOSFET M3 is connected to ground GND via the sixth resistor R13, which is connected in series with the second diode D4. The other terminal of the third stage winding L4 is directly connected to the second output terminal O2 of the H-bridge circuit 204.

[0176] Additionally, the gate terminal of the second power MOSFET M2 is connected to one terminal of the secondary winding L3 via the seventh resistor R9. The gate terminal of the second power MOSFET M2 is connected to ground (GND) via the eighth resistor R10, which is connected in series with the third diode D1. The other terminal of the secondary winding L3 is directly connected to ground (GND).

[0177] Additionally, the gate terminal of the fourth power MOSFET M4 is connected to one terminal of the fourth secondary winding L5 via the ninth resistor R7. The gate terminal of the fourth power MOSFET M4 is connected to ground (GND) via the tenth resistor R12, which is connected in series with the fourth triode diode D3. The other terminal of the fourth secondary winding L5 is directly connected to ground (GND).

[0178] It should be noted that the H-bridge circuit 204 includes a power inverter block 204, which is configured to generate a combined signal CS with a square waveform between the first output terminal O1 and the second output terminal O2, which are interconnected by the output resistor R6.

[0179] Specifically, capacitor C2 is charged by a power supply Vcc1, which may or may not be a current source. This charging can be provided continuously, but this is not necessarily the case, and it is not the case in the exemplary embodiment shown. In the exemplary embodiment shown, when a logic high signal is received from driver circuit 203', MOSFETs M1 and M4 are turned on and thus capacitor C2 is connected across output resistor R6 in a first direction. This releases some current from capacitor C2 and generates a voltage across output resistor R6, which is equal in magnitude to the voltage stored in capacitor C2, i.e., Vcc1, and is output by H-bridge circuit 204 in the form of the first half (e.g., the upper half or positive half) of a square wave of combined signal CS. Simultaneously, when MOSFETs M2 and M3 receive a logic high signal from driver circuit 203', they are turned on (while MOSFETs M1 and M4 are turned off due to receiving a logic low signal from driver circuit 203'), thereby connecting capacitor C2 across output resistor in a second direction opposite to the first direction. This again releases some current from capacitor C2 and generates a voltage across output resistor R6, which is equal in magnitude to the remaining, slightly reduced voltage stored in capacitor C2, i.e., Vcc1'. This slightly reduced voltage is output by H-bridge circuit 204 in the form of the second half (e.g., the upper half or positive half) of the square wave of the combined signal CS. MOSFETs M1 and M4 then turn on again, while MOSFETs M2 and M3 turn off, and the selective switching of capacitor C2 across output resistor R6 in the first and second directions continues, wherein the resulting voltage generated across output resistor R6 decreases slightly on each successive half-square wave because capacitor C2 releases slightly more each time it discharges. Accordingly, H-bridge circuit 204 is controlled to output the combined signal CS with a square waveform having an amplitude approximately Vcc1×2.

[0180] Capacitor C2 can be appropriately sized so that each discharge triggered by a logic high signal PS1 or PS2 consumes only a small fraction of the total stored charge (i.e., stored voltage), allowing capacitor C2 to act as a reservoir for the stored charge. This helps minimize the small voltage amplitude drop across the output resistor R6 during continuous half-square wave output, ensuring that the combined signal CS output by the H-bridge circuit 204 continuously has a square waveform with an amplitude very close to Vcc1×2. For example, the capacitor can be a capacitor bank with a total capacitance of 2,000 microfarads to 10,000 microfarads. In one or more examples, the H-bridge circuit 204 needs to switch pulses at a voltage of +20V or -20V. However, the first MOSFET transistor M1, the second MOSFET transistor M2, the third MOSFET transistor M3, and the fourth MOSFET transistor M4 are only rated for gate voltages of -7V or higher. Therefore, for each MOSFET transistor M1-M4, the H-bridge circuit 204 includes corresponding diodes D1, D2, D3, and D4 connected to resistors R10, R11, R12, and R13 to limit the negative pulse to -7V.

[0181] It is understood that components M1-M4 do not need to be implemented as MOSFETs; however, components M1-M4 must be able to provide selective switching based on the received signal and must be able to manage the current and voltage required by the power generator to supply power to multiple electrodes of the electronic device used to deliver coherent sinusoidal burst irreversible electroporation energy. Alternatively, components M1-M4 can be implemented as any power switching element. In one or more embodiments, multiple components may be provided instead of a single component in components M1-M4. For example, two MOSFETs may be provided, each MOSFET having a gate terminal coupled to a common secondary winding for components M1-M4, such as in Figure 12 In this arrangement, the load can be isolated, and thus the burden can be isolated on a single power switching element.

