Systems and methods for detecting malfunctions in electroporation therapy

Abstract

An example system, apparatus, method, and computer program product are disclosed for electroporating cells in tissue using a set of voltage pulses generated by a capacitor charging circuit based on a voltage power supply. The example method includes: continuously monitoring a set of characteristics of the voltage power supply and the set of voltage pulses; generating a first set of monitoring signals based on the set of characteristics; detecting a first fault condition based on the first set of monitoring signals; and generating a first crowbar trigger activation signal. The example computer method further includes: detecting a second fault condition based on a second set of monitoring signals, the second set of monitoring signals being generated based on the first set of monitoring signals; and generating a second crowbar trigger activation signal. Subsequently, the example computer method includes disconnecting the capacitor charging circuit from the electroporation electrode circuit based on either the first crowbar trigger activation signal or the second crowbar trigger activation signal.

Description

Technical Field

[0001] The exemplary embodiments disclosed herein generally relate to using a control system to improve the electroporation process and increase cell permeability, and more specifically, to the optimized application of a controlled electric field for delivering therapeutic portions into cells via electroporation therapy (EPT), also known as cell perforation therapy (CPT) and electrochemical therapy (ECT). Background Technology

[0002] In the 1970s, scientists discovered that electric fields could be used to create pores in cells without causing permanent damage. This discovery made it possible to insert macromolecules into the cytoplasm. Therefore, therapeutic components, such as pharmacological compounds, can now be incorporated into living cells through a process called electroporation. Genes or other molecules are injected into living cells and short pulses of a high electric field are applied. The cell membrane briefly becomes porous, and the gene or molecule enters the cell, where it can modify the cell's genome.

[0003] When treating certain types of cancer with chemotherapy, it is necessary to use sufficiently high doses of the drug to kill cancer cells without killing an unacceptably large number of normal cells. This can be achieved if the chemotherapy drug can be inserted directly into the cancer cells. Some anticancer drugs, such as bleomycin, are often unable to effectively penetrate the membranes of some cancer cells. However, electroporation makes it possible to insert bleomycin into the cells.

[0004] Treatment typically involves injecting anticancer drugs directly into the tumor and applying an electric field to the tumor between a pair of electrodes. The field strength must be precisely and appropriately adjusted so that electroporation of the tumor cells does not damage any normal or healthy cells, or at least minimizes such damage. This can usually be easily achieved in external tumors by applying electrodes to opposite sides of the tumor so that the electric field is between the electrodes. Once the field is uniform, the distance between the electrodes can then be measured, and a suitable voltage can then be applied to the electrodes according to the formula E = V / d (E = field strength in V / cm; V = voltage in volts; and d = distance in cm). When treating large or internal tumors, properly positioning the electrodes and measuring the distance between them is not easy.

[0005] Treating subjects with electroporation therapy offers a means of avoiding the harmful effects typically associated with the administration of anticancer or cytotoxic agents. This treatment allows these agents to be introduced to selectively damage or kill unwanted cells while avoiding surrounding healthy cells or tissue. However, one problem with using electroporation techniques is that diseased tissue, especially cancerous tissue, can be quite heterogeneous, requiring adjustments to the electroporation conditions.

[0006] The applicant has identified numerous defects and problems associated with conventional EPT technology and electroporation systems, as well as the associated safety features. Through the application of effort, ingenuity, and innovation, many of these identified problems have been addressed by developing solutions incorporated into the embodiments of this disclosure, many of which are described in detail herein. Summary of the Invention

[0007] This document discloses systems, apparatus, methods, and computer program products for electroporating cells in tissue using a set of continuously monitored voltage pulses generated by a continuously monitored voltage power supply. Although the disclosure herein covers any voltage range, exemplary embodiments will be described with reference to high voltage (HV) and low voltage (LV) ranges.

[0008] In one example embodiment, a system is provided for electroporating cells in tissue using a set of voltage pulses generated based on a voltage power supply. The system may include a voltage generating circuit electrically connected to a capacitor charging circuit and a monitoring circuit. The voltage generating circuit may be configured to generate the voltage power supply and transmit the voltage power supply to the capacitor charging circuit. The system may further include the capacitor charging circuit. The capacitor charging circuit may be electrically connected to the voltage generating circuit, a crowbar trigger circuit, the monitoring circuit, and an electroporation electrode (EPE) circuit. The capacitor charging circuit may be configured to receive the voltage power supply from the voltage generating circuit, generate the set of voltage pulses based on the voltage power supply, and transmit the set of voltage pulses to the electroporation electrode circuit. The system may further include the monitoring circuit. The monitoring circuit may be electrically connected to the voltage generating circuit, the capacitor charging circuit, a monitoring and analysis circuit, and the crowbar trigger circuit. The monitoring circuit may be configured to continuously monitor a set of characteristics of the voltage power supply and the set of voltage pulses, generate a first set of monitoring signals based on the set of characteristics, and transmit the first set of monitoring signals. The monitoring circuit may be further configured to: detect a first fault condition based on the first set of monitoring signals; generate a first crowbar trigger activation signal in response to detecting the first fault condition; and transmit the first crowbar trigger activation signal to the crowbar trigger circuit. The system may further include the monitoring and analysis circuit. The monitoring and analysis circuit may be electrically connected to the crowbar trigger circuit. The monitoring and analysis circuit may be configured to: receive a second set of monitoring signals generated based on the first set of monitoring signals; detect a second fault condition based on the second set of monitoring signals; generate a second crowbar trigger activation signal in response to detecting the second fault condition; and transmit the second crowbar trigger activation signal to the crowbar trigger circuit. The system may further include the crowbar trigger circuit. The crowbar trigger circuit may be electrically connected to the monitoring circuit and the monitoring and analysis circuit. The crowbar trigger circuit may be configured to: receive the first crowbar trigger activation signal from the monitoring circuit; receive the second crowbar trigger activation signal from the monitoring and analysis circuit; and disconnect the capacitor charging circuit from the electroporation electrode circuit in response to receiving either the first or second crowbar trigger activation signal.

[0009] In another embodiment, an apparatus is provided for electroporating cells in tissue using a set of voltage pulses generated based on a voltage power supply. The apparatus may include a voltage generating circuit electrically connected to a capacitor charging circuit and a monitoring circuit. The voltage generating circuit may be configured to generate the voltage power supply and transmit the voltage power supply to the capacitor charging circuit. The apparatus may further include the capacitor charging circuit. The capacitor charging circuit may be electrically connected to the voltage generating circuit, a crowbar trigger circuit, the monitoring circuit, and an electroporation electrode circuit. The capacitor charging circuit may be configured to receive the voltage power supply from the voltage generating circuit, generate the set of voltage pulses based on the voltage power supply, and transmit the set of voltage pulses to the electroporation electrode circuit. The apparatus may further include the monitoring circuit. The monitoring circuit may be electrically connected to the voltage generating circuit, the capacitor charging circuit, a monitoring and analysis circuit, and the crowbar trigger circuit. The monitoring circuit may be configured to continuously monitor a set of characteristics of the voltage power supply and the set of voltage pulses, generate a first set of monitoring signals based on the set of characteristics, and transmit the first set of monitoring signals. The monitoring circuit may be further configured to: detect a first fault condition based on the first set of monitoring signals; generate a first crowbar trigger activation signal in response to detecting the first fault condition; and transmit the first crowbar trigger activation signal to the crowbar trigger circuit. The device may further include the monitoring and analysis circuit. The monitoring and analysis circuit may be electrically connected to the crowbar trigger circuit. The monitoring and analysis circuit may be configured to: receive a second set of monitoring signals generated based on the first set of monitoring signals; detect a second fault condition based on the second set of monitoring signals; generate a second crowbar trigger activation signal in response to detecting the second fault condition; and transmit the second crowbar trigger activation signal to the crowbar trigger circuit. The device may further include the crowbar trigger circuit. The crowbar trigger circuit may be electrically connected to the monitoring circuit and the monitoring and analysis circuit. The crowbar trigger circuit may be configured to: receive the first crowbar trigger activation signal from the monitoring circuit; receive the second crowbar trigger activation signal from the monitoring and analysis circuit; and disconnect the capacitor charging circuit from the electroporation electrode circuit in response to receiving either the first or second crowbar trigger activation signal.

[0010] In another embodiment, an apparatus is provided for electroporating cells in tissue using a set of voltage pulses generated by a voltage power supply. The apparatus may include a monitoring circuit electrically connected to a crowbar trigger circuit. The monitoring circuit may be configured to continuously monitor a set of characteristics of the voltage power supply and the set of voltage pulses. The monitoring circuit may also be configured to generate a first set of monitoring signals based on the set of characteristics. The monitoring circuit may be further configured to transmit the first set of monitoring signals. The monitoring circuit may be further configured to detect a first fault condition based on the first set of monitoring signals. The monitoring circuit may be further configured to generate a first crowbar trigger activation signal in response to detecting the first fault condition. The monitoring circuit may be further configured to transmit the first crowbar trigger activation signal to the crowbar trigger circuit. The apparatus may further include a monitoring analysis circuit electrically connected to the crowbar trigger circuit. The monitoring analysis circuit may be configured to receive a second set of monitoring signals generated based on the first set of monitoring signals. The monitoring analysis circuit may be further configured to detect a second fault condition based on the second set of monitoring signals. The monitoring analysis circuit may be further configured to generate a second crowbar trigger activation signal in response to detecting the second fault condition. The monitoring and analysis circuit may be further configured to transmit the second crowbar trigger activation signal to the crowbar trigger circuit. The device may further include the crowbar trigger circuit. The crowbar trigger circuit may be electrically connected to the monitoring circuit and the monitoring and analysis circuit. The crowbar trigger circuit may be configured to receive the first crowbar trigger activation signal from the monitoring circuit. The crowbar trigger circuit may be further configured to receive the second crowbar trigger activation signal from the monitoring and analysis circuit. The crowbar trigger circuit may be further configured to disconnect the voltage power supply from the electroporation electrode circuit in response to receiving either the first or second crowbar trigger activation signal.

[0011] In another embodiment, a method is provided for electroporating cells in tissue using a set of voltage pulses generated by a voltage power supply. The method may include: generating the voltage power supply by a voltage generating circuit; and transmitting the voltage power supply to a capacitor charging circuit by the voltage generating circuit. The method may further include: receiving the voltage power supply from the voltage generating circuit by the capacitor charging circuit; generating the set of voltage pulses by the capacitor charging circuit based on the voltage power supply; and transmitting the set of voltage pulses to an electroporation electrode circuit by the capacitor charging circuit. The method may further include: continuously monitoring a set of characteristics of the voltage power supply and the set of voltage pulses by a monitoring circuit; generating a first set of monitoring signals by the monitoring circuit based on the set of characteristics; transmitting the first set of monitoring signals by the monitoring circuit; detecting a first fault condition by the monitoring circuit based on the first set of monitoring signals; generating a first crowbar trigger activation signal by the monitoring circuit in response to detecting the first fault condition; and transmitting the first crowbar trigger activation signal to a crowbar trigger circuit by the monitoring circuit. The method may further include: receiving a second set of monitoring signals generated based on the first set of monitoring signals by a monitoring and analysis circuit; detecting a second fault condition by the monitoring and analysis circuit based on the second set of monitoring signals; generating a second crowbar trigger activation signal by the monitoring and analysis circuit in response to detecting the second fault condition; and transmitting the second crowbar trigger activation signal to the crowbar trigger circuit by the monitoring and analysis circuit. The method may further include: receiving either the first crowbar trigger activation signal or the second crowbar trigger activation signal by the crowbar trigger circuit; and disconnecting the capacitor charging circuit from the electroporation electrode circuit in response to receiving either the first or the second crowbar trigger activation signal.

[0012] In yet another embodiment, a computer program product is provided for electroporating cells in tissue using a set of voltage pulses generated based on a voltage power supply. The computer program product may include at least one non-transitory computer-readable storage medium storing computer-executable program code instructions, which, when executed by a computing system, cause the computing system to: generate the voltage power supply by a voltage generation circuit; and transmit the voltage power supply to a capacitor charging circuit by the voltage generation circuit. The computer-executable program code instructions, when executed by the computing system, may further cause the computing system to: receive the voltage power supply from the voltage generation circuit by the capacitor charging circuit; generate the set of voltage pulses based on the voltage power supply by the capacitor charging circuit; and transmit the set of voltage pulses to an electroporation electrode circuit by the capacitor charging circuit. The computer-executable program code instructions, when executed by the computing system, may further cause the computing system to receive a second set of monitoring signals generated based on a first set of monitoring signals by a monitoring and analysis circuit. The first set of monitoring signals may have already been generated by the monitoring circuit based on a set of characteristics of the voltage power supply and the set of voltage pulses under continuous monitoring. When executed by the computing system, the computer-executable program code instructions can further cause the computing system to: detect a fault condition based on the second set of monitoring signals by the monitoring and analysis circuit; generate a crowbar trigger activation signal by the monitoring and analysis circuit in response to detecting the fault condition; and transmit the crowbar trigger activation signal to the crowbar trigger circuit by the monitoring and analysis circuit. When executed by the computing system, the computer-executable program code instructions can further cause the computing system to: receive the first crowbar trigger activation signal or the second crowbar trigger activation signal by the crowbar trigger circuit; and disconnect the capacitor charging circuit from the electroporation electrode circuit in response to receiving the first crowbar trigger activation signal or the second crowbar trigger activation signal.

