Abstract: Flexible catheters adapted to be inserted into a body to deliver high-voltage, fast (e.g., microsecond, sub-microsecond, nanosecond, picosecond, etc.) electrical energy to target tissue may include a plurality of conductive layers, that may be coaxial. These catheters and method of using them to treat tissue are configured to reduce or avoid arcing.

Abstract: Described herein are apparatuses (e.g., systems and devices) and methods of delivering nanosecond pulsed electrical fields (nsPEF). In particular, these apparatuses and methods may provide enhanced safety and robust operation over even very short (e.g., nanosecond and sub-nanosecond pulses) and high voltage pulsing; these benefits may be accomplished by multi-functional isolation of various subsystems and components of the apparatus, even including the low-voltage, control and command portions of the apparatus with extremely low capacitance, high voltage isolation.

Abstract: Methods and apparatuses (e.g., devices, instruments and systems, including applicator handles for use with pulse generators) for automatically and/or mechanically setting impedance matching for connecting the applicator handle with different electrode tips. These methods and apparatuses may be useful for applying therapeutic energy, including but not limited to short, high field strength electric pulses, while avoiding the risk of arcing or otherwise harming the tissue.

Abstract: Described herein are apparatuses and methods for applying high voltage, sub-microsecond (e.g., nanosecond range) pulsed output to a biological material, e.g., tissues, cells, etc., using a high voltage (e.g., MOSFET) gate driver circuit having a high voltage isolation and a low inductance. In particular, described herein are multi-core pulse transformers comprising independent transformer cores arranged in parallel on opposite sides of a substrate. The transformer cores may have coaxial primary and secondary windings. Also describe are pulse generators including multi-core pulse transformers arranged in parallel (e.g., on opposite sides of a PCB) to reduce MOSFET driver gate inductance.

Abstract: A sub-microsecond pulsed electric field generator is disclosed. The field generator includes a controller, which generates a power supply control signal and generates a pulse generator control signal, and a power supply, which receives the power supply control signal and generates one or more power voltages based on the received power supply control signal. The field generator also includes a pulse generator which receives the power voltages and the pulse generator control signal, and generates one or more pulses based on the power voltages and based on the pulse generator control signal. In some embodiments, the controller receives feedback signals representing a value of a characteristic of or a result of the pulses and generates at least one of the power supply control signal and the pulse generator control signal based on the received feedback signals.

Abstract: A pulse generator discharge circuit is disclosed. The circuit includes one or more discharge stages, each discharge stage including a plurality of control input terminals. The circuit also includes first and second discharge terminals, and a plurality of serially connected switches electrically connected between the first and second discharge terminals, where a conductive state of each of the switches is controlled by a control signal. The circuit also includes a plurality of inductive elements configured to generate the control signals for the serially connected switches, where each inductive element is configured to generate a control signal for one of the serially connected switches in response to one or more input signals at one or more of the control input terminals, and where each of the serially connected switches is configured to receive a control signal from a respective one of the inductive elements.

Abstract: A sub-microsecond pulsed electric field generator is disclosed. The field generator includes a controller, which generates a power supply control signal and generates a pulse generator control signal, and a power supply, which receives the power supply control signal and generates one or more power voltages based on the received power supply control signal. The field generator also includes a pulse generator which receives the power voltages and the pulse generator control signal, and generates one or more pulses based on the power voltages and based on the pulse generator control signal. In some embodiments, the controller receives feedback signals representing a value of a characteristic of or a result of the pulses and generates at least one of the power supply control signal and the pulse generator control signal based on the received feedback signals.

Abstract: To distribute electrical treatment to a treatment area of a patient, described herein are electrical therapy devices, methods of their operation and methods for delivery of the electrical therapy to the patient. In some embodiments, the electrical therapy device comprises an electrode assembly that includes at least two electrodes, and a conductive spacer positioned between the electrodes. Methods of selection of the electrical therapy devices and methods of their operation are also provided.

Abstract: Described herein are methods and systems for using the treatment tip apparatuses and high-voltage connectors with robotic surgical systems. For example, retractable treatment tip apparatuses (e.g., devices, systems, etc.) including one, or more preferably a plurality, of electrodes that are protected by a housing (which may be retractable) until pressed against the tissue for deployment of the electrodes and delivery of a therapeutic treatment, are disclosed. In particular, these apparatuses may include a plurality of treatment needle electrodes and may be configured for the delivery of nanosecond pulsed electric fields. Also described herein are high-voltage connectors configured to provide high-voltage energy, such as nsPEF pulses, from a generator to the retractable treatment tip apparatuses.

Abstract: Methods and apparatuses for treating a tissue with an electric treatment by rotating a pattern of electrodes partway through a treatment is disclosed. Also described herein are methods and apparatuses to treat tissue, including treating skin disorders, by selectively de-nucleating epidermal cells without provoking a significant inflammatory response, e.g., without increasing the density of leukocytes in the treated skin, and without affecting the non-cellular components of the dermis.