[0182] After generating a combined signal CS with a square waveform at the H-bridge circuit 204, the power module 202 of the present invention includes a first series resonant filter 205 for converting the combined signal CS into a sine wave signal SW.

[0183] refer to Figure 6 A first series resonant filter 205 is connected between the output of the H-bridge circuit 204 and a transformer 206, which is configured to amplify the sinusoidal signal SW to generate an additional sinusoidal signal SW1. The transformer 206 includes a first winding L6 and a second winding L8. The additional sinusoidal signal SW1 is provided between a corresponding first terminal of the second winding L8 of the transformer 206 and a corresponding second terminal connected to ground GND.

[0184] According to an exemplary embodiment, transformer 206 is a 1:3 ratio step-up isolation transformer with a high-frequency ferrite core. In yet another embodiment, transformer 206 is a 1:4 ratio step-up isolation transformer with a high-frequency ferrite core. It should be understood that other step-up ratios may be used alternatively. In one or more embodiments, the high-frequency ferrite core may be configured to operate in a frequency range of 40-60 kHz. In other embodiments, the high-frequency ferrite core may be configured to operate in a frequency range of 35-65 kHz. In other embodiments, the high-frequency ferrite core may be configured to operate in a frequency range of 45-55 kHz. In other embodiments, the high-frequency ferrite core may be configured to operate at a frequency of 50 kHz.

[0185] More specifically, this first series resonant filter 205 may include an inductor L14 connected in series with a capacitor C1. The resulting sinusoidal signal is then amplified by a transformer L6 / L8. The values ​​of the inductor L14 and the capacitor C1 are determined by the specific application of the IRE.

[0186] Alternatively, the first series resonant filter 205 may have an alternative arrangement. In one or more alternative embodiments, the first series resonant filter 205 may include a group of four inductors arranged in parallel such that the input of each inductor is coupled to the output of the H-bridge circuit, and the outputs of each of the four inductors are coupled together to provide a common inductor output, such as in... Figure 12 In the example shown, the first series resonant filter 205 may further include a set of four capacitors arranged in parallel such that the common output of the four parallel inductors is coupled to the common input of the four parallel capacitors, and the four parallel capacitors are connected to the output of a common capacitor that is connected to the input of the transformer 206, such as in... Figure 12 In the example shown, it should be understood that different plurality of parallel inductors and parallel capacitors may be implemented in the first series resonant filter 205.

[0187] The first series resonant filter 205 is, for example, a bandpass filter configured to filter out all harmonic components of the combined square wave signal CS except for the fundamental harmonic selected for the sinusoidal signal SW. For example, for a fundamental harmonic of 40 kHz, typical values ​​for inductor L14 and capacitor C1 are, for example, L14 = 10 μH and C1 = 1 μF.

[0188] Since the output voltage of the first sinusoidal electrical signal S1 required for electroporation is high, the power module 202 of the present invention also advantageously includes a second series resonant filter 205'.

[0189] This second series resonant filter 205' needs to have significantly higher capabilities than series resonant filters known in the art, such as filters used for radio frequency ablation or RFA.

[0190] This second series resonant filter 205' is not required in RFA generators and square wave PFA generators known in the art.

[0191] According to one embodiment, this second series resonant filter 205' is connected between the transformer 206 and the load R2 of the power module 202. Specifically, the second series resonant filter 205' is connected between the first terminal of the second winding L8 of the transformer 206 and the load resistor R2. This load resistor R2 may be similar to the resistor associated with each electrode 3 of the electronic device 100.

[0192] Preferably, the second series resonant filter 205' is a bandpass filter configured to improve filtering of, for example, a 40kHz fundamental harmonic selected for another sinusoidal signal SW1.

[0193] In a preferred embodiment, the second series resonant filter 205' includes an inductor circuit portion 205A, which is connected in series with a capacitor circuit portion 205B. Both the inductor circuit portion 205A and the capacitor circuit portion 205B are connected between the first terminal of the second winding L8 of the transformer 206 and the load resistor R2.

[0194] According to an exemplary embodiment, the inductor circuit section 205A includes four inductors, specifically a first inductor L7, a second inductor L9, a third inductor L10, and a fourth inductor L11. The first and second inductors L7-L9 are connected in series to form a first inductor pair. The third and fourth inductors L10-L11 are connected in series to form a second inductor pair. The two inductor pairs L7-L9 and L10-L11 are connected in parallel.

[0195] Typical values ​​are L7 = L9 = L10 = L11 = 760 μH.

[0196] According to an alternative exemplary embodiment, the inductor circuit section 205A may include an inductor choke, such as a 750 microhenry inductor choke, configured to block signals with frequencies higher than a predetermined output frequency of the signal S. It should be understood that alternative or additional inductor circuit sections may be used in the second series resonant filter.