[0013] The above-described invention is merely intended to summarize some exemplary embodiments to provide a basic understanding of some aspects of this disclosure. Therefore, it should be understood that the above embodiments are merely examples and should not be construed as limiting the scope or spirit of this disclosure in any way. It should be understood that the scope of this disclosure covers many possible embodiments in addition to those outlined herein, some of which will be further described below. Attached Figure Description

[0014] Having already described some exemplary embodiments of this disclosure in general terms above, reference will now be made to the accompanying drawings, which illustrate exemplary embodiments and features of this disclosure and are not necessarily drawn to scale. It should be understood that the components and structures shown in the drawings may or may not be present in the various embodiments of this disclosure described herein. Therefore, some embodiments or features of this disclosure may include fewer or more components or structures than those shown in the drawings without departing from the scope of this disclosure.

[0015] Figure 1 Example EPT treatment instruments are shown according to some exemplary embodiments described herein.

[0016] Figure 2 Schematic block diagrams illustrating some of the exemplary embodiments described herein are shown.

[0017] Figure 3A , Figure 3B , Figure 3C and Figure 3D An example block diagram of an EPT treatment device according to some exemplary embodiments described herein is shown.

[0018] Figure 4A , Figure 4B and Figure 4C Example circuit block diagrams are shown according to some exemplary embodiments described herein.

[0019] Figure 5A , Figure 5B , Figure 5C , Figure 5D , Figure 5E , Figure 5F , Figure 5G , Figure 5H , Figure 5I and Figure 5J Examples of schematic diagrams are shown based on some of the exemplary embodiments described herein.

[0020] Figure 6A , Figure 6B and Figure 6C Example pulse voltage signals are shown according to some exemplary embodiments described herein.

[0021] Figure 7 A flowchart illustrating an example method according to some example embodiments described herein. Detailed Implementation

[0022] The following description should be read with reference to the accompanying drawings, wherein the same reference numerals indicate the same elements throughout several views. The detailed description and drawings illustrate several embodiments intended to explain this disclosure. It should be understood that any designations of the disclosed features (e.g., first, second, etc.) and / or directional terms used in conjunction with the disclosed features (e.g., front, back, lower, upper, etc.) are relative terms indicating a schematic relationship between related features.

[0023] First, it should be understood that although illustrative embodiments of one or more aspects are shown below, the disclosed components, systems, and methods can be implemented using any number of techniques, whether currently known or not yet available. This disclosure should in no way be limited to the illustrative embodiments, figures, and techniques shown below, but can be modified within the scope of the appended claims and all their equivalents. Although values ​​for the dimensions of various elements are disclosed, the figures may not be drawn to scale.

[0024] When used herein, the term “example” is intended to mean “serving as an example, illustration, or explanation.” Any implementation described herein as an “example” is not necessarily preferred or superior to other implementations.

[0025] The exemplary embodiments described herein provide systems, apparatus, methods, and computer program products for EPT treatment instruments that provide electroporation of cells in tissue using a set of pulses (e.g., HV pulses, LV pulses) generated by a voltage-based power supply (e.g., HV power supply, LV source). In some cases, the EPT treatment instrument may provide redundant safety protocols, including hardware-based safety protocols (e.g., monitoring circuit 240) and software-based safety protocols (e.g., executed by monitoring and analysis circuit 270). For example, the EPT treatment instrument disclosed herein provides the use of four hardware monitoring circuits in addition to four software monitoring circuits to detect fault conditions, each configured to activate the crowbar trigger circuit described herein in the event of a fault condition (e.g., overvoltage, overcurrent). Furthermore, if the crowbar trigger circuit fails, the relay circuit described herein includes two relays configured to cut off power and prevent overvoltage or overcurrent dissipation to the patient.

[0026] In some embodiments, the EPT treatment device disclosed herein provides: continuous monitoring of a set of characteristics and a set of voltage pulses of a voltage power supply; generation of a set of analog monitoring signals based on the set of characteristics; detection of a first fault condition (e.g., overvoltage, overcurrent) based on the set of analog monitoring signals; detection of a second fault condition based on a set of digital monitoring signals; and, in response to the detection of the first or second fault condition, disconnection of the voltage pulses and voltage power supply from the electroporation electrode needle via a crowbar trigger circuit to prevent overvoltage and overcurrent from being applied to the patient.

[0027] In some embodiments, the EPT treatment device disclosed herein provides the use of a lower voltage (e.g., 5 volts instead of 50 volts) during needle placement verification to provide improved patient safety while verifying proper placement of the EPE needle electrode. For example, the EPT treatment device can be used in conjunction with a low-voltage electroporation assembly to provide detection of appropriate tissue resistance and applicator resistance. In some embodiments, the voltage for low-voltage applications is about 5 Vdc, and in some embodiments, the voltage for high-voltage applications is between about 400 Vdc and about 1300 Vdc.

[0028] The embodiments disclosed herein have many advantages, such as: improved detection of fault conditions through multiple redundant analog and digital circuits; prevention of any overvoltage or overcurrent applied to the patient through a crowbar trigger circuit; improved patient safety by using a lower voltage pulse during needle placement verification; and improved charging speed of the capacitor charging circuit because an impedance monitoring circuit, rather than a capacitor charging circuit, is used for needle placement verification.

[0029] Figure 1 This is a diagram of an EPT (Electroporation Therapy) instrument 100 that uses a set of pulses (e.g., HV pulses, LV pulses) generated by a voltage-based power supply to electroporate cells in tissue. An electroporation electrode applicator 112 can be removably coupled to the EPT instrument 100, which can be configured to selectively apply voltage pulses to selected electroporation electrode needles 114 of the electroporation electrode applicator 112. The pulse duration, voltage level, and electroporation electrode needle addressing or switching mode output by the EPT instrument 100 are all programmable.

[0030] Display 116 indicates the treatment voltage setpoint. A remote treatment activation connection 118 is provided to accommodate a foot switch 120 for activating pulses of the electroporation electrode applicator 112. The foot switch 120 allows the physician to activate the EPT treatment instrument 100 while freeing their hands to position the electroporation electrode applicator 112 in the patient's tissue. For convenience, status indicator lights 122 are provided for power-on (122A), fault detection (122B), and completion of treatment phase (122C). An electroporation electrode indicator light 124 is provided to clearly indicate that the electroporation electrode applicator 112 is connected to the EPT treatment instrument 100 and to indicate the type of electroporation electrode needle array (e.g., 4, 6, 9, or 16 electroporation electrode needles). A standby / reset button 126 is provided to "pause" the instrument and reset all functions of the EPT treatment instrument 100 to their default states. A ready button 128 is provided to prepare the EPT treatment instrument 100 for treatment phases. A prominent “Treatment in Progress” indicator light 130 indicates that a voltage pulse is being applied to the electroporation electrode needle 114. Additionally, the EPT treatment instrument 100 may have an audio indicator for functions such as button presses, fault status, start or end of treatment phases, indication of treatment in progress, and other suitable functions.

[0031] In some embodiments, the EPT treatment device 100 can provide electroporation of cells in tissue using a set of voltage pulses generated based on a voltage power supply. The EPT treatment device 100 can provide: generating a voltage power supply, generating a set of voltage pulses based on the voltage power supply, and transmitting the set of voltage pulses to the electroporation electrode needle 114. The EPT treatment device 100 can further provide: continuously monitoring a set of characteristics of the voltage power supply and a set of voltage pulses; generating a set of analog monitoring signals based on the set of characteristics; detecting a first fault condition (e.g., overvoltage, overcurrent) based on the set of analog monitoring signals; detecting a second fault condition (e.g., overvoltage, overcurrent) based on a set of digital monitoring signals (e.g., a digital version of the set of analog monitoring signals); and, in response to detecting the first or second fault condition, disconnecting the voltage pulses and voltage power supply from the electroporation electrode needle 114 via a crowbar trigger circuit disposed in the EPT treatment device 100 to prevent the application of overvoltage and overcurrent to the patient.

[0032] In some embodiments, the EPT therapy device 100 may be coupled to a feedback sensor configured to detect the patient's heartbeat. By synchronizing the application of voltage pulses near the heart to a safe cycle between heartbeats, the likelihood of the applied voltage pulses interfering with the normal heart rhythm can be reduced. Additional disclosures relating to the EPT therapy device and its advantages are made in U.S. Patent No. 7,412,284, published August 12, 2008, and U.S. Patent Application No. 15 / 563,462, filed September 29, 2017, both of which are incorporated herein by reference.

[0033] refer to Figure 1 The described EPT treatment device 100 can be made of, for example... Figure 2 One or more devices, such as device 200, are implemented. Device 200 can be configured to perform the above-described... Figure 1 The described operation, and the following text about Figure 3A , Figure 3B , Figure 3C , Figure 3D , Figure 4A , Figure 4B , Figure 4C , Figure 5A , Figure 5B , Figure 5C , Figure 5D , Figure 5E , Figure 5F , Figure 5G , Figure 5H , Figure 5I , Figure 5J , Figure 6A , Figure 6B , Figure 6C and Figure 7 The described operations. Although some of these components 210-296 are described in terms of their functional capabilities, it should be understood that a particular implementation necessarily involves the use of specific hardware to implement such functional capabilities. It should also be understood that some of these components 210-296 may contain similar or common hardware. For example, both sets of circuits can utilize the same electrical connections, ADCs, network interfaces, processors, memory, etc., to perform their associated functions, so that each set of circuits does not require duplicate hardware.

[0034] The term "circuit" as used herein with respect to components of device 200 therefore includes specific hardware configured to perform functions associated with the corresponding circuits described herein. Of course, while the term "circuit" should be interpreted broadly to include hardware, in some embodiments, a circuit may also include program code instructions for configuring the hardware. For example, in some embodiments, a "circuit" may include processing circuitry (e.g., digital signal processing (DSP) components), storage media, network interfaces, input / output devices, and other components. In some embodiments, other elements of device 200 may provide or supplement the functionality of a particular circuit. For example, processor 262 may provide processing functionality, memory 264 may provide storage functionality, communication circuitry 268 may provide network interface functionality, and so on.

[0035] like Figure 2 As shown, device 200 may include an HV circuit 210, an electroporation electrode (EPE) circuit 220, a crowbar trigger circuit 230, a monitoring circuit 240 (e.g., a hardware-based monitoring circuit), a processing circuit 260, a control circuit 290, and an analog-to-digital converter (ADC) circuit 296. HV circuit 210 may include an HV generation circuit 212, a gate drive circuit 214, and a capacitor charging circuit 216. EPE circuit 220 may include an HV relay circuit 222 (e.g., including a set of relays) and an EPE pin circuit 224. Monitoring circuit 240 may include an impedance monitoring circuit 242, a current monitoring circuit 244, a pulse monitoring circuit 246, a capacitance monitoring circuit 248, an HV monitoring circuit 250, and an HV power supply monitoring circuit 252. Processing circuit 260 may include a processor 262, a memory 264, an input-output circuit 266, a communication circuit 268, a user interface circuit 269, and a monitoring and analysis circuit 270 (e.g., a software-based monitoring circuit). The monitoring and analysis circuit 270 may include an impedance monitoring and analysis circuit 272, a current monitoring and analysis circuit 274, a pulse monitoring and analysis circuit 276, a capacitance monitoring and analysis circuit 278, an HV monitoring and analysis circuit 280, and a crowbar trigger control signal generation circuit 282. The control circuit 290 may include a digital potentiometer circuit 292 and a digital potentiometer HV control circuit 294.

