Electronic device for delivering coherent sinusoidal pulse group irreversible electroporation energy to biological tissue

Abstract

The present invention relates to an electronic device (100) for delivering coherent sinusoidal pulse group irreversible electroporation energy to a biological tissue (1) to be treated. The electronic device comprises at least one electrode (3) positionable on or near the biological tissue (1) to be treated. The electronic device (100) further comprises a generator (2) for supplying electrical energy to the or each electrode (3) and more particularly configured to generate a respective electrical signal (S) to energize the or each individual electrode (3). The or each electrical signal (S) is formed by alternating in time a first electrical signal (SI) with a second electrical signal (S2), each first electrical signal (SI) being identical. The first electrical signal (SI) is supplied to an individual electrode (3) during a first time interval (T1) and the second electrical signal (S2) is supplied to the individual electrode (3) during a second time interval (T2) after the first time interval (T1). The first electrical signal (SI) is a continuous bipolar signal in the first time interval (T1) comprising two or more elementary sinusoidal waves (SB). Each elementary sinusoidal wave has an average peak-to-peak amplitude in the range of 2,000 V to 20,000 V and consists of one positive half wave and one negative half wave, wherein each half wave has the same width. The first electrical signal (SI) further has a frequency in the range of 25 kHz to 75 kHz. At the same time, the second electrical signal (S2) has an amplitude equal to zero in the second time interval (T2).

Description

Technical Field

[0001] The present invention generally relates to an electronic device for delivering coherent sinusoidal pulse group irreversible electroporation energy to biological tissue, a method for controlling at least one electrode in such a device, and a method for ablating biological tissue in a patient using at least one electrode of such a device. Background Technology

[0002] Tissue ablation is used to treat patients in many medical procedures. Ablation can be performed to remove or denature unwanted tissue, such as diseased heart cells. Ablation can be achieved by passing energy, such as electrical energy, through one or more electrodes, causing tissue death at the electrode contact point. Ablation procedures can be performed on patients with any arrhythmia, such as atrial fibrillation (AF), by ablating heart tissue.

[0003] Radiofrequency ablation (RFA) is a medical procedure in which heat generated by intermediate-frequency alternating current (e.g., in the range of 350 to 500 kHz) is used to ablate portions of the conductive system of the heart, tumors, or other dysfunctional tissues.

[0004] Specifically, in this process, 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, when the energy delivery device is placed on the tissue surface, inductive thermal ablation, such as RFA, can be used to effectively and continuously ablate tissue sites locally. Although RFA can effectively ablate large amounts of target tissue, this technique has limitations. A frequently mentioned issue when using this procedure during cardiac ablation involves the heat sink; one aspect of the process may involve blood flow, and the heat generated on the ablation element will be removed / dissipated by the cooler blood flow around the element. This heat dissipation effect can alter the shape and maximum volume of the ablated tissue.

[0005] 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 for short periods (microseconds or nanoseconds), resulting in electroporation of cells and tissues. Electroporation is the process by which the applied electric field (i.e., the PEF) causes pores to form in the cell membrane. The formation of these pores leads to permeation, which can be reversible or irreversible depending on the parameters of the applied PEF.

[0006] In reversible electroporation, cells remain viable, which is fundamental to electrochemical therapy and gene electrotransfer. Conversely, in irreversible electroporation (IRE), cells and tissues cannot survive due to the activation of a programmed cell death cascade.

[0007] IRE is an effective treatment for solid tumors. However, given the limitations of current heat-based methods, IRE may also be useful in cardiology, particularly for cardiac ablation.

[0008] When used to ablate cardiac tissue, irreversible electroporation (IRE) involves applying electrical pulses to the target tissue in the range of microseconds to milliseconds, which causes nanoscale nonthermal defects to be generated in the cell membrane. These defects disrupt cell membrane homeostasis, leading to irreversible cell membrane permeability and inducing cell necrosis without raising the temperature of the tissue ablation zone.

[0009] Typical PEF parameters leading to IRE include 10 to 90 pulses, pulse lengths of microseconds or nanoseconds (typically 100 μs), frequencies of 1 to 10 Hz, and electric fields between 500 V / cm and 3000 V / cm. (See Elad Maor et al., “Pulsed electric fields for cardiac ablation and beyond: A state-of-the-art review,” Heart Rhythm 2019; 16: 1112-1120).

[0010] One challenge in designing PEF protocols is isolating the effects of the electric field on biological tissue. According to Joule's first law, an electric field applied to tissue generates heat, stating that the heating power is proportional to the square of the resistance and the current. To overcome this problem and obtain electroporation lesions independently, most PEF protocols use ultrashort pulses (microseconds) at low frequencies (1 to 10 Hz). This balances the heating with the cooling effects of physiological heat conduction and convection, thus preventing a significant temperature rise.