[0197] According to an exemplary embodiment, the capacitor circuit portion 205B of the second series resonant filter 205' includes a plurality of capacitors connected in series between the inductor circuit portion 205A and the load resistor R2, specifically... Figure 6 and Figure 9The seven capacitors shown in the example are, more specifically, the first capacitor C3, the second capacitor C4, the third capacitor C5, the fourth capacitor C6, the fifth capacitor C7, the sixth capacitor C8, and the seventh capacitor C9. The capacitor circuit portion providing the second series resonant filter 205' is particularly advantageous for filtering out low-frequency signals that could otherwise cause undesirable cardiac stimulation.

[0198] Typical values ​​are C3=C4=C5=C6=C7=C8=C9=1μF.

[0199] One related advantage of the embodiment including the amplifier circuit 203 with an emitter follower configuration is the low output impedance provided by this circuit. Specifically, this fact allows the output impedance of the H-bridge circuit 204 to be maintained at a low value to avoid "ringing" caused by the low-pass filter associated with the first series resonant filter 205.

[0200] In fact, if amplifier 203 is not used or the H-bridge circuit 204 is driven in an alternative manner, no device in the bridge will conduct, and no high impedance will be provided to transformer 206. This serves as an RF switch, as the high impedance can be seen when looking back at the output of that power module 202. In this way, safety functions are built into the circuit of the present invention, making safety an inherent property of the circuit. This contrasts with prior art solutions that typically require additional components specifically designed for safety functions.

[0201] Compared to the circuit solutions of power generators known in the art (e.g., power generators used in radio frequency ablation or RFA), power generators known in the art do not employ amplifier circuits with emitter follower configurations, because sufficient amplification is already achieved at the output transformer in these circuits.

[0202] Furthermore, square wave generators used in PFAs do not require low output impedance because square waves are never converted into sine waves, and "ringing" caused by low-pass filters is not a problem.

[0203] Figure 12 Show Figure 2 An alternative example of the circuit structure of one of the six power modules included in the power unit of a power generator. Figure 12 Similar parts are labeled accordingly where appropriate. It can be seen that this diagram provides information on... Figure 6 Examples of different implementation schemes. For example, Figure 12 The implementation scheme does not include a driver block containing one or more amplifier circuits, but instead receives bipolar input signals at the primary winding of the transformer. Figure 12 H-bridge 204 is targeted Figure 6In this embodiment, two power switching elements are used for each power switching element. This embodiment has been previously described in the specification.

[0204] The alternative to the first series resonant filter 205' is shown as comprising four parallel inductors connected in series with four parallel capacitors.

[0205] The alternative second series resonant filter 205 is shown as including an inductor choke instead. Figure 6 The inductor circuit section. This exemplary second series resonant filter 205” also includes a current measurement circuit 1201 and a voltage measurement circuit 1202. Providing one or both of the current measurement circuit 1201 and the voltage measurement circuit 1202 can be particularly advantageous because they allow direct measurement of the current, voltage, and / or power of the signal applied to the patient through one or more electrodes. This can be particularly contrasted with solutions that do not utilize the same isolation functionality provided by the embodiments herein. Providing more accurate measurement of one or all of the current, voltage, and power can be particularly advantageous for the safe monitoring of the patient and allows for improved control of the signal applied to the patient through one or more electrodes.

[0206] at last, Figure 12 The implementation clearly shows exemplary loads R2' and R2" representing the circuit used to provide signal S to the electrode".

[0207] This application also discloses a method for controlling multiple electrodes in an electronic device 100 for delivering coherent sinusoidal burst irreversible electroporation energy, wherein the device includes multiple electrodes 3 and a power generator 2.

[0208] The method includes the step of generating an electrical signal S by a power generator 2 for supplying electrical energy to each of the electrodes 3 of the plurality of electrodes. The electrical signal S is formed by alternating a first electrical signal S1 and a second electrical signal S2 over time. The first electrical signal S1 is a continuous bipolar signal comprising two or more fundamental sine waves SB within a first time interval T1, each fundamental sine wave consisting of a positive half-wave and a negative half-wave. The second electrical signal S2 has an amplitude equal to zero within a second time interval T2 following the first time interval T1.

[0209] The method further includes the following steps:

[0210] -During the first time interval T1, the first electrical signal S1 is supplied to electrode 3 of the plurality of electrodes;

[0211] -During the second time interval T2, the second electrical signal S2 is supplied to electrode 3 of the plurality of electrodes.