[0036] HV generation circuit 212 may be electrically connected to gate drive circuit 214, capacitor charging circuit 216, monitoring circuit 240, processing circuit 260, digital potentiometer HV control circuit 294, and ADC circuit 296. HV generation circuit 212 may be configured to generate a voltage power supply (e.g., HV power supply, LV source) and transmit the voltage power supply to capacitor charging circuit 216. Capacitor charging circuit 216 may be electrically connected to HV generation circuit 212, crowbar trigger circuit 230, monitoring circuit 240, and EPE circuit 220. Capacitor charging circuit 216 may be configured to receive the voltage power supply from HV generation circuit 212, generate a set of voltage pulses (e.g., HV pulses, LV pulses) based on the voltage power supply, and transmit the set of voltage pulses to electroporation electrode circuit 220 (e.g., via HV relay circuit 222). In some embodiments, a set of voltage pulses may comprise approximately 6 to approximately 10 pulses per group. In some embodiments, the duration (e.g., pulse width) of each voltage pulse in the set of voltage pulses can be between about 70 microseconds and about 150 microseconds. In some embodiments, the duration (e.g., pulse width) of each voltage pulse in the set of voltage pulses can be between about 100 microseconds and about 1 millisecond. For example, the duration of each voltage pulse in the set of voltage pulses can be about 100 microseconds. In some embodiments, the term "voltage" refers to direct current (DC) voltage, and the term "volt" refers to Vdc. In some embodiments, the HV generating circuit 212 may be referred to as a "voltage generating circuit" and may include an HV generating circuit configured to generate an HV power supply, an LV generating circuit configured to generate an LV source, or both. In other embodiments, the LV generating circuit may be constituted by device 200 in addition to the HV generating circuit. In some embodiments, using a field strength of 700 V / cm or greater, the voltage of the HV power supply can be between about 600 volts and 3,000 volts. In some embodiments, the voltage of the HV power supply can be between about 1,000 volts and 1,750 volts, and the amperage of the HV power supply can be between about 40 amperes and 60 amperes. For example, the voltage of the HV power supply can be about 1,500 volts, and the amperage of the HV power supply can be about 70 amperes. In some embodiments, the voltage of the HV power supply can be between about 400 volts and 1,300 volts. In some embodiments, the voltage of the LV source generated by the HV generating circuit 212 or by a separate LV generating circuit constituted by device 200 can be about 5 volts.

[0037] Monitoring circuit 240 can be electrically connected to HV generation circuit 212, capacitor charging circuit 216, monitoring and analysis circuit 270, and crowbar trigger circuit 230. Monitoring circuit 240 can be configured to continuously monitor a set of characteristics and a set of voltage pulses of the voltage power supply, generate a first set of monitoring signals based on the set of characteristics, and transmit the first set of monitoring signals to digital potentiometer circuit 292 and ADC circuit 296. The first set of monitoring signals can include a set of analog monitoring signals, such as analog continuously monitored HV voltage signals (HV_MON), analog continuously monitored capacitor voltage signals (CAP_MON, VAR_CAP_V), analog continuously monitored pulse voltage signals (PULSE_MON, VAR_PULSE_V), analog continuously monitored current signals (CURRENT_MON), analog continuously monitored impedance voltage signals (IMPEDANCE_MON), analog continuously monitored HV power supply voltage signals (BV_MON), analog continuously monitored HV power supply current signals (BC_MON), any other suitable analog monitoring signals, or any combination thereof.

[0038] The monitoring circuit 240 may be further configured to: detect a first fault condition based on a first set of monitoring signals; generate a first crowbar trigger activation signal in response to the detection of the first fault condition; and transmit the first crowbar trigger activation signal to the crowbar trigger circuit 230. The first fault condition may include simulated fault conditions, such as simulated HV overvoltage conditions, simulated capacitor overvoltage conditions, simulated pulse overvoltage signal conditions, simulated overcurrent signal conditions, any other suitable simulated fault conditions, or any combination thereof. The first crowbar trigger activation signal may include simulated crowbar trigger activation signals, such as HV overvoltage signals (nHV_OV), capacitor overvoltage signals (nCAP_OV), pulse overvoltage signals (nPULSE_OV), overcurrent signals (nOVER_CURRENT), any other suitable simulated crowbar trigger activation signals, or any combination thereof.

[0039] In some embodiments, monitoring circuit 240 may include HV monitoring circuit 250. HV monitoring circuit 250 may be configured to: continuously monitor the HV voltage (+HV) of the HV power supply, wherein the set of characteristics includes the continuously monitored HV voltage; generate a first continuously monitored HV voltage signal (HV_MON) based on the continuously monitored HV voltage, wherein the first set of monitoring signals includes the first continuously monitored HV voltage signal; detect a first HV overvoltage condition (e.g., an analog HV voltage greater than or equal to 1,512 volts, and the HV power supply voltage is 1,500 volts) based on the first continuously monitored HV voltage signal, wherein the first fault condition is the first HV overvoltage condition; and generate a first HV overvoltage signal (nHV_OV) in response to detecting the first HV overvoltage condition, wherein a first crowbar trigger activation signal is the first HV overvoltage signal.

[0040] In some embodiments, monitoring circuit 240 may include capacitance monitoring circuit 248. Capacitance monitoring circuit 248 may be configured to: continuously monitor the capacitor voltage (CAP_V) of capacitor charging circuit 216, wherein the set of characteristics includes the continuously monitored capacitor voltage; generate a first continuously monitored capacitor voltage signal (CAP_MON) based on the continuously monitored capacitor voltage, wherein the first set of monitoring signals includes the first continuously monitored capacitor voltage signal; detect a first capacitor overvoltage condition (e.g., analog capacitor voltage exceeding analog capacitor voltage overvoltage (VAR_CAP_V)) based on the first continuously monitored capacitor voltage signal, wherein the first fault condition is the first capacitor overvoltage condition; and generate a first capacitor overvoltage signal (nCAP_OV) in response to detecting the first capacitor overvoltage condition, wherein the first crowbar trigger activation signal is the first capacitor overvoltage signal.

[0041] In some embodiments, the monitoring circuit 240 may include a pulse monitoring circuit 246. The pulse monitoring circuit 246 may be configured to: continuously monitor the pulse voltage (-HV_PULSE) of a set of HV pulses, wherein the set of characteristics includes the continuously monitored pulse voltage; generate a first continuously monitored pulse voltage signal (PULSE_MON) based on the continuously monitored pulse voltage, wherein the first set of monitoring signals includes the first continuously monitored pulse voltage signal; detect a first pulse overvoltage condition (e.g., an analog pulse voltage exceeding an analog pulse voltage overvoltage (VAR_PULSE_V)) based on the first continuously monitored pulse voltage signal, wherein the first fault condition is the first pulse overvoltage condition; and generate a first pulse overvoltage signal (nPULSE_OV) in response to detecting the first pulse overvoltage condition, wherein the first crowbar trigger activation signal is the first pulse overvoltage signal.

[0042] In some embodiments, monitoring circuit 240 may include current monitoring circuit 244. Current monitoring circuit 244 may be configured to: continuously monitor the current of a set of HV pulses, wherein the set of characteristics includes the continuously monitored current; generate a first continuously monitored current signal (CURRENT_MON) based on the continuously monitored current, wherein the first set of monitoring signals includes the first continuously monitored current signal; detect a first overcurrent condition (e.g., analog current exceeding an analog overcurrent value) based on the first continuously monitored current signal, wherein the first fault condition is the first overcurrent condition; and generate a first overcurrent signal (nOVER_CURRENT) in response to detecting the first overcurrent condition, wherein a first crowbar trigger activation signal is the first overcurrent signal.

[0043] In some embodiments, the monitoring circuit 240 may be electrically connected to a set of relays comprising an HV relay circuit 222. The monitoring circuit 240 may include an impedance monitoring circuit 242. The impedance monitoring circuit 242 may be configured to: generate a set of low-voltage (LV) pulses (e.g., 5 volts instead of 50 volts); transmit the set of LV pulses to the electroporation electrode circuit 220; receive a set of LV return pulses from the electroporation electrode circuit 220; monitor the resistance of the tissue based on the set of LV return pulses; and generate a first monitored impedance voltage signal (IMPEDANCE_MON) based on the monitored resistance. The impedance monitoring circuit 242 may be further configured to: detect a first impedance test fault condition (e.g., an analog resistance less than typical skin resistance (e.g., 20 ohms)) based on the first monitored impedance voltage signal; and generate a first set of relay deactivation signals in response to detecting the first impedance test fault condition; and transmit the first set of relay deactivation signals to the set of relays. Each of the relays in the group can be configured to: receive a relay deactivation signal from the impedance monitoring circuit 242; and in response to receiving a relay deactivation signal from the first group of relay deactivation signals, disconnect the capacitor charging circuit 216 from the EPE pin circuit 224.

[0044] The monitoring and analysis circuit 270 can be electrically connected to the crowbar trigger circuit 230 and the ADC circuit 296. The monitoring and analysis circuit 270 can be configured to: receive a second set of monitoring signals generated based on the first set of monitoring signals; detect a second fault condition based on the second set of monitoring signals; generate a second crowbar trigger activation signal in response to detecting the second fault condition; and transmit the second crowbar trigger activation signal to the crowbar trigger circuit.

[0045] The second set of monitoring signals may include a set of digital monitoring signals, such as digitally continuously monitored HV voltage signals (digital HV_MON), digitally continuously monitored capacitor voltage signals (digital CAP_MON, digital VAR_CAP_V), digitally continuously monitored pulse voltage signals (digital PULSE_MON, digital VAR_PULSE_V), digitally continuously monitored current signals (digital CURRENT_MON), digitally continuously monitored impedance voltage signals (digital IMPEDANCE_MON), digitally continuously monitored HV power supply voltage signals (digital BV_MON), digitally continuously monitored HV power supply current signals (digital BC_MON), any other suitable digital monitoring signals, or any combination thereof. In some embodiments, the monitoring analysis circuit 270 may be configured to receive the second set of monitoring signals from the ADC circuit 296. For example, the first set of monitoring signals may be a set of analog monitoring signals transmitted from the monitoring circuit 240 to the ADC circuit 296, and the second set of monitoring signals may be a set of digital monitoring signals generated by the ADC circuit 296 based on the set of analog monitoring signals and transmitted by the ADC circuit 296 to the monitoring analysis circuit 270.

[0046] The monitoring and analysis circuit 270 may be further configured to: detect a second fault condition based on the second set of monitoring signals; generate a second crowbar trigger activation signal in response to the detection of the second fault condition; and transmit the second crowbar trigger activation signal to the crowbar trigger circuit. The second crowbar trigger activation signal may include a digital crowbar trigger activation signal (nMICRO_CROWBAR), any other suitable crowbar trigger activation signal, or any combination thereof.

[0047] In some embodiments, the monitoring and analysis circuit 270 may be electrically connected to a group of relays comprising the HV relay circuit 222. The monitoring and analysis circuit 270 may be further configured to: generate a group of relay deactivation signals in response to the detection of a second fault condition; and transmit the group of relay deactivation signals to the group of relays. Each relay in the group of relays may be configured to: receive one relay deactivation signal from the monitoring and analysis circuit; and, in response to receiving one relay deactivation signal from the group of relay deactivation signals, disconnect the capacitor charging circuit 216 from the EPE pin circuit 224.

[0048] In some embodiments, the monitoring and analysis circuit 270 may include an HV monitoring and analysis circuit 280 and a crowbar trigger control signal generation circuit 282. The HV monitoring and analysis circuit 280 may be configured to: receive a second continuously monitored HV voltage signal (digital HV_MON) generated based on a first continuously monitored HV voltage signal, wherein the second set of monitoring signals includes the second continuously monitored HV voltage signal; detect a second HV overvoltage condition based on the second continuously monitored HV voltage signal (e.g., for a 1,500-volt HV power supply voltage, the digital HV voltage is higher than or equal to 1,512 volts), wherein the second fault condition is a second HV overvoltage condition; generate a second HV overvoltage signal in response to detecting the second HV overvoltage condition; and transmit the second HV overvoltage signal to the crowbar trigger control signal generation circuit 282. The crowbar trigger control signal generation circuit 282 can be configured to receive a second HV overvoltage signal from the HV monitoring and analysis circuit 280; in response to receiving the second HV overvoltage signal, generate a second crowbar trigger activation signal (nMICRO_CROWBAR); and transmit the second crowbar trigger activation control signal to the crowbar trigger circuit 230.

[0049] In some embodiments, the monitoring and analysis circuit 270 may include a capacitance monitoring and analysis circuit 278 and a crowbar trigger control signal generation circuit 282. The capacitance monitoring and analysis circuit 278 may be configured to: receive a second continuously monitored capacitor voltage signal (digital CAP_MON) generated based on a first continuously monitored capacitor voltage signal, wherein the second set of monitoring signals includes the second continuously monitored capacitor voltage signal; detect a second capacitor overvoltage condition (e.g., a digital capacitor voltage exceeding a digital capacitor voltage overvoltage (digital VAR_CAP_V)) based on the second continuously monitored capacitor voltage signal, wherein the second fault condition is a second capacitor overvoltage condition; generate a second capacitor overvoltage signal in response to detecting the second capacitor overvoltage condition; and transmit the second capacitor overvoltage signal to the crowbar trigger control signal generation circuit 282. The crowbar trigger control signal generation circuit 282 may be configured to: receive the second capacitor overvoltage signal from the capacitance monitoring and analysis circuit 278; generate a second crowbar trigger activation signal (nMICRO_CROWBAR) in response to receiving the second capacitor overvoltage signal; and transmit the second crowbar trigger activation control signal to the crowbar trigger circuit 230.