Abstract: Electrodes that are configured to apply energy within the tissue while moving relative to the tissue. The apparatuses (devices, assemblies, systems) described herein may be configured with one or more electrodes that may move slightly in oscillatory movement and/or rotation relative to the tissue. The apparatuses described herein may be used to apply energy to a patient while minimizing or preventing the unintended modification of the tissue adjacent to the electrode, such as by arcing.

Abstract: Flexible catheters adapted to be inserted into a body to deliver high-voltage, fast (e.g., microsecond, sub-microsecond, nanosecond, picosecond, etc.) electrical energy to target tissue may include a plurality of conductive layers, that may be coaxial. These catheters and method of using them to treat tissue are configured to reduce or avoid arcing.

Abstract: Described herein are apparatuses and methods for applying high voltage, sub-microsecond (e.g., nanosecond range) pulsed output to a biological material, e.g., tissues, cells, etc., using a high voltage (e.g., MOSFET) gate driver circuit having a high voltage isolation and a low inductance. In particular, described herein are multi-core pulse transformers comprising independent transformer cores arranged in parallel on opposite sides of a substrate. The transformer cores may have coaxial primary and secondary windings. Also describe are pulse generators including multi-core pulse transformers arranged in parallel (e.g., on opposite sides of a PCB) to reduce MOSFET driver gate inductance.

Abstract: A handheld, therapeutic electrode and connector that are compatible with high voltages from a pulse generator are disclosed. The electrode includes therapeutic terminals on a tip configured to deliver high voltage pulses safely to a patient. The electrode includes sleeves, bosses, wiring channels, and other features that maximize a minimum clearance distance (across non-conductive surfaces) and air clearance between conductive connectors themselves or the connectors and a user, thus preventing dangerous arcing. Internal surfaces and seams are taken into account. The connector and its mating outlet can include similar features to maximize clearance distance. Skirts, skirt holes, and finger stops are also employed, and they can be on either the connector or outlet, or the tip or handle of the electrode.

Abstract: Methods and apparatuses for treating a tissue with an electric treatment by rotating a pattern of electrodes partway through a treatment is disclosed. Also described herein are methods and apparatuses to treat tissue, including treating skin disorders, by selectively de-nucleating epidermal cells without provoking a significant inflammatory response, e.g., without increasing the density of leukocytes in the treated skin, and without affecting the non-cellular components of the dermis.

Abstract: A handheld, therapeutic electrode and connector that are compatible with high voltages from a pulse generator are disclosed. The electrode includes therapeutic terminals on a tip configured to deliver high voltage pulses safely to a patient. The electrode includes sleeves, bosses, wiring channels, and other features that maximize a minimum clearance distance (across non-conductive surfaces) and air clearance between conductive connectors themselves or the connectors and a user, thus preventing dangerous arcing. Internal surfaces and seams are taken into account. The connector and its mating outlet can include similar features to maximize clearance distance. Skirts, skirt holes, and finger stops are also employed, and they can be on either the connector or outlet, or the tip or handle of the electrode.

Abstract: Described herein are treatment tip apparatuses (e.g., devices, systems, etc.) including one, or more preferably a plurality, of electrodes that are protected by an electrode partition, such as an electrode housing (which may be retractable) until pressed against the tissue for deployment of the electrodes and delivery of a therapeutic treatment. In particular, these apparatuses may include a plurality of treatment electrodes (e.g., needle electrodes) and be configured for the delivery of nanosecond pulsed electric fields.

Abstract: A sub-microsecond pulsed electric field generator is disclosed. The field generator includes a controller, which generates a power supply control signal and generates a pulse generator control signal, and a power supply, which receives the power supply control signal and generates one or more power voltages based on the received power supply control signal. The field generator also includes a pulse generator which receives the power voltages and the pulse generator control signal, and generates one or more pulses based on the power voltages and based on the pulse generator control signal. In some embodiments, the controller receives feedback signals representing a value of a characteristic of or a result of the pulses and generates at least one of the power supply control signal and the pulse generator control signal based on the received feedback signals.

Abstract: Nanosecond pulsed electric field (nsPEF) treatments of a tumor are adjusted based on a size and type of the tumor to stimulate an immune response against the tumor and other tumors in the subject. Calreticulin expression on tumor cells can be detected to confirm treatment. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated by directly treating a tumor that is most accessible. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and/or strength of tumors and/or a quantity of tumors in the subject.

Abstract: A sub-microsecond pulsed electric field generator is disclosed. The field generator includes a controller, which generates a power supply control signal and generates a pulse generator control signal, and a power supply, which receives the power supply control signal and generates one or more power voltages based on the received power supply control signal. The field generator also includes a pulse generator which receives the power voltages and the pulse generator control signal, and generates one or more pulses based on the power voltages and based on the pulse generator control signal. In some embodiments, the controller receives feedback signals representing a value of a characteristic of or a result of the pulses and generates at least one of the power supply control signal and the pulse generator control signal based on the received feedback signals.