[0212] According to an alternative embodiment, the power generator 2 includes a single control unit 200 and a power unit 201 electrically connected to all of the plurality of electrodes 3. The method further includes the step of driving the power unit 201 by the single control unit 200:

[0213] - To change the number of basic sine waves SB that repeat within the first time interval T1, or

[0214] - To modify the power level by changing the duration of the second time interval T2.

[0215] The electrical energy level is associated with the signal S supplied to electrode 3.

[0216] According to an alternative implementation, the driving step includes:

[0217] - In order to generate the first electrical signal S1 of the electrical signal S

[0218] The first pulse signal PS1 and the second pulse signal PS2 supplied by the single control unit 200 to the power unit 201 are amplified. The first pulse signal PS1 includes a first square wave, and the second pulse signal PS2 includes a second square wave, which is 180 degrees out of phase with the first square wave.

[0219] - In order to generate the second electrical signal S2 of the electrical signal S, the single control unit 200 supplies signal zero to the power unit 201.

[0220] According to an alternative embodiment, in order to generate a first electrical signal S1 of the electrical signal S, the method further includes:

[0221] The first pulse signal PS1 and the second pulse signal PS2 are combined to generate a combined signal CS with a square waveform;

[0222] - A sine wave signal SW is generated by converting the square wave combination signal CS;

[0223] - Amplify the sinusoidal signal SW to generate another sinusoidal signal SW1;

[0224] The additional sinusoidal signal SW1 is filtered to generate a first electrical signal S1 to be supplied to electrode 3. According to an alternative embodiment, a method is provided for controlling a single electrode 3 in an electronic device 100 for delivering coherent sinusoidal burst-burst irreversible electroporation energy according to the invention, wherein the device includes a single electrode and a power generator 2.

[0225] refer to Figure 10A and Figure 10B Alternative embodiments of the electronic device 100 according to the present invention for delivering coherent sinusoidal burst irreversible electroporation energy or IRE to biological tissue 1 can be described.

[0226] Specifically, the electronic device 100 includes a first electrode 30 and a second electrode 31 that can be positioned on or near the biological tissue 1 to be treated, and a power generator 2. For example... Figure 10A As shown, the power generator 2 is configured to supply two in-phase sinusoidal electrical signals Va and Vb, specifically voltage signals, to the two electrodes 30 and 31, respectively. Figure 10B As shown, the power generator 2 is configured to supply two sinusoidal electrical signals Va and Vb that are “out of phase” (specifically, have a phase difference of 180 degrees) to the two electrodes 30 and 31, respectively.

[0227] For more details, see the reference. Figure 10A The power generator 2 is configured to deliver unipolar power to the tissue 1 for irreversible electroporation, the electrode power being driven by the voltage difference between the first electrode 30 and the second electrode 31 and the ground potential (0V) associated with the return electrode 5.

[0228] In this configuration, current flows from the first electrode 30 and the second electrode 31 to ground, i.e., to the return electrode 5. There is no voltage difference between the first electrode 30 and the second electrode 31 at any given time—therefore, no bipolar current flows.

[0229] When the voltage oscillates between the positive and negative peak values, current flows in and out of the ablation and return electrode 5.

[0230] refer to Figure 10B The power generator 2 of the present invention is configured to simultaneously deliver unipolar and bipolar power to tissue 1 for irreversible electroporation. In this case, a voltage is applied between each of the first electrode 30 and the second electrode 31 and between the ground potential (0V) associated with the return electrode 5 and through the same electrodes 30, 31.

[0231] These features of the electronic device 100 of the present invention can be specifically referred to. Figure 11 To illustrate, this figure schematically shows a plurality of electrodes 3 powered by a power generator 2 (not shown) of the present invention. These electrodes 3 are operatively associated with a catheter 4 that can be positioned on or near the myocardial tissue 1 to be treated.

[0232] In one embodiment, the power generator 2 of the present invention is configured to deliver a combination of bipolar and unipolar voltages to the electrodes 3. The unipolar voltage is either a voltage Va or a voltage Vb applied from each electrode 3 and the return electrode 5. The bipolar voltage (specifically, voltages Va-Vb) is applied between two adjacent electrodes 3.

[0233] In various embodiments, the power generator 2 of the present invention is configured to alternate between unipolar and bipolar voltage fields, for example by time-division multiplexing.

[0234] For example, the power generator 2 of the present invention uses 3500 volts delivered to each electrode 3 during the first time interval T1 of the aforementioned electrical signal S.

[0235] During the off period of electrical signal S, i.e. during the second time interval T2, the output of each power module 202 is disconnected from the corresponding electrode 3.

[0236] More specifically, the power generator 2 of the present invention is operable to deliver IRE energy according to a repeating sequence of three types of voltage deliveries.