[0050] In some embodiments, the monitoring and analysis circuit 270 may include a pulse monitoring and analysis circuit 276 and a crowbar trigger control signal generation circuit 282. The pulse monitoring and analysis circuit 276 may be configured to: receive a second continuously monitored pulse voltage signal (digital PULSE_MON) generated based on a first continuously monitored pulse voltage signal, wherein the second set of monitoring signals includes the second continuously monitored pulse voltage signal; detect a second pulse overvoltage condition (e.g., a digital pulse voltage exceeding a digital pulse voltage overvoltage (digital VAR_PULSE_V)) based on the second continuously monitored pulse voltage signal, wherein the second fault condition is a second pulse overvoltage condition; generate a second pulse overvoltage signal in response to detecting the second pulse overvoltage condition; and transmit the second pulse overvoltage signal to the crowbar trigger control signal generation circuit 282. The crowbar trigger control signal generation circuit 282 may be configured to receive the second pulse overvoltage signal from the pulse monitoring and analysis circuit 276; generate a second crowbar trigger activation signal (nMICRO_CROWBAR) in response to receiving the second pulse overvoltage signal; and transmit a crowbar trigger activation control signal to the crowbar trigger circuit 230.

[0051] In some embodiments, the pulse monitoring and analysis circuit 276 may be further configured to: determine the rise time of the rising edge of a pulse in a set of pulses; and detect a second pulse overvoltage condition based on the rise time (e.g., the rise time exceeds a predetermined rise time threshold). In some embodiments, the pulse monitoring and analysis circuit 276 may be further configured to: determine the fall time of the falling edge of a pulse in the set of pulses; and detect a second pulse overvoltage condition based on the fall time (e.g., the fall time exceeds a predetermined fall time threshold).

[0052] In some embodiments, the monitoring and analysis circuit 270 may include a current monitoring and analysis circuit 274 and a crowbar trigger control signal generation circuit 282. The current monitoring and analysis circuit 274 may be configured to: receive a second continuously monitored current signal (digital CURRENT_MON) generated based on a first continuously monitored current signal, wherein the second set of monitoring signals includes the second continuously monitored current signal; detect a second overcurrent condition (e.g., digital current exceeding a digital current overcurrent value) based on the second continuously monitored current signal, wherein the second fault condition is a second overcurrent condition; generate a second overcurrent signal in response to detecting the second overcurrent condition; and transmit the second overcurrent signal to the crowbar trigger control signal generation circuit 282. The crowbar trigger control signal generation circuit 282 may be configured to receive a second pulse overcurrent signal from the current monitoring and analysis circuit 274; generate a second crowbar trigger activation signal (nMICRO_CROWBAR) in response to receiving the second pulse overcurrent signal; and transmit the second crowbar trigger activation control signal to the crowbar trigger circuit 230.

[0053] In some embodiments, the monitoring and analysis circuit 270 may be electrically connected to the set of relays constituted by the HV relay circuit 222. The monitoring and analysis circuit 270 may include an impedance monitoring and analysis circuit 272. The impedance monitoring and analysis circuit 272 may be configured to: receive a second monitored impedance voltage signal (digital IMPEDANCE_MON) generated based on the first monitored impedance voltage signal; detect a second impedance test fault condition (e.g., digital resistance less than 20 ohms) based on the second monitored impedance voltage signal; generate a second set of relay deactivation signals in response to detecting the second monitored impedance voltage signal; and transmit the second set of relay deactivation signals to the set of relays. Each relay in the set of relays may be configured to: receive a relay deactivation signal from the second set of relay deactivation signals from the impedance monitoring and analysis circuit; and disconnect the capacitor charging circuit 216 from the EPE pin circuit 224 in response to receiving a relay deactivation signal from the second set of relay deactivation signals.

[0054] The crowbar trigger circuit 230 can be electrically connected to the monitoring circuit 240 and the monitoring analysis circuit 270. The crowbar trigger circuit 230 can be configured to: receive a first crowbar trigger activation signal from the monitoring circuit 240; receive a second crowbar trigger activation signal from the monitoring analysis circuit 270; and, in response to receiving the first crowbar trigger activation signal or the second crowbar trigger activation signal, disconnect the HV circuit 210 from the electroporation electrode circuit 220, for example, by disconnecting the capacitor charging circuit 216 from the electroporation electrode circuit 220. In some embodiments, the crowbar trigger circuit 230 can be configured to disconnect the capacitor charging circuit 216 from the electroporation electrode circuit 220 within approximately 10 microseconds of detecting a first fault condition or detecting a second fault condition.

[0055] Processor 262 can be embodied in a variety of different ways and may, for example, include one or more processing devices configured to execute independently. Alternatively or concurrently, processor 262 may include one or more processors configured via a bus to enable independent execution of instructions, pipelining, multithreaded processing, or a combination thereof. The terms “processor” or “processing circuitry” can be understood to include a single-core processor, a multi-core processor, multiple processors within device 200, a remote or “cloud” processor, or a combination thereof.

[0056] In exemplary embodiments, processor 262 may be configured to execute instructions stored in memory 264 or otherwise accessible by processor 262. Alternatively or additionally, processor 262 may be configured to perform hard-coded functions. Thus, whether configured by hardware or software methods or by a combination of hardware and software, processor 262 may represent an entity (e.g., physically embodied in circuitry) capable of performing operations according to embodiments of this disclosure when appropriately configured. As another example, when processor 262 embodies an executor of program code instructions, the instructions may be specifically configured to perform the operations described herein when executing the instructions.

[0057] In some embodiments, processor 262 (and / or coprocessor or any other processing circuitry-assisted processor or otherwise associated with a processor) may communicate with memory 264 via a bus for transferring information between components of the device. Memory 264 may be non-transitory memory and may contain, for example, one or more volatile and / or non-volatile memories. For example, memory 264 may be an electronic storage device (e.g., a computer-readable storage medium). In another instance, memory 264 may be a non-transitory computer-readable storage medium storing computer-executable program code instructions that, when executed by a computing system, cause the computing system to perform the various operations described herein. Memory 264 may be configured to store information, data, content, signal applications, instructions (e.g., computer-executable program code instructions), etc., to enable device 200 to perform various functions according to exemplary embodiments of this disclosure. For example, memory 264 may be configured to store monitoring signals, fault conditions (e.g., overvoltage, overcurrent), detection techniques, crowbar trigger control signals (e.g., crowbar trigger activation signals), relay controls, control signals, or any combination thereof. It should be understood that memory 264 can be configured to store, in part or in whole, any electronic information, data, data structures, signals, embodiments, examples, diagrams, processes, operations, techniques, algorithms, instructions, systems, devices, methods, or computer program products described herein, or any combination thereof.

[0058] In some embodiments, processing circuitry 260 may include input-output circuitry 266, which can communicate with processor 262 to provide output to a user and, in some embodiments, can receive input such as commands provided by the user. Input-output circuitry 266 may include a user interface such as a graphical user interface (GUI) and may include a display that may contain a web user interface, GUI application, mobile application, client device, or any other suitable hardware or software. In some embodiments, input-output circuitry 266 may also include a keyboard, mouse, joystick, display device, display screen, touch screen, touch area, softkey, microphone, speaker, or other input-output mechanism. Processor 262, input-output circuitry 266 (which may utilize processor 262), or both may be configured to control one or more functions of one or more user interface elements via computer-executable program code instructions (e.g., software, firmware) stored in a non-transitory computer-readable storage medium (e.g., memory 264). Input-output circuitry 266 is optional, and in some embodiments, device 200 may not include input-output circuitry. For example, when device 200 does not directly interact with a user, device 200 can generate user interface data for display on one or more other devices, and one or more users can directly interact with those devices and transmit the generated user interface data to one or more of those devices. For example, device 200 can use user interface circuitry 269 to generate user interface data for display on one or more display devices and transmit the generated user interface data to those display devices.

[0059] Communication circuit 268 can be any device or circuit embodied in hardware or a combination of hardware and software, configured to receive data from or transmit data to a network or any other device, circuit, or module communicating with device 200. In this regard, communication circuit 268 may include, for example, a network interface for enabling communication with wired or wireless communication networks. For example, communication circuit 268 may include one or more network interface cards, antennas, buses, switches, routers, modems, and supporting hardware and / or software, or any other device suitable for enabling communication via a network. In some embodiments, the communication interface may include circuitry for interacting with an antenna to transmit signals through the antenna or for processing the reception of signals received via the antenna. These signals can be transmitted or received by device 200 using any of many Internet, Ethernet, cellular, satellite, or wireless technologies, such as IEEE 802.11, Code Division Multiple Access (CDMA), Global System for Mobile Communications (GSM), Universal Mobile Telecommunications System (UMTS), and Long Term Evolution (LTE). v1.0 to v5.0, Bluetooth Low Energy (BLE), Infrared Wireless (e.g., IrDA), Ultra Wideband (UWB), Inductive Wireless Transmission, Wi-Fi, Near Field Communication (NFC), Global Microwave Access Interoperability (WiMAX), Radio Frequency (RF), RFID, or any other suitable technology.

[0060] In some embodiments, the communication circuit 268 may include hardware components designed or configured to receive electronic indications from a user device of pulse duration (e.g., 100 microseconds), voltage level (e.g., 1,500 volts), and EPE pin addressing or switching mode output by device 200. In some embodiments, the communication circuit 268 may receive electronic indications in response to a user selecting a pulse duration, voltage level, or EPE pin addressing or switching mode from a list of pulse durations, voltage levels, or EPE pin addressing or switching modes displayed in a graphical user interface provided by user interface circuitry 269 using input-output circuitry 266.

[0061] User interface circuitry 269 includes hardware components designed or configured to receive, process, generate, and transmit data, such as user interface data. For example, user interface circuitry 269 includes components designed or configured to be based on a reference... Figure 1 , Figure 2 , Figure 3A , Figure 3B , Figure 3C , Figure 3D , Figure 4A , Figure 4B , Figure 4C , Figure 5A , Figure 5B , Figure 5C , Figure 5D , Figure 5E , Figure 5F , Figure 5G , Figure 5H , Figure 5I , Figure 5J , Figure 6A , Figure 6B , Figure 6C and Figure 7Hardware components used to generate user interface data in any of the embodiments or combinations thereof. In some embodiments, user interface circuitry 269 may communicate with a display device (e.g., input-output circuitry 266, display 116, user device, or a display device communicatively coupled thereto) and is therefore configured to transmit user interface data to the display device. For example, user interface circuitry 269 may be configured to generate user interface data and transmit the generated user interface data to input-output circuitry 266, and input-output circuitry 266 may be configured to receive user interface data and display the received user interface data on display 116. In some embodiments, user interface circuitry 269 may be configured to transmit user interface data to communication circuitry 268, and communication circuitry 268 may be configured to transmit user interface data to user device.

[0062] In some embodiments, each of the user interface circuitry 269, impedance monitoring and analysis circuitry 272, current monitoring and analysis circuitry 274, pulse monitoring and analysis circuitry 276, capacitance monitoring and analysis circuitry 278, HV monitoring and analysis circuitry 280, and crowbar trigger control signal generation circuitry 282 may include a separate processor, a specially configured field-programmable gate array (FPGA), a dedicated interface circuitry (ASIC), or a cloud utility to perform the functions described above. In some embodiments, the hardware components described above with reference to the user interface circuitry 269, impedance monitoring and analysis circuitry 272, current monitoring and analysis circuitry 274, pulse monitoring and analysis circuitry 276, capacitance monitoring and analysis circuitry 278, HV monitoring and analysis circuitry 280, and crowbar trigger control signal generation circuitry 282 may, for example, utilize communication circuitry 268 or any suitable wired or wireless communication path to communicate with the user device, with each other, or with any other suitable circuitry or device.

[0063] In some embodiments, one or more of the user interface circuitry 269, impedance monitoring and analysis circuitry 272, current monitoring and analysis circuitry 274, pulse monitoring and analysis circuitry 276, capacitance monitoring and analysis circuitry 278, HV monitoring and analysis circuitry 280, and crowbar trigger control signal generation circuitry 282 may be locally hosted by device 200. In some embodiments, one or more of the user interface circuitry 269, impedance monitoring and analysis circuitry 272, current monitoring and analysis circuitry 274, pulse monitoring and analysis circuitry 276, capacitance monitoring and analysis circuitry 278, HV monitoring and analysis circuitry 280, and crowbar trigger control signal generation circuitry 282 (e.g., hosted by one or more cloud servers) and therefore do not need to physically reside on device 200. Therefore, some or all of the functions described herein may be provided by remote circuitry. For example, device 200 may access one or more remote circuitries via any type of network connection that facilitates the transmission of data and electronic information between device 200 and the remote circuitry. Subsequently, device 200 can remotely communicate with one or more of the following: user interface circuit 269, impedance monitoring and analysis circuit 272, current monitoring and analysis circuit 274, pulse monitoring and analysis circuit 276, capacitance monitoring and analysis circuit 278, HV monitoring and analysis circuit 280, and crowbar trigger control signal generation circuit 282.