[0011] 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 during each pulse. However, receiving anesthetics is undesirable for patients and may prevent them from seeking electroporation-based therapies.

[0012] The use of electronic systems to deliver irreversible electroporation (IRE) energy to biological tissues is known in the art, wherein these electronic systems are configured to generate high-frequency bipolar waveforms to reduce muscle contraction during electroporation-based therapies.

[0013] In particular, high-frequency IRE (H-FIRE) is a technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed using monopolar electrical pulses. In fact, no visual or tactile evidence of muscle contraction is observed during H-FIRE at 250 kHz or 500 kHz. Therefore, H-FIRE can be performed clinically without the administration of numbing agents.

[0014] H-FIRE can be used in applications involving square wave electrical signals. For this purpose, it is known, for example, to use a square wave signal centered at 500 kHz.

[0015] However, rectangular waveforms contain signal components with varying frequencies and amplitudes, which can have dangerous effects when an IRE is used specifically to treat cardiac tissue. For example, a conventional IRE square wave signal has a 150Hz component at around 6V, posing a significant risk of cardiac stimulation.

[0016] The problem with square-wave pulsed electric fields is similar to that of ICDs (intrinsic cardioverter defibrillators): these types of devices cause severe cardiac tissue damage upon discharge. Using square-wave pulsed electric fields can lead to cardiac tissue damage outside the desired area. Therefore, sedation is required, and the square-wave delivery must be synchronized with the R wave of the ECG.

[0017] Therefore, there remains a strong need to provide treatments for biological tissues, especially cardiac tissues, based on irreversible electroporation (IRE), which avoids myocardial stimulation and does not require sedation of the patient. Summary of the Invention

[0018] The objective of this invention is to provide an electronic device for delivering irreversible electroporation (IRE) energy (particularly coherent sinusoidal pulse group IRE) to biological tissues (particularly cardiac tissues) to be treated, said electronic device having, for example, structural and functional features that satisfy the above-mentioned requirements and overcome the disadvantages mentioned above in prior art electronic systems for the same purpose.

[0019] These and other objectives will be achieved by the electronic device according to claim 1.

[0020] In particular, according to a first aspect of the invention, an electronic device is provided for delivering coherent sinusoidal pulse group irreversible electroporation energy or IRE to biological tissue (particularly cardiac tissue) to be treated.

[0021] The electronic device includes:

[0022] At least one electrode that can be positioned on or near the biological tissue to be treated; and a generator for supplying electrical energy to the electrode or each of the electrodes.

[0023] The generator is configured to generate corresponding electrical signals to excite the electrodes.

[0024] The electrical signals are formed by alternating between a first electrical signal and a second electrical signal over time, with each first electrical signal being identical. The first electrical signal is supplied to a single electrode during a first time interval, and the second electrical signal is supplied to the same single electrode during a second time interval following the first time interval. The first electrical signal is a continuous bipolar signal comprising two or more fundamental sine waves in the first time interval, each fundamental sine wave having a peak-to-peak average amplitude in the range of 2,000V to 20,000V and consisting of a positive half-wave and a negative half-wave, each half-wave having the same width. The first electrical signal has a frequency in the range of 25kHz to 75kHz. The second electrical signal has an amplitude equal to zero in the second time interval.

[0025] The applicant has demonstrated that an electrical signal S generated by alternating over time a first electrical signal comprising two or more fundamental sine waves with a second electrical signal having an amplitude of zero does not produce myocardial stimulation. Therefore, in the first respect, the patient does not need to be sedated. In a further respect, energy delivery does not need to be synchronized with the cardiac R wave of the ECG.

[0026] In addition, providing a first electrical signal with a frequency in the range of 25 kHz to 75 kHz ideally imparts sufficient energy to cause irreversible tissue ablation as needed, while continuing to avoid myocardial stimulation.

[0027] Preferably, the first electrical signal has a frequency in the range of 35 kHz to 65 kHz.

[0028] The first electrical signal may have a frequency in the range of 40 kHz to 60 kHz.

[0029] Optionally, the first electrical signal has a frequency in the range of 45 kHz to 55 kHz.

[0030] This frequency range is advantageous for delivering sufficient energy while avoiding myocardial stimulation.

[0031] Preferably, the first electrical signal comprises two to fifteen fundamental sine waves in the first time interval.

[0032] Optionally, the second time interval of the second signal has a duration of at least 1 millisecond to 1 second.

[0033] These features ideally result in irreversible ablation while keeping any associated thermal energy generation to a minimum.