[0237] In the case of unipolar voltage only: a voltage is applied from each electrode 3 to the patient circuit electrode 5; this first step is followed by a shutdown cycle.

[0238] In the case of a combination of unipolar and bipolar voltages: in the first step, a voltage is applied from each electrode 3 to the patient return electrode 5; this first step is followed by a second step, in which a voltage is applied across two adjacent electrodes; these two steps are followed by a shutdown cycle.

[0239] According to one implementation scheme, the ratio between bipolar and monopolar poles can be varied from 4:1 to all monopolar poles by selecting different combinations.

[0240] A full bipolar mode can be generated by disconnecting the return electrode 5 in the electronic device 100 and setting the phase shift of voltages Va and Vb to 180 degrees.

[0241] According to an alternative embodiment, one object of the present invention is to provide an electronic device 100 for delivering irreversible electroporation energy or IRE to a biological tissue 1 to be treated. The electronic device includes one or more electrodes 3 that can be positioned on or near the biological tissue 1 to be treated, and a power generator 2 for supplying electrical energy to the one or more electrodes 3; the power generator 2 is configured to generate an electrical signal S to energize the one or more electrodes 3.

[0242] The electrical signal S is formed by alternating between a first electrical signal S1 and a second electrical signal S2 over time; the first electrical signal S1 is supplied to one or more electrodes 3 during a first time interval T1, and the second electrical signal S2 is supplied to one or more electrodes during a second time interval T2 following the first time interval T1; the first electrical signal S1 has a periodic waveform in the first time interval T1; and the second electrical signal S2 has an amplitude equal to zero in the second time interval T2.

[0243] According to one implementation, the periodic waveform of the first electrical signal S1 has a frequency in the range of 25-49kHz.

[0244] According to the alternative implementation, the periodic waveform of the first electrical signal S1 has a frequency in the range of 40-60kHz.

[0245] According to another embodiment, the second time interval T2 of the second signal S2 has a duration from at least 1 millisecond to 1 second.

[0246] According to an alternative embodiment, a method for ablating biological tissue 1 is provided. The method involves steps using an electronic device 100 according to the invention for delivering coherent sinusoidal burst irreversible electroporation energy or IRE.

[0247] According to the alternative implementation, the biological tissue 1 to be ablated is selected from the group including: heart tissue, renal nerve, splenic nerve, tumor, and cancer cells.

[0248] According to an alternative embodiment, the electronic device 100 for delivering coherent sinusoidal burst irreversible electroporation energy or IRE includes a plurality of electrodes 3 positionable on or near the biological tissue 1 to be ablated, and a power generator 2 configured to generate an electrical signal S to energize each of the electrodes 3. The electrical signal S is formed by alternating a first electrical signal S1 and a second electrical signal S2 over time; the first electrical signal S1 is supplied to the electrodes 3 during a first time interval T1, and the second electrical signal S2 is supplied to the electrodes during a second time interval T2 following the first time interval T1; the first electrical signal S1 is a continuous bipolar signal comprising two or more fundamental sine waves SB within the first time interval T1, each fundamental sine wave consisting of a positive half-wave and a negative half-wave; the second electrical signal S2 has an amplitude equal to zero within the second time interval T2, thereby causing ablation of the biological tissue 1.

[0249] According to an alternative implementation, the first electrical signal S1 has a frequency in the range of 25-49 kHz or in the range of 40-60 kHz.

[0250] According to an alternative embodiment, a method for treating a patient's pathology is provided. The method involves performing ablation of the patient's biological tissue 1 using an electronic device 100 according to the invention for delivering coherent sinusoidal burst irreversible electroporation energy or IRE.

[0251] According to the alternative implementation scheme, the patient pathology is selected from the group including: hypertension, heart failure, and tumor.

[0252] According to an alternative implementation, the biological tissue 1 is selected from the group consisting of: heart tissue, renal nerve, splenic nerve, tumor, and cancer cells.

[0253] According to an alternative embodiment, a method is provided for ablating biological tissue 1 by delivering irreversible electroporation energy or IRE. The method involves applying an electrical signal S comprising at least a sinusoidal signal to the biological tissue 1.

[0254] According to a preferred embodiment, the electrical signal S is formed by alternating between a first electrical signal S1 and a second electrical signal S2 over time; the first electrical signal S1 is applied during a first time interval T1, and the second electrical signal S2 is applied during a second time interval T2 following the first time interval T1; the first electrical signal S1 is a continuous bipolar signal comprising two or more fundamental sine waves SB within the first time interval T1, each fundamental sine wave consisting of a positive half-wave and a negative half-wave; the second electrical signal S2 has an amplitude equal to zero within the second time interval T2, thereby causing ablation of the biological tissue 1.