[0064] As described above based on this disclosure and as will be understood, embodiments of this disclosure can be configured as systems, devices, methods, mobile devices, back-end network devices, computer program products, other suitable devices, and combinations thereof. Therefore, embodiments can include various devices encompassing any combination of software and hardware. Furthermore, embodiments can take the form of a computer program product on at least one non-transitory computer-readable storage medium having computer-readable program instructions (e.g., computer software) embodied on the storage medium. Any suitable computer-readable storage medium can be utilized, including non-transitory hard disks, CD-ROMs, flash memory, optical storage devices, or magnetic storage devices. As will be understood, any computer program instructions and / or other types of code described herein can be loaded onto the circuitry of a computer, processor, or other programmable device to create a machine, such that the computer, processor, or other programmable circuitry executing the code on the machine forms means for implementing various functions, including those functions described herein.

[0065] A user device may be embodied in one or more computing devices or systems, which may further include processing circuitry, memory, input-output circuitry, and communication circuitry. For example, a user device may be a laptop computer on which an application (e.g., a GUI application) runs or is otherwise executed by the processing circuitry. In yet another example, a user device may be a smartphone on which an application (e.g., a web browsing application) runs or is otherwise executed by the processing circuitry. Due to the operations described in this disclosure, the functionality of these devices can utilize the features described above. Figure 2 The description refers to similar named components. For the sake of brevity, further mechanical descriptions of these components are omitted. These interconnected device elements provide the corresponding computing system with the functionality necessary to facilitate data communication with the EPT therapy instrument described herein.

[0066] After describing the specific components of the example apparatus involved in this disclosure, the following describes... Figure 3A , Figure 3B , Figure 3C , Figure 3D , Figure 4A , Figure 4B , Figure 4C , Figure 5A , Figure 5B , Figure 5C , Figure 5D , Figure 5E , Figure 5F , Figure 5G , Figure 5H , Figure 5I , Figure 5J , Figure 6A , Figure 6B , Figure 6C and Figure 7 A sample program for detecting fault conditions is described.

[0067] Figure 3A , Figure 3B , Figure 3C , Figure 3D Example block diagrams of EPT treatment devices according to some exemplary embodiments described herein are shown. Figure 3A As shown, block diagram 300 includes components that, in some cases, illustrate embodiments of the HV circuit 210, EPE circuit 220, crowbar trigger circuit 230, and monitoring circuit 240. Figure 3B As shown, block diagram 320 includes components that, in some cases, illustrate embodiments of processing circuitry 260, control circuitry 290, and ADC circuitry 296. Figure 3C As shown, block diagram 340 includes components that, in some cases, illustrate embodiments of additional processing circuitry and input-output circuitry. (As...) Figure 3DAs shown, block diagram 360 includes components that, in some cases, illustrate embodiments of additional power generation circuitry and input-output circuitry.

[0068] Figure 4A , Figure 4B , Figure 4C Example circuit block diagrams are shown according to some exemplary embodiments described herein. For example... Figure 4A As shown, circuit block diagram 400 includes HV relay circuit block 402 (e.g., showing signals received and transmitted by HV relay circuit 222), monitoring circuit block 404 (e.g., showing signals received and transmitted by monitoring circuit 240), processing circuit block 406 (e.g., showing signals received and transmitted by processing circuit 260), and connector circuit block 410 (e.g., showing signals received and transmitted by HV circuit 210, HV power monitoring circuit 252, and control circuit 290, etc.). Figure 4A As further shown, the processing circuit block 406 may include a monitoring and analysis circuit block 408 (e.g., signals received and transmitted by the monitoring and analysis circuit 270 are shown).

[0069] like Figure 4B As shown, circuit block diagram 420 includes multiple signal monitoring blocks (e.g., signals received and transmitted by ADC circuit 296 are shown).

[0070] In some embodiments, Figure 4B Each 0-ohm resistor shown can be placed as close as possible to the 30 position connector.

[0071] like Figure 4C As shown, circuit block diagram 440 includes a processing circuit block (e.g., signals received and transmitted by processing circuit 260 are shown). In some embodiments, component Y1 may be placed as close as possible to the processing circuit block. In some embodiments, processing circuit 260 may be implemented partially or entirely as Figure 4C The processing circuit block shown.

[0072] Figure 5A , Figure 5B , Figure 5C , Figure 5D , Figure 5E , Figure 5F , Figure 5G , Figure 5H , Figure 5I and Figure 5J Examples of schematic diagrams illustrating some of the exemplary embodiments described herein are shown. For example... Figure 5AAs shown, circuit 500 includes a gate drive circuit and a capacitor charging circuit. In some embodiments, the gate drive circuit 214 and the capacitor charging circuit 216 may be implemented partially or entirely as circuit 500. In some embodiments, the AGND and PGND terminals of component U15 are configured to be connected via a single coarse trace directly below component U15. In some embodiments, component Q1 is positioned to allow space for a heat sink, such as a clip on a heat sink. In some embodiments, the HV line is configured to carry a current of up to 90 amperes.

[0073] like Figure 5B As shown, circuit 510 includes a crowbar trigger circuit. In some embodiments, crowbar trigger circuit 230 may be implemented partly or entirely as circuit 510. In some embodiments, the crowbar trigger circuit may use an AND gate to receive signals from a microcontroller (e.g., processing circuitry 260) and analog components. In some embodiments, the high state of U21+U22 represents normal operation; the low state of U21+U22 transmits a crowbar activation signal.

[0074] In one illustrative example embodiment, the crowbar trigger circuit capacitor C49 is configured to be short-circuited via relay RE1, thereby causing converter T1, which crosses the capacitor charging circuit signals SCR_GATE and SCR_GATE_RTN, to generate a 5V signal, said converter being electrically coupled to... Figure 5A The circuit shown is 500. Figure 5A The generated 5V signal is applied to the gate of the silicon controlled rectifier (SCR) U17 in the circuit 500 shown, causing component U17 to enter a forward conduction mode, bypassing resistors R33, R34, R35, and R36. Therefore, the +HV line is pulled to zero, and all the charge on the HV capacitors C32, C33, and C34 flows through the series resistors R17, R29, and R31. Additionally, when -HV_PULSE changes from 0 to -1300Vdc, inductor L10 reverses the polarity and mitigates the subsequent current surge. Most of the current flows through the high-power resistors R17, R29, and R31, which are also adjusted to change the voltage decay rate.

[0075] In another illustrative example embodiment, circuit 510 is enabled when capacitor C49 is charged by the +5V_ISO rail. When a low active signal is sensed on one of the five inputs (nMICRO_CROWBAR, nCAP_OV, nHV_OV, nOVER_CURRENT, and nPULSE_OV), the gate of component Q2 goes low, thereby turning on the PMOS. Capacitor C49 discharges through component Q2, thereby sending a pulse to the gate of SCR U17 via transformer T1. Once the gate of the SCR receives the signal, it becomes forward biased, allowing any energy stored in HV capacitors C32, C33, and C34 to discharge. This energy is dissipated through resistors R17, R29, and R31, where inductor L10 limits current spikes. In the event that HV capacitors C32, C33, and C34 are charging and the system experiences a power failure, relay RE13 (e.g., relay RE13 coupled to...) Figure 5J The relay RE5 of EPE pin 1 shown is basically similar, but (coupled to EPE pin 6 instead of EPE pin 1) will close, thereby allowing capacitor C49 to discharge and activating circuit 510 as described above.

[0076] In some embodiments, by including hardware-based crowbar trigger inputs (e.g., nCAP_OV, nHV_OV, nOVER_CURRENT, nPULSE_OV) in addition to software-based crowbar trigger inputs (e.g., nMICRO_CROWBAR), circuit 510 can respond more quickly to any monitored condition (e.g., voltage, capacitance, current, pulse), where the circuit exceeds specifications compared to typical processor-based EPT treatment systems due to the inherent delay of processor-based signal changes. In some embodiments, circuit 510 is configured to begin terminating the delivery of treatment voltage pulses in less than 10 microseconds after identifying a fault condition. Therefore, circuit 510 is able to not only truncate treatment sequences but also truncate individual treatment pulses, thereby increasing the inherent patient safety of the EPT treatment instrument.

[0077] like Figure 5C As shown, circuit 520 includes an HV monitoring circuit. In some embodiments, HV monitoring circuit 250 may be implemented partly or entirely as circuit 520. In some embodiments, circuit 520 is configured to receive an input +HV between 0 volts and 1,500 volts and generate an output HV_MON between 0 volts and 4.983 volts. In some embodiments, HV_0V is set to 1,500 volts, and a 5-volt VCC sets the trigger to 1,512 volts. In some embodiments, HV_MON = (3.4K / (3.4K+1.025M))*HV+4.983V = 0.003306 Ohms*1500V.

[0078] like Figure 5D As shown, circuit 530 includes a capacitance monitoring circuit. In some embodiments, capacitance monitoring circuit 248 may be implemented partly or entirely as circuit 530. In some embodiments, circuit 530 is configured to receive an input CAP_V between 0 volts and 500 volts, where +HV is between 0 volts and 1,500 volts. In some embodiments, CAP_V = 0.33 * HV + . In some embodiments, CAP_MON = (10K / (10K+990K)) * CAP_V; 5V = 0.01 Ohms * CAP_V; and 5V = 0.00333 * HV + .

[0079] like Figure 5E As shown, circuit 540 includes pulse monitoring circuitry. In some embodiments, pulse monitoring circuitry 246 may be implemented partly or entirely as circuit 540. In some embodiments, circuit 540 is configured to receive an input -HV_Pulse between 0 volts and -1,500 volts and generate an output PULSE_MON between 0 volts and 4.983 volts. In some embodiments, PULSE_MON = (3.4K / (3.4K+1.025M))*HV_PULSE; and (inverted) 4.983V = 0.003306 Ohms*(-1500V).

[0080] like Figure 5F As shown, circuit 550 includes a current monitoring circuit and an impedance monitoring circuit. In some embodiments, current monitoring circuit 244 and impedance monitoring circuit 242 may be implemented partially or entirely as circuit 550. In some embodiments, the measured tissue resistance that detects a fault condition is between 0 ohms and 20 ohms. In some embodiments, IMPEDANCE_MON is between 4.1667 volts and 4.1528 volts. In some embodiments, electrically coupled to circuit 550, for example... Figure 3B The ADC shown, such as ADC2, is configured to detect a difference of 0.0138V between 11 steps. In some embodiments, open circuit = 0V; and 10K skin resistance = 1.5625V.

[0081] In some embodiments, Figure 5FThe K1 and K2 relays shown can be configured to switch between test pulse and treatment pulse / impedance monitoring and ground to separate low-voltage circuit modes and high-voltage circuit modes. For example, when K1 and K2 relays are switched to node 12, circuit 550 is in treatment pulse mode. In another example, when K1 and K2 relays are switched to 10, circuit 550 is in impedance test mode. In some embodiments, the LV impedance check is terminated when a fault is detected by executing a single software function. In some embodiments, a single software function is executed whenever any fault condition is detected, including when a fault detected during the LV impedance check is detected. The individual software functions perform the following operations in the listed order: (1) prevent (or truncate) the delivery of treatment pulses by de-asserting ENABLE_PULSE; (2) disable the HV power supply by de-asserting EN_HIGH_VOLTAGE; (3) activate the crowbar trigger by de-asserting nMICRO_CROWBAR; (4) disconnect all “needle output” relays (RE1 to RE12) by de-asserting EN_HV_1 to EN_HV_6 and EN_RTN_1 to EN_RTN_6; (5) turn off the ARM button LED by de-asserting ARM_LED_ISO; (6) wait for the high-voltage circuit to discharge to a voltage below 200Vdc by polling HV_MON; (7) reset the software-controlled crowbar trigger input by de-asserting nMICRO_CROWBAR; (8) set the identified fault to the active state; and (9) transition to the software “fault” state.

[0082] like Figure 5GAs shown, circuit 560 includes a digital potentiometer (potentiometer) circuit. In some embodiments, digital potentiometer circuit 292 may be implemented partly or entirely as circuit 560. In some embodiments, circuit 560 may be configured to provide a voltage limit via a voltage output programmed via a voltage divider, which is compared with pulse and capacitor voltages via operational amplifiers U11A and U11B, thereby allowing a crowbar trigger circuit (e.g., circuit 510) to activate if the voltage limit is exceeded. The outputs of the voltage divider are VAR_PULSE_V and VAR_CAP_V, programmed to represent pulse and capacitor overvoltage limits, respectively, for activating the crowbar trigger circuit. The outputs are compared with monitoring signals PULSE_MON and CAP_MON, respectively. If the non-inverting input is greater than the inverting input (PULSE_MON), the output nPULSE is +Vcc. nPULSE is now high and the crowbar trigger circuit is activated. D5 disables feedback. PULSE_MON must drive VAR_PULSE_V above to switch the output to -Vcc. If the non-inverting input is less than PULSE_MON, the output nPULSE is -Vcc or ISO_GND. Now, resistor R68 is connected in parallel with Rwb (the lower leg of the voltage divider), reducing the non-inverting input from VAR_PULSE_V to the lower threshold voltage VL. PULSE_MON must now be driven below VL to switch the output back to +Vcc. The diodes are used to add hysteresis during the transition from a fault state to a normal state to account for transient signal spikes, and to eliminate hysteresis for safety reasons during normal operation. In some embodiments, the ADDR1 and ADDR0 pins of component U23 are connected to GND, which sets the I2C address to 0101111. In some embodiments, Rwb = (D / 256)*Rab + 55; 1108 = (D / 256)*10000 + 55; D = 27; HEX number of the program = 0x001B. In an illustrative example embodiment, for a 400V applicator, the trip voltage is 1.33V (see Capacitor Monitoring Circuit 530); VAR_CAP_V = 1.33V; 1.33V = (12*Rwb) / (10,000 kiloohms); Rwb = 1108 ohms; and Raw = 10,000 - 1108 = 8892 ohms.