[0034] Preferably, the electronic device includes a plurality of electrodes, and the generator includes a single control unit and a power unit for generating the corresponding electrical signal, and the power unit is electrically connected to all of the plurality of electrodes, wherein the plurality of electrodes thereby provide one of a unipolar voltage, a bipolar voltage, or a combination of a bipolar voltage and a unipolar voltage.

[0035] This arrangement offers options for achieving: relatively deep irreversible ablation into biological tissue, for example by providing unipolar voltages to the electrodes; and shallower, more localized irreversible ablation within such tissue, for example by providing bipolar voltages to the electrodes. Additionally, a combination of bipolar and unipolar voltages provides the option for achieving relatively deep irreversible ablation, similar to ablation achieved using unipolar voltage alone, but with less muscle stimulation compared to using the same amount of unipolar voltage alone.

[0036] Furthermore, this irreversible ablation is achieved by generating a voltage field, that is, extending away from the electrode in the case of a unipolar voltage and between adjacent electrodes in the case of a bipolar voltage (or a combination of these voltage fields in the case of a combination of unipolar and bipolar voltages), thus resulting in electroporation, that is, increasing the permeability of cell membranes within biological tissues, thereby avoiding the generation of heat within such tissues, for example, if an electric current were instead passed through the tissue.

[0037] Optionally, in the presence of an electrical return path, the power unit is configured to supply the same separate electrical signal to each electrode so that the electrode provides a unipolar voltage via the electrical return path.

[0038] In the absence of an electrical return path, the power unit can be configured to supply separate electrical signals 180° out of phase with each other to adjacent electrodes so that the electrodes provide bipolar voltages.

[0039] This type of arrangement advantageously provides the required unipolar or bipolar voltage in an easy-to-implement manner.

[0040] In a preferred embodiment of the invention, where an electrical return path exists, the power unit is configured such that adjacent electrodes supply separate electrical signals that are out of phase with each other, so that the electrodes provide a combination of bipolar and unipolar voltages.

[0041] Providing the electrodes with a combination of bipolar and unipolar voltages in this manner (i.e., in the presence of an electrical return path) means that most electrical returns occur between adjacent electrodes, while some electrical returns still occur via the electrical return path (i.e., externally). This is therefore a practical method to help achieve relatively deep irreversible ablation, similar to ablation achieved using unipolar voltage alone, but with less muscle stimulation compared to using the same amount of unipolar voltage alone.

[0042] In another preferred embodiment of the invention, the power unit is configured to change the degree to which the individual electrical signals supplied to adjacent electrodes are out of phase with each other.

[0043] Preferably, the power unit is configured such that the degree to which the individual electrical signals supplied to adjacent electrodes are out of phase with each other varies between 0° and 180°.

[0044] This variation in the degree to which the individual electrical signals supplied to adjacent electrodes are out of phase with each other ideally allows for alteration of the depth of irreversible ablation.

[0045] According to a second aspect of the invention, a method is provided for controlling at least one electrode in an electronic device for delivering coherent sinusoidal pulse group irreversible electroporation energy to a biological tissue to be treated, the electronic device comprising at least one electrode positionable on or near the biological tissue to be treated, and a generator for supplying electrical energy to said or each electrode, the generator being configured to generate a corresponding electrical signal to excite said or each electrode; and the method comprising the following steps:

[0046] The first electrical signal (S1) and the second electrical signal (S2) are alternated over time to form the signal (S1) or each electrical signal (S), wherein each first electrical signal (S1) is the same.

[0047] A first electrical signal (S1) is supplied to the individual electrode (3) during a first time interval (T1) and a second electrical signal (S2) is supplied to the individual electrode (3) during a second time interval (T2) following the first time interval (T1).

[0048] 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 has a peak-to-peak average amplitude in the range of 2,000V to 20,000V and consists of a positive half-wave and a negative half-wave, each half-wave having the same width. The first electrical signal (S1) has a frequency in the range of 25kHz to 75kHz.

[0049] The second electrical signal (S2) has an amplitude that is equal to zero in a second time interval (T2) following the first time interval (T1).

[0050] According to a second aspect of the invention, a method is provided for ablating biological tissue in a patient using at least one electrode of an electronic device for delivering coherent sinusoidal pulse-group irreversible electroporation energy to the biological tissue to be treated, the electronic device comprising at least one electrode and a generator for supplying electrical energy to the electrode, the generator being configured to generate a corresponding electrical signal to excite the electrode.

[0051] The method includes the following steps:

[0052] Position the electrode (3) on or near the biological tissue (1) to be treated;

[0053] The first electrical signal (S1) and the second electrical signal (S2) are alternated over time to form the signal (S1) or each electrical signal (S2), wherein each first electrical signal (S1) is the same.