[0255] According to another preferred embodiment, the first electrical signal S1 has a frequency in the range of 25-49 kHz or in the range of 40-60 kHz.

[0256] According to an alternative implementation, the biological tissue 1 is selected from the group consisting of: heart tissue, renal nerve, splenic nerve, tumor, and cancer cells.

[0257] According to an alternative embodiment, a method is provided for treating a patient's pathology by delivering irreversible electroporation energy or IRE. The method includes the step of applying an electrical signal S to the patient's biological tissue 1, the electrical signal S being formed by alternating a first electrical signal S1 and a second electrical signal S2 over time; the first electrical signal S1 is applied during a first time interval T1, and the second electrical signal S2 is applied during a second time interval T2 following the first time interval T1; the first electrical signal S1 is a continuous bipolar signal comprising two or more fundamental sine waves SB within the first time interval T1, each fundamental sine wave consisting of a positive half-wave and a negative half-wave; the second electrical signal S2 has an amplitude equal to zero within the second time interval T2, thereby causing ablation of the biological tissue 1.

[0258] According to a preferred embodiment, the first electrical signal S1 has a frequency in the range of 25-49 kHz or in the range of 40-60 kHz.

[0259] According to the alternative implementation scheme, the patient pathology is selected from the group including: hypertension, heart failure, and tumor.

[0260] The electronic device 100 of the present invention provides additional related advantages.

[0261] Specifically, the power generator 2, configured to generate a first electrical signal S1 comprising a fundamental sine wave SB, relies on a transformer, specifically transformer 206 and a first transformer circuit 230. This ensures a high level of electrical isolation for the patient.

[0262] Furthermore, the electronic device 100 of the present invention ensures a high degree of flexibility in energy delivery by modifying the number of fundamental sine waves SB of the first electrical signal S1, the peak-to-peak amplitude of these sine waves, and the duration of the second time interval T2. Therefore, the length and depth of lesions induced by the IRE procedure can be customized.

[0263] The electrodes that deliver sine waves can be switched on, off, or in any state within a range of 0 to 360 degrees out of phase.

[0264] Furthermore, the applicant has demonstrated that the cost of designing and manufacturing the components for the power generator 2 used to generate sine waves is significantly lower than the cost of manufacturing square wave power generators known in the art.

[0265] List of icon numbers

[0266] 100 electronic devices

[0267] 1 biological tissue

[0268] 2 power generators

[0269] 3 electrodes

[0270] 30 First Electrode

[0271] 31 Second Electrode

[0272] 4 catheters

[0273] 5. Another electrode, return electrode

[0274] 6 return wires

[0275] 7 wires

[0276] S electrical signal

[0277] S1 First Electrical Signal

[0278] S2 Second Electrical Signal

[0279] T1 First time interval

[0280] T2 Second time interval

[0281] SB basic sine wave

[0282] 200 single control units

[0283] 201 power unit

[0284] 202 Power Module

[0285] 203 Driver Circuit Block—Amplifier Circuit with Emitter Follower Configuration

[0286] 204 Selector Block—H-Bridge Circuit—Power Inverter Block

[0287] 205 First Series Resonant Filter

[0288] 206 Electrical Isolator Block—Transformer

[0289] 205' Second Series Resonant Filter

[0290] 207 microprocessor

[0291] 208 Variable High Voltage Power Supply Block

[0292] 209 Programmable Logic Controller Block

[0293] 210 video interface block

[0294] 210' button block

[0295] 211 Watchdog Block

[0296] 212 audio interface block

[0297] 230 First Transformer Circuit

[0298] Vcc supply voltage signal — First DC power supply voltage

[0299] Vcc1 supply voltage signal — second DC power supply voltage

[0300] GND grounding potential

[0301] PS1 first pulse signal

[0302] PS2 second pulse signal

[0303] CS combined signal

[0304] SW sine wave signal

[0305] Another sine wave signal from SW1

[0306] 203' First Amplifier Circuit

[0307] 203” Second Amplifier Circuit

[0308] M7 first MOSFET transistor

[0309] R1 is the first resistor.

[0310] Q1, Q3 First BJT transistor

[0311] Q2, Q4 second BJT transistors

[0312] M8 second MOSFET transistor

[0313] R4, the second resistor

[0314] The first output terminal of the OU1 first amplifier circuit 203'

[0315] OU2 Second Amplifier Circuit 203” Second Output Terminal

[0316] 207 First Transformer Circuit

[0317] L1 primary winding

[0318] L2 primary winding

[0319] L3 secondary winding

[0320] L4 third stage winding

[0321] L5 fourth secondary winding

[0322] Drive section of 204'H bridge inverter

[0323] Power section of the 204” H-bridge inverter

[0324] B1 First Inverter Branch

[0325] B2 Second Inverter Branch

[0326] M1 First Power Mosfet

[0327] M2 secondary power Mosfet

[0328] M3 third power MOSFET

[0329] M4 fourth power MOSFET

[0330] R5 is the resistor for the second DC power supply voltage.