[0083] like Figure 5HAs shown, circuit 570 includes a digital potentiometer HV control circuit. In some embodiments, the digital potentiometer HV circuit 294 may be implemented partly or entirely as circuit 570. In some embodiments, the ADDR1 and ADDR0 pins of component U37 are connected to +3V3, which sets the I2C address to 0100000. In some embodiments, Rwb = (D / 256)*Rab + 55; 1108 = (D / 256)*10000 + 55; D = 27; the program's HEX number = 0x001B. In an illustrative example embodiment, for a 400V applicator, the trip voltage is 1.33V (see Capacitor Monitoring Circuit 530); VAR_CAP_V = 1.33V; 1.33V = (12*Rwb) / (10,000 kiloohms); Rwb = 1108 ohms; and Raw = 10,000 - 1108 = 8892 ohms.

[0084] like Figure 5I As shown, circuit 580 includes an HV power monitoring circuit. In some embodiments, the HV power monitoring circuit 252 may be implemented partly or entirely as circuit 580.

[0085] like Figure 5J As shown, circuit 590 includes an HV relay circuit. In some embodiments, HV relay circuit 222 may be implemented as circuit 590 in part or entirely. For example, in the case where EPE circuit 220 includes six EPE pin electrodes, HV relay circuit 222 may include circuit 590 for each of the six EPE pin electrodes.

[0086] Figure 6A , Figure 6B and Figure 6C Example pulse voltage signals are shown according to some exemplary embodiments described herein. For example... Figure 6A As shown, the user interface display screen 600 displays an example pulse voltage signal 602, which includes a rising edge 604 and a falling edge 606 of a pulse in a set of pulses. In some embodiments, the pulse monitoring and analysis circuit 276 can determine that: the width (e.g., duration) of the pulse in the set of pulses is 102.99 microseconds; the rise time of the rising edge 604 of the pulse in the set of pulses is 698 nanoseconds; and the fall time of the falling edge 626 of the pulse in the set of pulses is 1.901 microseconds.

[0087] like Figure 6B As shown, the user interface display screen 610 displays an example pulse voltage signal 612, which includes the rising edge 614 of a pulse in a set of pulses. In some embodiments, the pulse monitoring and analysis circuit 276 can determine that the rise time of the rising edge 614 of the pulse in the set of pulses is 762 nanoseconds.

[0088] like Figure 6B As shown, the user interface display screen 620 displays an example pulse voltage signal 622, which includes the falling edge 626 of a pulse in a set of pulses. In some embodiments, the pulse monitoring and analysis circuit 276 can determine that the fall time of the falling edge 626 of the pulse in the set of pulses is 1.894 microseconds.

[0089] After describing specific components of the example apparatus involved in this disclosure, the following is combined with Figure 7 Example programs are described for providing EPT treatment instruments configured to detect malfunctions.

[0090] Figure 7 Example flowchart 700 is shown, which includes example operations for detecting fault conditions while performing electroporation on cells in tissue using a set of voltage pulses generated by a voltage-based power supply, according to some example embodiments described herein. For example, in conjunction with Figure 7 The described operations can be found in the reference. Figure 1 The EPT treatment instrument 100 shown describes one or more components; through Figure 2 The device 200 shown herein; performs by any other component described herein; or any combination thereof.

[0091] As shown in block 702, device 200 includes means for continuously monitoring a set of characteristics and a set of voltage pulses of a voltage power supply, such as monitoring circuitry 240. In some embodiments, the set of characteristics may include HV voltage, capacitor voltage, pulse voltage, current, impedance voltage, HV power supply voltage, HV power supply current, any other suitable characteristics, or any combination thereof.

[0092] As shown in block 704, device 200 includes means for generating a first set of monitoring signals based on a set of characteristics, such as monitoring circuitry 240. In some embodiments, the first set of monitoring signals may include a set of analog monitoring signals, such as analog continuously monitored HV voltage signals, analog continuously monitored capacitor voltage signals, analog continuously monitored pulse voltage signals, analog continuously monitored current signals, analog continuously monitored impedance voltage signals, analog continuously monitored HV power supply voltage signals, analog continuously monitored HV power supply current signals, any other suitable analog monitoring signals, or any combination thereof. In some embodiments, the monitoring circuitry may be configured to transmit the first set of monitoring signals to any other circuitry described herein, such as an ADC circuit (e.g., ADC circuitry 296). The ADC circuitry may provide improved signal monitoring via a faster sampling ADC (e.g., 2,000,000 samples per second).

[0093] As shown in box 706, device 200 includes means for detecting a first fault condition based on a first set of monitoring signals, such as monitoring circuitry 240. The first fault condition may include simulated fault conditions, such as simulated HV overvoltage conditions, simulated capacitor overvoltage conditions, simulated pulse overvoltage signal conditions, simulated overcurrent signal conditions, any other suitable simulated fault conditions, or any combination thereof.

[0094] As shown in block 708, device 200 includes means for generating a first crowbar trigger activation signal, such as monitoring circuitry 240. In some embodiments, monitoring circuitry 240 may be configured to generate the first crowbar trigger activation signal in response to the detection of a first fault condition. In some embodiments, the first crowbar trigger activation signal may include an analog crowbar trigger activation signal, such as an HV overvoltage signal (nHV_OV), a capacitor overvoltage signal (nCAP_OV), a pulse overvoltage signal (nPULSE_OV), an overcurrent signal (nOVER_CURRENT), any other suitable analog crowbar trigger activation signal, or any combination thereof. In some embodiments, monitoring circuitry 240 may be configured to transmit the first crowbar trigger activation signal to a crowbar trigger circuit (e.g., crowbar trigger circuitry 230).

[0095] As shown in block 710, device 200 includes means for receiving a second set of monitoring signals generated based on a first set of monitoring signals, such as monitoring analysis circuit 270. The second set of monitoring signals may include a set of digital monitoring signals, such as a digitally continuously monitored HV voltage signal, a digitally continuously monitored capacitor voltage signal, a digitally continuously monitored pulse voltage signal, a digitally continuously monitored current signal, a digitally continuously monitored impedance voltage signal, a digitally continuously monitored HV power supply voltage signal, a digitally continuously monitored HV power supply current signal, any other suitable digital monitoring signal, or any combination thereof. In some embodiments, monitoring analysis circuit 270 may be configured to receive the second set of monitoring signals from any other circuit described herein, such as an ADC circuit (e.g., ADC circuit 296). For example, the first set of monitoring signals may be a set of analog monitoring signals transmitted from monitoring circuit 240 to ADC circuit 296, and the second set of monitoring signals may be a set of digital monitoring signals generated by ADC circuit 296 based on the set of analog monitoring signals and transmitted by ADC circuit 296 to monitoring analysis circuit 270.

[0096] As shown in box 712, device 200 includes means for detecting a second fault condition based on a second set of monitoring signals, such as monitoring and analysis circuitry 270. The second fault condition may include digital fault conditions, such as digital HV overvoltage condition, digital capacitor overvoltage condition, digital pulse overvoltage signal condition, digital overcurrent signal condition, any other suitable digital fault condition, or any combination thereof.

[0097] As shown in block 714, device 200 includes means for generating a second crowbar trigger activation signal, such as monitoring and analysis circuitry 270. In some embodiments, monitoring and analysis circuitry 270 may be configured to generate the second crowbar trigger activation signal in response to the detection of a second fault condition. In some embodiments, the second crowbar trigger activation signal may include a digital crowbar trigger activation signal (nMICRO_CROWBAR). In some embodiments, monitoring circuitry 240 may be configured to transmit the second crowbar trigger activation signal to a crowbar trigger circuit (e.g., crowbar trigger circuitry 230).

[0098] As shown in box 716, device 200 includes means for: receiving a first crowbar trigger activation signal or a second crowbar trigger activation signal; and for disconnecting the capacitor charging circuit from the electroporation electrode circuit in response to receiving the first crowbar trigger activation signal or the second crowbar trigger activation signal, such as monitoring and analysis circuit 270.

[0099] In some embodiments, operations 702, 704, 706, 708, 710, 712, 714, and 716 may not necessarily be performed according to... Figure 7 The sequence described herein occurs. In some embodiments, Figure 7 One or more operations described herein can occur substantially simultaneously. In some embodiments, in Figure 7 One or more additional operations may be involved before, after, or in between any of the operations shown.

[0100] As mentioned above and referenced Figure 1 , Figure 2 , Figure 3A , Figure 3B , Figure 3C , Figure 3D , Figure 4A , Figure 4B , Figure 4C , Figure 5A , Figure 5B , Figure 5C , Figure 5D , Figure 5E , Figure 5F , Figure 5G , Figure 5H , Figure 5I , Figure 5J , Figure 6A , Figure 6B , Figure 6C as well as Figure 7 As described, exemplary embodiments of this disclosure provide an EPT treatment device that includes: electroporating cells in tissue using a set of voltage pulses generated by a voltage power supply; continuously monitoring a set of characteristics of the voltage power supply and a set of voltage pulses; generating a set of analog monitoring signals based on the set of characteristics; detecting a first fault condition (e.g., overvoltage, overcurrent) based on the set of analog monitoring signals; detecting a second fault condition (e.g., overvoltage, overcurrent) based on a set of digital monitoring signals; and, in response to detecting the first fault condition or the second fault condition, disconnecting the voltage pulses and voltage power supply from the electroporation electrode needle by a crowbar trigger circuit to prevent the overvoltage and overcurrent from being applied to the patient. Therefore, exemplary embodiments of this disclosure provide: improved detection of fault conditions (e.g., overvoltage, overcurrent) through multiple redundant analog and digital circuits; and improved prevention of any overvoltage or overcurrent applied to the patient by the crowbar trigger circuit.

[0101] therefore, Figure 7Example flowcharts illustrating described operations performed according to exemplary embodiments of the present disclosure are shown. It should be understood that each block of the flowchart, and combinations of blocks in the flowchart, can be implemented by various means, including, for example, hardware, firmware, means of one or more processors, and / or circuitry associated with the execution of software comprising one or more computer program instructions. For example, the one or more programs described above can be executed by executing program code instructions. In this respect, program code instructions that enable the programs described above to execute upon execution can be stored in a non-transitory computer-readable storage medium (e.g., memory 264) of a computing device (e.g., device 200) and executed by a processor of the computing device (e.g., processor 262). In this respect, computer program instructions embodying the programs described above can be stored in the memory of a device employing embodiments of the present disclosure and executed by the processor of said device. As will be understood, any such computer program instructions can be loaded onto a computer or other programmable device (e.g., hardware) to produce a machine such that the resulting computer or other programmable device provides an embodiment of the functions specified in flowchart 700. When executed, the instructions stored in the computer-readable storage memory produce an article of art configured to implement the various functions specified in flowchart 700. Computer program instructions may also be loaded onto a computer or other programmable device to cause a series of operations to be performed on the computer or other programmable device to produce a computer-implemented process, such that the instructions executing on the computer or other programmable device provide operations for implementing the functions specified in flowchart 700. Furthermore, executing computer or other processing circuitry to perform various functions transforms the computer or other processing circuitry into a particular machine configured to perform exemplary embodiments of this disclosure.

[0102] refer to Figure 7 The flowchart operations described support combinations of means for performing a specified function and combinations of operations for performing a specified function. It should be understood that one or more operations of the flowchart, as well as combinations of operations in the flowchart, can be implemented by a computer system based on dedicated hardware or a combination of dedicated hardware and computer instructions to perform the specified function.

[0103] In some exemplary embodiments, as described below, certain operations in the operations described herein may be modified or further amplified. Furthermore, in some embodiments, additional optional operations may be included. It should be understood that each of the modifications, optional additions, or amplifications described herein may be included in the operations herein, either alone or in combination with any other features described herein.