[0054] The first electrical signal (S1) is supplied to the individual electrode (3) during the first time interval (T1) and the second electrical signal (S2) is supplied to the individual electrode (3) during the second time interval (T2) following the first time interval (T1).

[0055] 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 has a peak-to-peak average amplitude in the range of 2,000V to 20,000V and consists of a positive half-wave and a negative half-wave, each half-wave having the same width. The first electrical signal (S1) has a frequency in the range of 25kHz to 75kHz.

[0056] The second electrical signal (S2) has an amplitude that is equal to zero in a second time interval (T2) following the first time interval (T1).

[0057] The method of the present invention shares the benefits associated with the corresponding features of the electronic device of the present invention. Attached Figure Description

[0058] Other features and advantages of the invention will become apparent from the description of exemplary embodiments given below by way of non-limiting example with reference to the accompanying drawings, in which:

[0059] - Figure 1An electronic device for delivering coherent sinusoidal pulse group irreversible electroporation energy or IRE to biological tissue according to a first embodiment of the present invention is illustrated, wherein the electronic device includes a plurality of electrodes that can be positioned on or near the biological tissue to be treated, and a generator for supplying electrical energy to each of the electrodes.

[0060] - Figure 2 A block diagram is used to illustrate Figure 1 A generator for electronic devices, the generator comprising a single control unit and a power unit;

[0061] - Figure 3 The graph shows the change over time. Figure 1 Example 2: A generator produces an electrical signal by alternating between a first electrical signal and a second electrical signal over time.

[0062] - Figure 4 Displayed at a higher resolution Figure 3 The diagram represents a portion of the first electrical signal;

[0063] - Figure 5 The diagram shows the Fourier analysis of the first electrical signal of eleven basic 50kHz sine waves;

[0064] - Figure 6 An electronic device according to a first embodiment of the invention is schematically shown, wherein the generator is configured to supply “in-phase” sinusoidal electrical signals to adjacent electrodes respectively, such that the electrodes provide unipolar voltages;

[0065] - Figure 7 The illustration is by Figure 6 The electric field generated by the arrangement;

[0066] - Figure 8 An electronic device according to a first embodiment of the invention is schematically shown, wherein the generator is configured to supply “out-of-phase” sinusoidal electrical signals to adjacent electrodes, such that the electrodes provide bipolar voltages;

[0067] - Figure 9 The illustration is by Figure 8 The electric field generated by the arrangement;

[0068] - Figure 10 An electronic device according to a first embodiment of the invention is schematically shown, wherein, in the presence of an electrical return path, the generator is configured to supply “out-of-phase” sinusoidal electrical signals to adjacent electrodes respectively, such that the electrodes provide a combination of bipolar and unipolar voltages.

[0069] - Figure 11 The illustration is by Figure 10 The electric field generated by the arrangement.

[0070] Identical or similar components are represented by the same labels in the diagram. Detailed Implementation

[0071] The invention will be more readily understood by referring to the following detailed description, examples, drawings, and their preceding and following descriptions. However, before disclosing and describing the apparatuses, systems, and / or methods of the invention, it will be understood that, unless otherwise specified, the invention is not limited to the specific apparatuses, systems, and / or methods disclosed, as they can certainly be modified. It will also be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.

[0072] The following description of the invention is provided as a practical teaching of the best currently known embodiments of the invention. 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 understood 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 may even be desirable and part of the invention.

[0073] According to the general implementation plan, refer to Figure 1 The electronic device according to the invention for delivering coherent sinusoidal pulse group irreversible electroporation energy or IRE to the biological tissue 1 to be treated is generally indicated by reference numeral 100.

[0074] 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 generator 2 for supplying electrical energy to each of the electrodes 3. More specifically, in Figure 1 The example illustrates six electrodes 3, each operatively associated with a catheter 4. Other embodiments of the invention may include fewer or more than six electrodes.

[0075] In a preferred embodiment, the biological tissue 1 to be treated is heart tissue.

[0076] The generator 2 is specifically connected to the electrode 3 by six wires 7 and is configured to generate a corresponding electrical signal S to excite each individual electrode 3, so that the electrodes together apply a voltage electric field to the biological tissue 1.

[0077] Additionally, the electronic device 100 includes another electrode 5, which acts as a return electrode for the voltage and electric field applied to the biological tissue 1, i.e., an electrical return path. More specifically, this return electrode 5 or backplane is electrically connected to the generator 2 via a corresponding return line 6.

[0078] 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 generator 2 is electrically connected to this single electrode 3 and is configured to generate an electrical signal S to excite the electrode 3, i.e., to apply a voltage electric field to the biological tissue 1 through the single electrode 3.

[0079] 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. For example... Figure 3 As shown, each first electrical signal S1 is identical. The first electrical signal S1 is supplied to a single electrode 3 during the first time interval T1, and the second electrical signal S2 is supplied to the same single electrode 3 during the second time interval T2 after the first time interval T1.