[0331] O1 First Output Terminal

[0332] O2 Second Output Terminal

[0333] R8 third resistor

[0334] D2 First Diode

[0335] R11 Fourth Resistor

[0336] R3, the fifth resistor

[0337] R13 sixth resistor

[0338] D4 Second Diode

[0339] R9 Seventh Resistor

[0340] R10 eighth resistor

[0341] D1 Third Diode

[0342] R7 Ninth Resistor

[0343] R12, the tenth resistor

[0344] D3 Fourth Diode

[0345] R6 Output Resistor

[0346] The first winding of L6 transformer 206

[0347] L8 transformer 206 secondary winding

[0348] L14 Inductor

[0349] C1 capacitor

[0350] R2 load resistor

[0351] 205A Inductor Circuit Section

[0352] 205B capacitor circuit section

[0353] L7 First Inductor

[0354] L9 Second Inductor

[0355] L10 Third Inductor

[0356] L11 Fourth Inductor

[0357] C3 First Capacitor

[0358] C4 is the second capacitor.

[0359] C5 Third Capacitor

[0360] C6 Fourth Capacitor

[0361] C7 Fifth Capacitor

[0362] C8 sixth capacitor

[0363] C9 Seventh Capacitor

[0364] C2, C10 protection capacitors

[0365] Va, Vb sinusoidal electrical signals

[0366] 2021 First Power Module

[0367] 2022 Second Power Module

[0368] 2023 Third Power Module

[0369] 2024 Fourth Power Module

[0370] 2025 Fifth Power Module

[0371] 2026 Sixth Power Module.

Claims

1. A power unit for supplying electrical power to at least one electrode of an electronic device for delivering coherent sinusoidal burst irreversible electroporation energy, the power unit comprising at least one power module configured to generate an electrical signal (S) to energize one or more corresponding electrodes, each of the at least one power module comprising: A selection block configured to receive at least one square wave input signal, wherein the selection block is configured to continuously change the power level associated with the electrical signal (S) based on the at least one square wave input signal to provide a combined signal at the output of the selection block, and wherein the combined signal comprises a square wave waveform, wherein the selection block includes an H-bridge circuit and a charging capacitor having a first node coupled between a power supply terminal that can be coupled to a second power supply voltage source and a ground terminal that can be coupled to ground, wherein the charging capacitor is configured to selectively discharge through the H-bridge circuit based on the at least one square wave input signal, and wherein the selective discharge of the charging capacitor is configured to provide the combined signal at the output of the selection block; as well as A filter and an electrical isolation block is configured to convert the combined signal into a sine wave signal and filter the sine wave signal to generate the electrical signal (S), wherein the conversion and the filtering are electrically isolated from each other.

2. The power unit as claimed in claim 1, wherein the H-bridge circuit comprises: The first inverter branch includes a first power switching element and a second power switching element. The second inverter branch includes a third power switching element and a fourth power switching element. The first power switching element and the third power switching element are respectively connected between the power supply terminal that can be coupled to the second power supply voltage and the first output terminal and the second output terminal of the H-bridge circuit; The second power switching element and the fourth power switching element are connected between the first output terminal and the second output terminal of the H-bridge circuit and the ground terminal that can be coupled to ground.

3. The power unit of claim 2, wherein the gate terminal of each of the first power switching element, the second power switching element, the third power switching element and the fourth power switching element is controlled in response to the at least one square wave input signal to provide a continuous variation of the power level associated with the electrical signal (S).

4. The power unit of claim 1, wherein the filter and electrical isolation block comprises at least one of the following: A first series resonant filter is configured to generate the sine wave signal by transforming the combined signal at the output of the selection block; A step-up transformer, configured to amplify the sinusoidal signal to generate another sinusoidal signal to provide the electrical isolation; as well as A second series resonant filter is configured to provide filtering of the other sine wave in order to generate the electrical signal to be supplied to the electrode.

5. The power unit of claim 4, wherein the first series resonant filter includes a bandpass filter configured to convert the combined signal into the sinusoidal signal at a predetermined frequency.

6. The power unit of claim 4, wherein the step-up transformer comprises a step-up transformer having a high-frequency ferrite core.

7. The power unit of claim 4, wherein the second series resonant filter comprises one or both of the following: An inductor choke, wherein the inductor choke is configured to filter frequencies above a predetermined frequency; and At least one filter capacitor, wherein the filter capacitor is configured to filter frequencies below the predetermined frequency.