[0104] The foregoing method descriptions and process flowcharts are provided merely as illustrative examples and are not intended to require or imply that the steps of the various embodiments must be performed in the presented order. As those skilled in the art will understand, the order of the steps in the foregoing embodiments may be performed in any order. Words such as “afterward,” “next,” “next,” and similar terms are not intended to limit the order of the steps; these words are merely used to guide the reader through the description of the method. Furthermore, any reference to singular claim elements, such as the use of the articles “a,” “an,” or “the,” should not be construed as limiting the element to the singular form and, in some cases, may be interpreted in the plural form.

[0105] While various embodiments based on the principles disclosed herein have been shown and described above, modifications can be made thereto by those skilled in the art without departing from the teachings of this disclosure. The embodiments described herein are merely representative and not intended to be limiting. Many variations, combinations, and modifications are possible and are within the scope of this disclosure. Alternative embodiments resulting from combining, integrating, and / or omitting features of one or more embodiments are also within the scope of this disclosure. Therefore, the scope of protection is not limited to the description set forth above, but is limited only by the appended claims, which include all equivalents of the subject matter of the claims. Each and every claim is incorporated into the specification as further disclosure, and the claims are embodiments of this disclosure. Furthermore, any advantages and features described above may relate to specific embodiments, but the application of such published claims should not be limited to processes and structures that achieve any or all of the foregoing advantages or have any or all of the foregoing features.

[0106] Additionally, the section headings in this document are provided in accordance with the recommendation of 37 C. FR § 1.77, or otherwise to provide an organizational prompt. These headings should not limit or characterize this disclosure as set forth in any of the claims. For example, the description of the technology in the “Background” section should not be construed as an admission that the technology described is prior art to any disclosure herein. Nor should “Summary of the Invention” be considered a limiting characterization of the disclosure set forth in the published claims. Furthermore, any reference in the singular to “Disclosure” or “Example” in this disclosure should not be used to argue that only a single point of novelty exists in this disclosure. Multiple embodiments of this disclosure may be set forth by means of the limitations of the multiple claims set forth in this disclosure, and such claims accordingly define the disclosure and its protected equivalents. In all cases, the scope of the claims should be considered in light of this disclosure and on its own merits, and should not be constrained by the headings set forth herein.

[0107] Furthermore, without departing from the scope of this disclosure, the technologies, systems, subsystems, and methods described and illustrated as independent or separate in the various embodiments may be combined or integrated with other systems, modules, technologies, or methods. Other devices or components shown or discussed as coupled or connected to each other may be indirectly coupled through some intermediate device or component, whether electrically, mechanically, or otherwise. Other variations, substitutions, and modifications will be apparent to those skilled in the art and do not depart from the scope of this disclosure.

[0108] Those skilled in the art will understand, thanks to the teachings presented in the foregoing description and associated drawings, that many modifications and other embodiments of the present disclosure set forth herein are to be realized. Although the drawings illustrate only certain components of the devices and systems described herein, it should be understood that various other components may be used in conjunction with the components and structures disclosed herein. Therefore, it should be understood that this disclosure is not intended to be limited to the specific embodiments disclosed, and that modifications and other embodiments thereof are intended to be included within the scope of the appended claims. For example, various elements or components may be combined, rearranged, or integrated in another system, or certain features may be omitted or not implemented. Furthermore, the steps in any of the methods described above do not necessarily occur in the order depicted in the drawings, and in some cases, one or more of the depicted steps may occur substantially simultaneously, or additional steps may be involved. While specific terminology is used herein, such terminology is used only in a general and descriptive sense and is not intended to be limiting.

Claims

1. A system for electroporating cells in tissue using a set of voltage pulses generated by a voltage power supply, the system comprising: A voltage generating circuit is electrically connected to a capacitor charging circuit and a monitoring circuit, wherein the voltage generating circuit is configured to The voltage power supply is generated, and The voltage power supply is transmitted to the capacitor charging circuit; as well as The capacitor charging circuit is electrically connected to the voltage generating circuit, the crowbar trigger circuit, the monitoring circuit, and the electroporation electrode circuit, and the capacitor charging circuit is configured to... Receive the voltage power supply from the voltage generation circuit. The set of voltage pulses is generated based on the voltage power supply, and The set of voltage pulses is transmitted to the electroporation electrode circuit. The monitoring circuit, wherein the monitoring circuit is electrically connected to the voltage generation circuit, the capacitor charging circuit, the monitoring and analysis circuit, and the crowbar trigger circuit, and wherein the monitoring circuit is configured to... Continuously monitor a set of characteristics of the voltage power supply and the set of voltage pulses. The first set of monitoring signals is generated based on the aforementioned set of characteristics. Transmit the first set of monitoring signals, The first fault condition is detected based on the first set of monitoring signals. In response to detecting the first fault condition, a first crowbar trigger activation signal is generated, and The activation signal of the first crowbar trigger is transmitted to the crowbar trigger circuit. The monitoring and analysis circuit, wherein the monitoring and analysis circuit is electrically connected to the crowbar trigger circuit, and wherein the monitoring and analysis circuit is configured to... Receive a second set of monitoring signals generated based on the first set of monitoring signals. The second fault condition is detected based on the second set of monitoring signals. In response to the detection of the second fault condition, a second crowbar trigger activation signal is generated, and The activation signal of the second crowbar trigger is transmitted to the crowbar trigger circuit. The crowbar trigger circuit, wherein the crowbar trigger circuit is electrically connected to the monitoring circuit and the monitoring analysis circuit, and wherein the crowbar trigger circuit is configured to... The first crowbar trigger activation signal is received from the monitoring circuit. The monitoring and analysis circuit receives the activation signal of the second crowbar trigger, and In response to receiving the first crowbar trigger activation signal or the second crowbar trigger activation signal, the capacitor charging circuit is disconnected from the electroporation electrode circuit.

2. The system according to claim 1, wherein the first set of monitoring signals is a set of analog monitoring signals, and wherein the second set of monitoring signals is a set of digital monitoring signals.

3. The system of claim 1, wherein the voltage power supply is a high-voltage HV power supply, and wherein the voltage of the HV power supply is between 1,000 volts and 1,750 volts, and wherein the ampere capacity of the HV power supply is between 40 amperes and 60 amperes.

4. The system of claim 3, wherein the voltage of the HV power supply is 1,500 volts, and wherein the ampere capacity of the HV power supply is 50 amperes.

5. The system of claim 1, wherein the duration of each voltage pulse in the set of voltage pulses is between 50 microseconds and 150 microseconds.

6. The system of claim 1, wherein the crowbar trigger circuit is configured to disconnect the capacitor charging circuit from the electroporation electrode circuit within 10 microseconds of detecting the first fault condition or the second fault condition.

7. The system of claim 1, wherein the voltage power supply is a high-voltage HV power supply, and wherein the monitoring circuit includes an HV monitoring circuit configured to: Continuously monitor the HV voltage of the HV power supply, wherein the set of characteristics includes the continuously monitored HV voltage; A first continuously monitored HV voltage signal is generated based on the continuously monitored HV voltage, wherein the first set of monitoring signals includes the first continuously monitored HV voltage signal; A first HV overvoltage condition is detected based on the first continuously monitored HV voltage signal, wherein the first fault condition is the first HV overvoltage condition; and In response to detecting the first HV overvoltage condition, a first HV overvoltage signal is generated, wherein the first crowbar trigger activation signal is the first HV overvoltage signal.

8. The system according to claim 7, wherein the monitoring and analysis circuit includes an HV monitoring and analysis circuit and a crowbar trigger control signal generation circuit. The HV monitoring and analysis circuit is configured to Receive a second continuously monitored HV voltage signal generated based on the first continuously monitored HV voltage signal, wherein the second set of monitoring signals includes the second continuously monitored HV voltage signal. The second HV overvoltage condition is detected based on the second continuously monitored HV voltage signal. The second fault condition is the second HV overvoltage condition. In response to detecting the second HV overvoltage condition, a second HV overvoltage signal is generated, and The second HV overvoltage signal is transmitted to the crowbar trigger control signal generation circuit; and The crowbar trigger control signal generation circuit is configured to The second HV overvoltage signal is received from the HV monitoring and analysis circuit. In response to receiving the second HV overvoltage signal, the second crowbar trigger activation signal is generated, and The activation signal of the second crowbar trigger is transmitted to the crowbar trigger circuit.

9. The system of claim 1, wherein the monitoring circuit includes a capacitance monitoring circuit, the capacitance monitoring circuit being configured to: The capacitor voltage of the capacitor charging circuit is continuously monitored, wherein the set of characteristics includes the continuously monitored capacitor voltage; A first continuously monitored capacitor voltage signal is generated based on the continuously monitored capacitor voltage, wherein the first set of monitoring signals includes the first continuously monitored capacitor voltage signal; The first capacitor overvoltage condition is detected based on the first continuously monitored capacitor voltage signal, wherein the first fault condition is the first capacitor overvoltage condition; and In response to detecting an overvoltage condition in the first capacitor, a first capacitor overvoltage signal is generated, wherein the first crowbar trigger activation signal is the first capacitor overvoltage signal.

10. The system according to claim 9, wherein the monitoring and analysis circuit includes a capacitance monitoring and analysis circuit and a crowbar trigger control signal generation circuit. The capacitance monitoring and analysis circuit is configured as follows: Receive a second continuously monitored capacitor voltage signal generated based on the first continuously monitored capacitor voltage signal, wherein the second set of monitoring signals includes the second continuously monitored capacitor voltage signal. The overvoltage condition of the second capacitor is detected based on the second continuously monitored capacitor voltage signal, wherein the second fault condition is the overvoltage condition of the second capacitor. In response to the detection of an overvoltage condition in the second capacitor, an overvoltage signal for the second capacitor is generated, and The overvoltage signal of the second capacitor is transmitted to the crowbar trigger control signal generation circuit; and The crowbar trigger control signal generation circuit is configured to The overvoltage signal of the second capacitor is received from the capacitance monitoring and analysis circuit. In response to receiving the second capacitor overvoltage signal, the second crowbar trigger activation signal is generated, and The activation signal of the second crowbar trigger is transmitted to the crowbar trigger circuit.

11. The system of claim 1, wherein the monitoring circuit includes a pulse monitoring circuit, the pulse monitoring circuit being configured to: Continuously monitor the pulse voltage of the set of voltage pulses, wherein the set of characteristics includes the continuously monitored pulse voltage; A first continuously monitored pulse voltage signal is generated based on the continuously monitored pulse voltage, wherein the first set of monitoring signals includes the first continuously monitored pulse voltage signal; A first pulse overvoltage condition is detected based on the first continuously monitored pulse voltage signal, wherein the first fault condition is the first pulse overvoltage condition; and In response to detecting the first pulse overvoltage condition, a first pulse overvoltage signal is generated, wherein the first crowbar trigger activation signal is the first pulse overvoltage signal.

12. The system according to claim 11, wherein the monitoring and analysis circuit includes a pulse monitoring and analysis circuit and a crowbar trigger control signal generation circuit. The pulse monitoring and analysis circuit is configured to Receive a second continuously monitored pulse voltage signal generated based on the first continuously monitored pulse voltage signal, wherein the second set of monitoring signals includes the second continuously monitored pulse voltage signal. The second pulse overvoltage condition is detected based on the second continuously monitored pulse voltage signal. The second fault condition is the second pulse overvoltage condition. In response to detecting the second pulse overvoltage condition, a second pulse overvoltage signal is generated, and The second pulse overvoltage signal is transmitted to the crowbar trigger control signal generation circuit; and The crowbar trigger control signal generation circuit is configured to The second pulse overvoltage signal is received from the pulse monitoring and analysis circuit. In response to receiving the second pulse overvoltage signal, the second crowbar trigger activation signal is generated, and The activation signal of the second crowbar trigger is transmitted to the crowbar trigger circuit.

13. The system of claim 12, wherein the pulse monitoring and analysis circuit is further configured to: Determine the rise time of the rising edge of a pulse in a set of voltage pulses; and The second pulse overvoltage condition is detected based on the rise time.

14. The system of claim 1, wherein the monitoring circuit includes a current monitoring circuit, the current monitoring circuit being configured to: Continuously monitor the current of the set of voltage pulses, wherein the set of characteristics includes the continuously monitored current; A first continuously monitored current signal is generated based on the continuously monitored current, wherein the first set of monitoring signals includes the first continuously monitored current signal; A first overcurrent condition is detected based on the first continuously monitored current signal, wherein the first fault condition is the first overcurrent condition; and In response to detecting the first overcurrent condition, a first overcurrent signal is generated, wherein the first crowbar trigger activation signal is the first overcurrent signal.

15. The system of claim 14, wherein the monitoring and analysis circuit comprises a current monitoring and analysis circuit and a crowbar trigger control signal generation circuit. The current monitoring and analysis circuit is configured as follows: Receive a second continuously monitored current signal generated based on the first continuously monitored current signal, wherein the second set of monitoring signals includes the second continuously monitored current signal. A second overcurrent condition is detected based on the second continuously monitored current signal, wherein the second fault condition is the second overcurrent condition. In response to detecting the second overcurrent condition, a second overcurrent signal is generated, and The second overcurrent signal is transmitted to the crowbar trigger control signal generation circuit; and The crowbar trigger control signal generation circuit is configured to The second overcurrent signal is received from the current monitoring and analysis circuit. In response to receiving the second overcurrent signal, the second crowbar trigger activation signal is generated, and The second overcurrent signal is transmitted to the crowbar trigger control signal generation circuit.