[0080] 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 consists of a positive half-wave and a negative half-wave, wherein each half-wave has the same width, such as, for example... Figure 4 As shown. The second electrical signal S2 has an amplitude that is equal to zero during the second time interval T2.

[0081] For example, Figure 3 The electrical signal S depicted includes three first electrical signals S1, wherein two of the first electrical signals S1 are separated from each other by a second electrical signal S2 that is empty in the second time interval T2.

[0082] In an alternative implementation, the first electrical signal S1 includes two or more fundamental sine waves SB that are repeated during the first time interval T1.

[0083] Regarding this invention, the applicant proposes using an electrical signal S to ablate tissue 1. The electrical signal S consists of several sinusoidal pulse groups (i.e., multiple first electrical signals S1) spaced apart during a cooling cycle (i.e., a second electrical signal S2, where no electrical energy is transmitted to the electrode 3). The sinusoidal pulse groups are generated in a manner that avoids stimulating the heart, even when applied for a relatively long 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.

[0084] In more detail, Figure 3 The diagram of the electrical signal S shown includes three sinusoidal pulse groups, each pulse group spaced 1.5 milliseconds apart by a cooling cycle.

[0085] exist Figure 5The diagram depicts a Fourier analysis of a first electrical signal S1 comprising eleven fundamental sine waves SB, for example, at 50 kHz. Specifically, this Fourier analysis shows that the voltage amplitude of the 50 kHz signal component, the desired component, is 67 dB higher than that of the 150 Hz signal component (the harmful component). In particular, 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, a near-zero peak voltage that would not cause cardiac stimulation.

[0086] In contrast, traditional IRE square wave signals have a 150Hz signal component at a voltage of around 6V, which poses a significant risk of cardiac stimulation.

[0087] Therefore, in the first embodiment shown, the first electrical signal S1 has a frequency in the range of 25 kHz to 75 kHz.

[0088] Preferably, the first electrical signal S1 has a frequency in the range of 35 kHz to 65 kHz, more preferably 40 kHz to 60 kHz, and most preferably 45 kHz to 55 kHz. More particularly, the first electrical signal S1 may have a frequency of 50 kHz.

[0089] The first electrical signal S1 may include two to fifteen basic sine waves SB in the first time interval T1.

[0090] In practice, depending on the tissue ablation requirements, when a higher voltage is applied to tissue 1 with electrical signal S, generator 2 provides a first electrical signal S1 comprising fewer cycles of the fundamental sine wave SB repeated in 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 a lower voltage is applied to tissue 1 with electrical signal S, generator 2 provides a first electrical signal S1 comprising more cycles of the fundamental sine wave SB repeated in the first time interval, i.e., more cycles of the first electrical signal S1 and the second electrical signal S2 are required. Therefore, a voltage applied to tissue 1 with 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 in the first time interval T1.

[0091] The second time interval T2 (i.e., the cooling period) of the second signal S2 has a duration of at least 1 millisecond to 1 second.

[0092] In particular, the duration of the second time interval T2 can be changed based on heat dissipation requirements.

[0093] The peak-to-peak average amplitude of each fundamental sine wave SB ranges from 2,000V to 20,000V. The preferred values ​​depend on the organization. In particular, when generator 2 is energized, the initial settings can be -2.5kV and +2.5kV, and then changed to suit various organizational requirements.

[0094] Generally speaking, according to the present invention, the properties of the electrical signal S can be changed as long as the amplitude of the signal component below 200Hz is negligible.

[0095] Meanwhile, the 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. In this way, the plurality of electrodes 3 are capable of providing (i) a unipolar voltage, (ii) a bipolar voltage, or (iii) a combination of a bipolar voltage and a unipolar voltage.

[0096] More specifically, 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.

[0097] For example, such as Figure 2 As schematically shown, the power module 202 includes one or more of the following:

[0098] - Drive circuit block 203, which is controlled by a single control unit 200 to generate the first electrical signal S1 or the second electrical signal S2 respectively from drive signals PS1, PS2 or an empty signal provided by the single control unit 200;

[0099] - 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; and

[0100] - Filtering and electrical isolation blocks 205, 206, 205′.

[0101] exist Figure 2 In one example, the power unit 201 includes six power modules 202. Each power module 202 is configured to generate a corresponding electrical signal S and supply the electrical signal to a separate electrode 3. More specifically, refer to Figure 2 From top to bottom, power unit 201 includes a first power module 2021, a second power module 2022, a third power module 2023, a fourth power module 2024, a fifth power module 2025, and a sixth power module 2026. The return connections of all power modules 2021 to 2026 are connected together and correspond to return line 6, i.e., a single electrical return path.