8. The power unit of claim 1, wherein the filtering and isolation block further comprises one or both of the following: A current measurement circuit configured to measure the current of the electrical signal (S); and A voltage measurement circuit configured to measure the voltage of the electrical signal (S).

9. The power unit of claim 1, further comprising a drive circuit configured to receive a first drive signal (PS1) and a second drive signal (PS2), wherein the drive circuit is configured to amplify the first drive signal and the second drive signal to provide a first square wave input signal and a second square wave input signal to the selection block.

10. The power unit of claim 9, further comprising a transformer circuit disposed between the drive circuit and the selection block, wherein the transformer circuit is configured to provide electrical isolation between the drive circuit and the selection block.

11. The power unit of claim 10, wherein the transformer circuit includes a primary winding having a first terminal coupled to a first output terminal of the drive circuit and a second terminal coupled to a second output terminal of the drive circuit, and the transformer further includes a primary winding, a secondary winding, a tertiary winding and a fourth secondary winding.

12. The power unit of claim 11, wherein the first drive signal and the second drive signal are different signals, and the first drive signal and the second drive signal are provided to the drive circuit such that the first square wave input signal and the second square wave input signal are not simultaneously provided to the transformer circuit.

13. The power unit of claim 11, wherein each of the first secondary winding, the second secondary winding, the third secondary winding, and the fourth secondary winding is coupled to a corresponding one of the first power switching element, the second power switching element, the third power switching element, and the fourth power switching element of the H-bridge circuit, such that the first square wave input signal and the second square wave input signal provide control over the first power switching element, the second power switching element, the third power switching element, and the fourth power switching element.

14. A power unit for supplying electrical power to at least one electrode of an electronic device for delivering coherent sinusoidal pulse irreversible electroporation energy, the power unit comprising at least one power module configured to generate an electrical signal (S) to energize one or more corresponding electrodes, each of the at least one power module comprising: A selection block is configured to receive at least one square wave input signal, wherein the selection block is configured to continuously change the power level associated with the electrical signal (S) based on the at least one square wave input signal in order to provide a combined signal at the output of the selection block, and wherein the combined signal comprises a square wave waveform. as well as A filtering and electrical isolation block is configured to convert the combined signal into a sinusoidal signal and filter the sinusoidal signal to generate the electrical signal (S), wherein the conversion and the filtering are electrically isolated from each other, and wherein the filtering and electrical isolation block includes at least one of the following: A first series resonant filter is configured to generate the sine wave signal by transforming the combined signal at the output of the selection block; A step-up transformer, configured to provide electrical isolation by amplifying the sinusoidal signal to generate another sinusoidal signal; and A second series resonant filter is configured to provide filtering of the other sine wave in order to generate the electrical signal to be supplied to the electrode.

15. A power unit for supplying electrical power to at least one electrode of an electronic device for delivering coherent sinusoidal pulse irreversible electroporation energy, the power unit comprising at least one power module configured to generate an electrical signal (S) to energize one or more corresponding electrodes, each of the at least one power module comprising: A selection block is configured to receive at least one square wave input signal, wherein the selection block is configured to continuously change the power level associated with the electrical signal (S) based on the at least one square wave input signal in order to provide a combined signal at the output of the selection block, and wherein the combined signal comprises a square wave waveform. as well as A filtering and electrical isolation block is configured to convert the combined signal into a sinusoidal signal and filter the sinusoidal signal to generate the electrical signal (S), wherein the conversion and the filtering are electrically isolated from each other, and wherein the filtering and isolation block further includes one or both of the following: A current measurement circuit configured to measure the current of the electrical signal (S); as well as A voltage measurement circuit configured to measure the voltage of the electrical signal (S).

16. A power unit for supplying electrical power to at least one electrode of an electronic device for delivering coherent sinusoidal pulse irreversible electroporation energy, the power unit comprising at least one power module configured to generate an electrical signal (S) to energize one or more corresponding electrodes, each of the at least one power module comprising: A selection block is configured to receive at least one square wave input signal, wherein the selection block is configured to continuously change the power level associated with the electrical signal (S) based on the at least one square wave input signal in order to provide a combined signal at the output of the selection block, and wherein the combined signal comprises a square wave waveform. A filter and an electrical isolation block, the filter and the electrical isolation block being configured to convert the combined signal into a sine wave signal and filter the sine wave signal to generate the electrical signal (S), wherein the conversion and the filtering are electrically isolated from each other; as well as A driving circuit configured to receive a first driving signal (PS1) and a second driving signal (PS2), wherein the driving circuit is configured to amplify the first driving signal and the second driving signal to provide a first square wave input signal and a second square wave input signal to the selection block.

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