16. The system according to claim 1, wherein: The monitoring circuit is electrically connected to a set of relays; The monitoring circuit includes an impedance monitoring circuit, which is configured to: Generate a set of low voltage LV pulses, The set of LV pulses is transmitted to the electroporation electrode circuit. Receive a set of LV return pulses from the electroporation electrode circuit. The tissue resistance is monitored based on the set of LV return pulses. A first monitored impedance voltage signal is generated based on the monitored resistance. The fault status of the first impedance test is detected based on the first monitored impedance voltage signal; and and In response to the detection of the first impedance test fault condition, a first set of relay deactivation signals is generated, and The deactivation signal of the first group of relays is transmitted to the group of relays; The electroporation electrode circuit includes the set of relays; and Each of the relays in the group is configured to The impedance monitoring circuit receives one relay deactivation signal from the first group of relay deactivation signals, and In response to receiving one of the relay deactivation signals in the first group of relay deactivation signals, the capacitor charging circuit is disconnected from the electroporation electrode circuit.

17. The system according to claim 16, wherein: The monitoring and analysis circuit includes an impedance monitoring and analysis circuit; The impedance monitoring and analysis circuit is configured to Receive a second monitored impedance voltage signal generated based on the first monitored impedance voltage signal. Based on the second monitored impedance voltage signal, a second impedance test fault condition is detected. In response to the detection of the second monitored impedance voltage signal, a second set of relay deactivation signals is generated, and The deactivation signal for the second group of relays is transmitted to the first group of relays; and Each of the relays in the group is configured to The impedance monitoring and analysis circuit receives one relay deactivation signal from the second group of relay deactivation signals, and In response to receiving one of the relay deactivation signals in the second group of relay deactivation signals, the capacitor charging circuit is disconnected from the electroporation electrode circuit.

18. The system according to claim 1, wherein: The monitoring and analysis circuit is electrically connected to a set of relays; The monitoring and analysis circuit is further configured to In response to the detection of the second fault condition, a set of relay deactivation signals are generated, and The deactivation signal of the group of relays is transmitted to the group of relays; The electroporation electrode circuit includes the set of relays; and Each of the relays in the group is configured to The monitoring and analysis circuit receives one relay deactivation signal from the set of relay deactivation signals, and In response to receiving one of the relay deactivation signals, the capacitor charging circuit is disconnected from the electroporation electrode circuit.

19. An apparatus for electroporating cells in tissue using a set of voltage pulses generated by a voltage power supply, the apparatus comprising: A monitoring circuit, which is electrically connected to a crowbar trigger circuit, wherein the monitoring circuit is configured to Continuously monitor a set of characteristics of the voltage power supply and the set of voltage pulses. The first set of monitoring signals is generated based on the aforementioned set of characteristics. Transmit the first set of monitoring signals, The first fault condition is detected based on the first set of monitoring signals. In response to detecting the first fault condition, a first crowbar trigger activation signal is generated, and The activation signal of the first crowbar trigger is transmitted to the crowbar trigger circuit. A monitoring and analysis circuit, electrically connected to the crowbar trigger circuit, wherein the monitoring and analysis circuit is configured to... Receive a second set of monitoring signals generated based on the first set of monitoring signals. The second fault condition is detected based on the second set of monitoring signals. In response to the detection of the second fault condition, a second crowbar trigger activation signal is generated, and The activation signal of the second crowbar trigger is transmitted to the crowbar trigger circuit. The crowbar trigger circuit, wherein the crowbar trigger circuit is electrically connected to the monitoring circuit and the monitoring analysis circuit, and wherein the crowbar trigger circuit is configured to... The first crowbar trigger activation signal is received from the monitoring circuit. The monitoring and analysis circuit receives the activation signal of the second crowbar trigger, and In response to receiving the first crowbar trigger activation signal or the second crowbar trigger activation signal, the voltage power supply is disconnected from the electroporation electrode circuit.

20. A system for electroporating cells in tissue using a set of voltage pulses generated by a voltage power supply, the system comprising: A first monitoring circuit, wherein the first monitoring circuit is electrically connected to at least one of a voltage generation circuit and an electroporation electrode circuit, and wherein the first monitoring circuit is configured to: Receive the first set of monitoring signals, The first fault condition is detected based on the first set of monitoring signals. In response to the detection of the first fault condition, a first instruction configured to terminate the electroporation is transmitted; as well as A second monitoring circuit, wherein the second monitoring circuit is electrically connected to at least one of the voltage generating circuit and the electroporation electrode circuit, and wherein the second monitoring circuit is configured to: Receive the second set of monitoring signals. The second fault condition is detected based on the second set of monitoring signals. In response to the detection of the second fault condition, a second command configured to terminate the electroporation is transmitted. The first monitoring circuit is configured as follows: Continuously monitor a set of characteristics of the voltage power supply and the set of voltage pulses. The first set of monitoring signals is generated based on the aforementioned set of characteristics. Transmit the first set of monitoring signals, The first fault condition is detected based on the first set of monitoring signals. In response to detecting the first fault condition, a first crowbar trigger activation signal is generated, and The activation signal of the first crowbar trigger is transmitted to the crowbar trigger circuit. The second monitoring circuit is configured as follows: In response to the detection of the second fault condition, a second crowbar trigger activation signal is generated, and The activation signal of the second crowbar trigger is transmitted to the crowbar trigger circuit.

21. The system according to claim 20, wherein, The second set of monitoring signals is based on the first set of monitoring signals.

22. The system according to claim 20, wherein, The first monitoring circuit includes an impedance monitoring circuit, wherein the impedance monitoring circuit is configured to: Monitor the resistance of the tissue. A first monitored impedance voltage signal is generated based on the monitored resistance, and The first impedance test fault condition is detected based on the first monitored impedance voltage signal.

23. The system according to claim 22, wherein, The impedance monitoring circuit is configured as follows: Generate a set of low voltage LV pulses, The set of LV pulses is transmitted to the electroporation electrode circuit. A set of LV return pulses is received from the electroporation electrode circuit, and The tissue resistance is monitored based on the set of LV return pulses.

24. The system according to claim 20, wherein, The electroporation electrode circuit includes a relay circuit electrically connected to the electroporation electrode needle circuit, wherein the relay circuit includes a first relay and a second relay, and wherein the first monitoring circuit is configured to: In response to detecting the first fault condition, a first set of deactivation signals is generated, and The first set of deactivation signals is transmitted to the electroporation electrode circuit. The second monitoring circuit is configured as follows: In response to the detection of the second fault condition, a second set of deactivation signals is generated, and The second set of deactivation signals is transmitted to the electroporation electrode circuit.

25. The system of claim 24, wherein each of the first relay and the second relay is configured to: Receive one of the first set of deactivation signals and the second set of deactivation signals, and In response to receiving the deactivation signal, the capacitor charging circuit is disconnected from the electroporation electrode circuit.

26. The system according to claim 20, wherein, The voltage power supply is a high-voltage HV power supply, wherein the voltage of the HV power supply is between 1,000 volts and 1,750 volts.

27. The system according to claim 26, wherein, The voltage of the HV power supply is 1500 volts.

28. The system according to claim 20, wherein, The duration of each voltage pulse in the set of voltage pulses is between 50 microseconds and 150 microseconds.

29. The system according to claim 20, wherein, The capacitor charging circuit is electrically connected to the voltage generating circuit, the crowbar trigger circuit, the first monitoring circuit, and the electroporation electrode circuit, and wherein the capacitor charging circuit is configured to... Receive the voltage power supply from the voltage generation circuit. The set of voltage pulses is generated based on the voltage power supply, and The set of voltage pulses is transmitted to the electroporation electrode circuit.

30. The system according to claim 20, wherein, The first set of monitoring signals is a set of analog monitoring signals, while the second set of monitoring signals is a set of digital monitoring signals.

31. The system according to claim 20, wherein, The crowbar trigger circuit is electrically connected to the first monitoring circuit and the second monitoring circuit, and the crowbar trigger circuit is configured to: Receive the activation signal of the first crowbar trigger from the first monitoring circuit. Receive the second crowbar trigger activation signal from the second monitoring circuit, and In response to receiving either the first crowbar trigger activation signal or the second crowbar trigger activation signal, the capacitor charging circuit is disconnected from the electroporation electrode circuit.

32. The system according to claim 31, wherein, The crowbar trigger circuit is configured to disconnect the capacitor charging circuit from the electroporation electrode circuit within 10 microseconds of detecting the first fault condition or the second fault condition.

33. The system according to claim 32, wherein, The voltage power supply is a high-voltage HV power supply, and the first monitoring circuit includes a first HV monitoring circuit, which is configured to: Continuously monitor the HV voltage of the HV power supply, wherein the set of characteristics includes the continuously monitored HV voltage. A first continuously monitored HV voltage signal is generated based on the continuously monitored HV voltage, wherein the first set of monitoring signals includes the first continuously monitored HV voltage signal. A first HV overvoltage condition is detected based on the first continuously monitored HV voltage signal, wherein the first fault condition is the first HV overvoltage condition, and In response to detecting the first HV overvoltage condition, a first HV overvoltage signal is generated, wherein the first crowbar trigger activation signal is the first HV overvoltage signal.

34. The system according to claim 33, wherein, The second monitoring circuit includes a second HV monitoring circuit and a crowbar trigger control signal generation circuit. The second HV monitoring circuit is configured as follows: Based on the first continuously monitored HV voltage signal, a second continuously monitored HV voltage signal is received, wherein the second set of monitoring signals includes the second continuously monitored HV voltage signal. Based on the second continuously monitored HV voltage signal, a second HV overvoltage condition is detected. The second fault condition is the second HV overvoltage condition. In response to detecting the second HV overvoltage condition, a second HV overvoltage signal is generated, and The second HV overvoltage signal is transmitted to the crowbar trigger control signal generation circuit; and The crowbar trigger control signal generation circuit is configured as follows: Receive the second HV overvoltage signal from the second HV monitoring circuit. In response to receiving the second HV overvoltage signal, the second crowbar trigger activation signal is generated, and The activation signal of the second crowbar trigger is transmitted to the crowbar trigger circuit.

35. The system according to claim 20, wherein, The first monitoring circuit includes a first capacitance monitoring circuit, which is configured to: Continuously monitor the capacitor voltage of the capacitor charging circuit, wherein said set of characteristics includes the continuously monitored capacitor voltage. A first continuously monitored capacitor voltage signal is generated based on the continuously monitored capacitor voltage, wherein the first set of monitoring signals includes the first continuously monitored capacitor voltage signal. The overvoltage condition of the first capacitor is detected based on the first continuously monitored capacitor voltage signal, wherein the first fault condition is the overvoltage condition of the first capacitor, and In response to detecting an overvoltage condition in the first capacitor, a first capacitor overvoltage signal is generated, wherein the first crowbar trigger activation signal is the first capacitor overvoltage signal.

36. The system according to claim 35, wherein, The second monitoring circuit includes a second capacitor monitoring circuit and a crowbar trigger control signal generation circuit. The second capacitance monitoring circuit is configured as follows: A second continuously monitored capacitor voltage signal is received based on the first continuously monitored capacitor voltage signal, wherein the second set of monitoring signals includes the second continuously monitored capacitor voltage signal. The overvoltage condition of the second capacitor is detected based on the second continuously monitored capacitor voltage signal, wherein the second fault condition is the overvoltage condition of the second capacitor. In response to detecting an overvoltage condition in the second capacitor, an overvoltage signal for the second capacitor is generated, and The overvoltage signal of the second capacitor is transmitted to the crowbar trigger control signal generation circuit. as well as The crowbar trigger control signal generation circuit is configured as follows: Receive the overvoltage signal of the second capacitor from the second capacitor monitoring circuit. In response to receiving the second capacitor overvoltage signal, the second crowbar trigger activation signal is generated, and The activation signal of the second crowbar trigger is transmitted to the crowbar trigger circuit.

37. The system according to claim 20, wherein, The first monitoring circuit includes a first pulse monitoring circuit, which is configured to: Continuously monitor the pulse voltage of the set of voltage pulses, wherein the set of characteristics includes the continuously monitored pulse voltage. A first continuously monitored pulse voltage signal is generated based on the continuously monitored pulse voltage, wherein the first set of monitoring signals includes the first continuously monitored pulse voltage signal. A first pulse overvoltage condition is detected based on the first continuously monitored pulse voltage signal, wherein the first fault condition is the first pulse overvoltage condition, and In response to detecting the first pulse overvoltage condition, a first pulse overvoltage signal is generated, wherein the first crowbar trigger activation signal is the first pulse overvoltage signal.

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