[0102] refer to Figure 6 In the presence of an electrical return path (i.e., return electrode 5 and associated return line 6), the power unit 201 is configured to supply the same individual electrical signal S to each electrode 3, i.e., the same waveform that is in phase with each other, so that the electrode 3 provides a unipolar voltage via the electrical return path.

[0103] More specifically, generator 2 is configured to supply the same sinusoidal electrical signals Va and Vb, respectively, that are "in phase" with each other to the first and second adjacent electrodes 30 and 31. Corresponding power modules (e.g., first power module and second power module 2021, 2022) supply the same sinusoidal electrical signals Va and Vb to a given first or second electrode 30 and 31. In this way, generator 2 causes electrodes 30 and 31 to deliver a unipolar voltage to tissue 1 for irreversible electroporation, the resulting power being driven by the voltage difference between the first and second electrodes 30 and 31 and the ground potential (0V) associated with the return electrode 5. In this configuration, current flows from the first and second electrodes 30 and 31 to ground, i.e., to the return electrode 5, and there is no voltage difference between the first and second electrodes at any instant—therefore, there is no bipolar current between these electrodes.

[0104] As the voltage oscillates between positive and negative peak values, the current moves back and forth between the ablation site and return electrode 5. Figure 7 An example of the resulting electric field formed between electrode 3 and return electrode 5 is shown. Relatively deep ablation can be achieved using such a unipolar voltage, for example, up to approximately 20 mm in depth.

[0105] refer to Figure 8 In the absence of an electrical return path (i.e., the return electrode 5 and / or the associated return line 6 are disconnected), the power unit 201 is also configured to supply separate electrical signals S to adjacent electrodes 3, which are 180° out of phase with each other so that the electrodes 3 can provide bipolar voltages.

[0106] More specifically, generator 2 is configured to supply a first sinusoidal electrical signal Va to the first electrode 30 and a second sinusoidal electrical signal Vb to the second adjacent electrode 31. The second sinusoidal electrical signal Vb is "out of phase" with the first sinusoidal electrical signal Va, and more specifically, it still has a 180° phase difference compared to the first sinusoidal electrical signal Va. Corresponding power modules supply the first and second sinusoidal electrical signals Va and Vb; for example, first power module 2021 supplies the first sinusoidal electrical signal Va to the first electrode 30, and second power module 2022 supplies the second sinusoidal electrical signal Vb to the second electrode 31.

[0107] In this case, a voltage is applied only between each of the first electrode 30 and the second electrode 31, and as follows: Figure 9 As illustrated in the examples, the resulting electric field is relatively shallow and localized, for example, within the heart wall or blood pool. This shallow and localized electric field also helps to minimize muscle stimulation. Therefore, in this way, even using bipolar voltages, local ablation to a depth of at least 5 mm and possibly up to 8 mm is possible.

[0108] In addition to the foregoing, see also: Figure 10 In the presence of an electrical return path (i.e., the return electrode 5 and / or the associated return line 6 are connected), the power unit 201 is also configured to supply separate electrical signals S to adjacent electrodes 3, which are out of phase with each other so that the electrodes 3 provide a combination of bipolar voltage and unipolar voltage.

[0109] More specifically, the first electrode 30 of a pair of adjacent electrodes 3 is provided with a first sinusoidal electrical signal Va, and the second electrode 31 of the pair of adjacent electrodes 3 is provided with a second sinusoidal electrical signal Vb. Electrical return occurs primarily between the adjacent electrodes 30, 31, resulting in a bipolar voltage equal to Va - Vb between these adjacent electrodes 30, 31. However, the electrical return component does occur via the return electrode 5 and the associated return line 6, resulting in a first unipolar voltage equal to Va between each first electrode 30 and the return electrode 5, and a second unipolar voltage equal to Vb between each second electrode 31 and the return electrode 5.

[0110] The resulting electric field is Figure 11 As illustrated by example, the electric field allows for relatively deep irreversible ablation, such as ablation achieved using only a unipolar voltage, but with less muscle stimulation compared to muscle stimulation produced using only a unipolar voltage of the same magnitude.

[0111] Furthermore, the power unit 201 can change the degree to which the individual electrical signals S (i.e., the first sine wave signal and the second sine wave signals Va and Vb) supplied to adjacent electrodes 3 are out of phase with each other. More specifically, the power unit 201 (i.e., the individual power module 202 therein) can vary the degree to which the individual electrical signals S (i.e., the first sine wave signal and the second sine wave signals Va and Vb) supplied to adjacent electrodes 3 are out of phase with each other between 0° and 180°.

