Abstract: A pulse generation system is disclosed. The pulse generation system includes a controller, an output terminal, and a plurality of pulse generator circuits. The controller is configured to cause a driving signal pulse to be transmitted to any selected one or more of the pulse generator circuits, and to cause the driving signal pulse to not be transmitted to any selected one or more other pulse generator circuits. Each of the pulse generator circuits is configured to generate an output voltage pulse at the output terminal in response to the driving signal pulse being transmitted thereto.

Abstract: A pulse generation system is disclosed. The pulse generation system includes a controller, an output terminal, and a plurality of pulse generator circuits. The controller is configured to cause a driving signal pulse to be transmitted to any selected one or more of the pulse generator circuits, and to cause the driving signal pulse to not be transmitted to any selected one or more other pulse generator circuits. Each of the pulse generator circuits is configured to generate an output voltage pulse at the output terminal in response to the driving signal pulse being transmitted thereto.

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 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: 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: 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: 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: Techniques for treating a tumor and vaccinating against cancer are described. The techniques include treating the tumor by positioning electrodes over an interface between the tumor and non-tumor tissue and applying sub-microsecond pulsed electric fields. The positioning is facilitated by an imaginary contour line of a threshold value of the electric field. In an example, the imaginary contour line is overlaid over images that include the tumor such that the electrodes are properly positioned over the tumor. The techniques also include vaccinating against cancer by passing sub-microsecond pulsed electric fields through tumor cells of a subject sufficient to cause the tumor cells to express calreticulin on surface membranes. The tumor cells are extracted and introduced with the expressed calreticulin into the subject or another subject, thereby providing a vaccination.

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 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. 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: An electrode connectable to a pulse generator is disclosed. The electrode includes therapeutic terminals configured to deliver the pulse to a patient, first and second electrical pulse inlet holes, and a first pulse input terminal. The first pulse input terminal is in the first electrical pulse inlet hole and is spaced apart from an entrance to the first electrical pulse inlet hole by more than about 2.5 cm. Also, first pulse input terminal is connected with one or more of the therapeutic terminals. The electrode also includes a second pulse input terminal, where the second pulse input terminal is in the second electrical pulse inlet hole and is spaced apart from an entrance to the second electrical pulse inlet hole by a distance greater than about 2.5 cm. Also, the second pulse input terminal is electrically connected with one or more of the therapeutic terminals.

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 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: 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: Techniques for treating a tumor and vaccinating against cancer are described. The techniques include treating the tumor by positioning electrodes over an interface between the tumor and non-tumor tissue and applying sub-microsecond pulsed electric fields. The positioning is facilitated by an imaginary contour line of a threshold value of the electric field. In an example, the imaginary contour line is overlaid over images that include the tumor such that the electrodes are properly positioned over the tumor. The techniques also include vaccinating against cancer by passing sub-microsecond pulsed electric fields through tumor cells of a subject sufficient to cause the tumor cells to express calreticulin on surface membranes. The tumor cells are extracted and introduced with the expressed calreticulin into the subject or another subject, thereby providing a vaccination.

Abstract: Techniques for treating a tumor and vaccinating against cancer are described. The techniques include treating the tumor by positioning electrodes over an interface between the tumor and non-tumor tissue and applying sub-microsecond pulsed electric fields. The positioning is facilitated by an imaginary contour line of a threshold value of the electric field. In an example, the imaginary contour line is overlaid over images that include the tumor such that the electrodes are properly positioned over the tumor. The techniques also include vaccinating against cancer by passing sub-microsecond pulsed electric fields through tumor cells of a subject sufficient to cause the tumor cells to express calreticulin on surface membranes. The tumor cells are extracted and introduced with the expressed calreticulin into the subject or another subject, thereby providing a vaccination.

Abstract: In one aspect, methods of treating human papillomavirus (HPV)-associated growths are provided in which nano-pulse stimulation is applied at the site of a cancer. In another aspect, devices and computer systems for delivering nano-pulse stimulation for the treatment of HPV-associated growths are provided.

Abstract: The pulse applicator includes a first arm, including a first electrode, a second arm, including a second electrode, and a spacer. The first arm, the spacer, and the second arm are movably connected, and define a gap between the first arm and the second arm. The first electrode, the gap, and the second electrode are selectively alignable, and the first electrode and the second electrode are configured to deliver an electrical field across the gap in response to an electrical pulse received across the first and second electrodes.

Abstract: This disclosure relates to an in vivo treatment of tissue, for example, a skin lesion of a mammal comprising application of electrical energy to the skin lesion in a form of electrical pulses. At least one electrical pulse is applied. The pulse duration may be at least 1 nanosecond. Surface of a tissue surrounding the skin lesion may be marked to guide the device to deliver the electric pulses at substantially precise locations on the lesion surface. This treatment may prevent at least growth of the lesion.