[0112] When the first and second sinusoidal electrical signals Va and Vb supplied to adjacent electrodes 3 are 0° out of phase with each other, that is, when the signals are actually in phase with each other, the electrodes only provide unipolar voltages Va and Vb of the same magnitude. Simultaneously, when the first and second sinusoidal electrical signals Va and Vb supplied to adjacent electrodes 3 are 180° out of phase with each other, the electrodes only provide a bipolar voltage of magnitude Va-Vb.

[0113] Conversely, when the first and second sinusoidal electrical signals Va and Vb supplied to adjacent electrodes 3 are out of phase with each other by a magnitude between 0° and 180°, the ratio of unipolar voltage to bipolar voltage depends on the phase difference. For example, when the phase difference is 60°, the magnitude of the bipolar voltage generated between two adjacent electrodes 30 and 31 is the same as the magnitude of the unipolar voltage generated between each electrode 30 and 31 and the return electrode 5. However, when the phase difference is 90°, the magnitude of the bipolar voltage generated between two adjacent electrodes 30 and 31 is 1.41 (i.e., √2) times the magnitude of the unipolar voltage generated between each electrode 30 and 31 and the return electrode 5. Thus, by changing the ratio of deeper penetrating unipolar voltage to smaller penetrating bipolar voltage, the depth of irreversible ablation can be modified. Furthermore, this combination of unipolar and bipolar voltages results in less muscle stimulation than when only the same unipolar voltage is applied. In other words, the presence of bipolar voltage also has a mitigating effect on reducing muscle stimulation.

[0114] In other embodiments of the invention (not shown), the generator (i.e., the power unit) can be configured, for example, to alternately supply unipolar and bipolar voltages to the electrodes via time-division multiplexing. In such an embodiment, the power unit may first supply unipolar voltages to the electrodes by applying a voltage between each electrode and the return electrode, and then, as a second step, supply bipolar voltages to the electrodes by applying a voltage between adjacent electrodes. Such first and second steps are preferably followed by a shutdown cycle.

[0115] According to other implementations of this kind, by selecting different combinations of unipolar and bipolar voltages, for example by multiplexing, the ratio of bipolar to unipolar voltages can be similarly changed, for example from 4:1 to all unipolar, thereby changing the achieved ablation depth again.

[0116] List of reference numerals

[0117] 100 electronic devices

[0118] 1. Biological tissues

[0119] 2 generators

[0120] 3 electrodes

[0121] 30 First Electrode

[0122] 31 Second Electrode

[0123] 4. Catheter

[0124] 5. Other electrodes, return electrodes

[0125] 6 Return Line

[0126] 7 lines

[0127] S electrical signal

[0128] S1 First Electrical Signal

[0129] S2 Second Electrical Signal

[0130] T1 First time interval

[0131] T2 Second time interval

[0132] SB basic sine wave

[0133] 200 individual control units

[0134] 201 Power Unit

[0135] 202 Power Module

[0136] 203 Driver Circuit Block - Amplifier Circuit with Emitter Follower Configuration

[0137] 204 Select Block - H-Bridge Circuit - Power Inverter Block

[0138] 205 First Series Resonant Filter

[0139] 206 Electrical Isolation Block - Transformer

[0140] 205′ Second Series Resonant Filter

[0141] 207 microprocessor

[0142] 208 Variable High-Voltage Power Supply Block

[0143] 209 Programmable Logic Controller Block

[0144] 210 Video Interface Block

[0145] 210′ Button Block

[0146] 211 Watchdog Block

[0147] 212 Audio Interface Block

[0148] 230 First Transformer Circuit

[0149] Vcc supply voltage signal - first DC power supply voltage

[0150] Vcc1 Supply Voltage Signal - Second DC Power Supply Voltage

[0151] PS1 First Pulse Signal

[0152] PS2 second pulse signal

[0153] Va, Vb sinusoidal electrical signals

[0154] 2021 First Power Module

[0155] 2022 Second Power Module

[0156] 2023 Third Power Module

[0157] 2024 Fourth Power Module

[0158] 2025 Fifth Power Module

[0159] 2026 Sixth Power Module

Claims

1. An electronic device (100) for delivering coherent sinusoidal pulse group irreversible electroporation energy to a biological tissue (1) to be treated, said electronic device comprising: At least one electrode (3) may be positioned on or near the biological tissue (1) to be treated; as well as A generator (2) for supplying electrical energy to the at least one electrode (3), the generator (2) being configured to generate a corresponding electrical signal (S) to excite the at least one electrode (3). in The corresponding electrical signal (S) is formed by alternating between a first electrical signal (S1) and a second electrical signal (S2) over time, and each first electrical signal (S1) is the same; The first electrical signal (S1) is supplied to the individual electrode (3) during a first time interval (T1) and the second electrical signal (S2) is supplied to the individual electrode (3) during a second time interval (T2) after 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 has a peak-to-peak average amplitude in the range of 2,000 V to 20,000 V and consists of a positive half-wave and a negative half-wave, each half-wave having the same width. The first electrical signal (S1) has a frequency in the range of 25 kHz to 75 kHz. The second electrical signal (S2) has an amplitude equal to zero in the second time interval (T2), the electronic device (100) includes a plurality of electrodes (3), wherein the generator (2) includes a single control unit (200) and a power unit (201) for generating the corresponding electrical signal (S); The power unit (201) is electrically connected to all of the electrodes (3) of the plurality of electrodes, which thereby provide one of a unipolar voltage, a bipolar voltage, or a combination of a bipolar voltage and a unipolar voltage; In the presence of an electrical return path, the power unit (201) is configured to supply separate electrical signals (S) that are out of phase with each other to adjacent electrodes (3) so that the electrodes (3) provide a combination of bipolar voltage and unipolar voltage; wherein the power unit (201) is configured to change the degree to which the separate electrical signals (S) supplied to adjacent electrodes (3) are out of phase with each other.

2. The electronic device (100) according to claim 1, wherein the first electrical signal (S1) has a frequency in the range of 35 kHz to 65 kHz.

3. The electronic device (100) according to claim 2, wherein the first electrical signal (S1) has a frequency in the range of 40 kHz to 60 kHz.

4. The electronic device (100) according to claim 3, wherein the first electrical signal (S1) has a frequency in the range of 45 kHz to 55 kHz.

5. The electronic device (100) according to any of the preceding claims, wherein the first electrical signal (S1) comprises two to fifteen fundamental sine waves (SB) in the first time interval (T1).

6. The electronic device (100) according to claim 1, wherein the second time interval (T2) of the second electrical signal (S2) has a duration of greater than or equal to 1 millisecond and less than or equal to 1 second.

7. The electronic device (100) according to claim 1, wherein the power unit (201) is configured such that the degree to which the individual electrical signals (S) supplied to the adjacent electrodes (3) are out of phase with each other varies between 0° and 180°.

8. A method for controlling at least one electrode (3) in an electronic device (100) for delivering coherent sinusoidal pulse group irreversible electroporation energy to a biological tissue (1) to be treated, the electronic device comprising a plurality of electrodes (3) positionable on or near the biological tissue (1) to be treated, and a generator (2) for supplying electrical energy to the at least one electrode (3), the generator (2) being configured to generate a corresponding electrical signal (S) to excite the at least one electrode (3), wherein the generator (2) comprises a single control unit (200) and a power unit (201) for generating the corresponding electrical signal (S); the power unit (201) being electrically connected to all of the plurality of electrodes (3), the plurality of electrodes thereby providing one of a unipolar voltage, a bipolar voltage, or a combination of a bipolar voltage and a unipolar voltage; The method includes the following steps: The corresponding electrical signal (S) is formed by alternating the first electrical signal (S1) and the second electrical signal (S2) over time, and each first electrical signal (S1) is the same; The first electrical signal (S1) is supplied to the individual electrode (3) during the first time interval (T1) and the second electrical signal (S2) is supplied to the individual electrode (3) during the 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) in the first time interval (T1), each fundamental sine wave having a peak-to-peak average amplitude in the range of 2,000 V to 20,000 V and consisting of a positive half-wave and a negative half-wave, each half-wave having the same width, and the first electrical signal (S1) having a frequency in the range of 25 kHz to 75 kHz, and the second electrical signal (S2) having an amplitude equal to zero in a second time interval (T2) following the first time interval (T1), wherein the method further comprises: In the presence of an electrical return path, the power unit (201) supplies separate electrical signals (S) that are out of phase with each other to adjacent electrodes (3) so that the electrodes (3) provide a combination of bipolar voltage and unipolar voltage; wherein the power unit (201) is configured to change the degree to which the separate electrical signals (S) supplied to adjacent electrodes (3) are out of phase with each other.

9. The method according to claim 8, wherein the first electrical signal (S1) has a frequency in the range of 35 kHz to 65 kHz.

10. The method of claim 9, wherein the first electrical signal (S1) has a frequency in the range of 40 kHz to 60 kHz.

11. The method of claim 10, wherein the first electrical signal (S1) has a frequency in the range of 45 kHz to 55 kHz.

12. The method according to any one of claims 8 to 11, wherein the first electrical signal (S1) comprises two to fifteen fundamental sine waves (SB) in the first time interval (T1).

13. The method according to claim 8, wherein the second time interval (T2) of the second electrical signal (S2) has a duration of greater than or equal to 1 millisecond and less than or equal to 1 second.

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