Abstract: Methods for a new, drug-free therapy for treating solid skin tumors through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. In one embodiment of the invention, the cells are melanoma cells, and the applied nsPEFs penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin.

Abstract: A method and apparatus are provided for delivering an agent into a cell through the application of nanosecond pulse electric fields (“nsPEF's”). The method includes circuitry for delivery of an agent into a cell via known methods followed by the application of nanosecond pulse electric fields to said cell in order to facilitate entry of the agent into the nucleus of the cell. In a preferred embodiment, the present invention is directed to a method of enhancing gene expression in a cell comprising the application of nanosecond pulse electric fields to said cell. An apparatus for generating long and short pulses according to the present invention is also provided. The apparatus includes a pulse generator capable of producing a first pulse having a long duration and low voltage amplitude and a second pulse having a short duration and high voltage amplitude.

Abstract: Methods for a new, drug-free therapy for treating solid skin tumors through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. In one embodiment of the invention, the cells are melanoma cells, and the applied nsPEFs penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin.

Abstract: Disclosed herein are methods and devices for stimulating an immune response to a disease in a subject, which involves passing sub-microsecond long pulses of electric fields having an amplitude between 5 kV/cm and 68 kV/cm through an abnormal growth of a subject sufficient to suppress myeloid-derived suppressor cell (MDSC) or regulatory T cell (Treg) production, increase adenosine triphosphate (ATP) or high mobility group box 1 (HMGB1) production, or stimulate dendritic cell activation in the subject.

Abstract: Methods for treating tumors employing HSp90 inhibitors in combination with nanosecond pulsed electric fields (nsPEFs) are disclosed. The methods are directed to induce regulated cell death (RCD) in tumor cells and tissues. Further, Hsp90 inhibitors in combination with nsPEF are used at low non-toxic concentrations, thereby reducing the side-effects associated with these drugs. Additionally, nsPEFs are employed at lower electric fields and/or with fewer number of pulses than when nsPEFs are employed alone. Further, the mechanisms by which nsPEFs and Hsp90 inhibitors act upon cancer cells are different, thereby combining these treatments results in a synergistic effect.

Abstract: Methods for a new, drug-free therapy for treating solid skin tumors through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. In one embodiment of the invention, the cells are melanoma cells, and the applied nsPEFs penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin.

Abstract: A method and apparatus are provided for delivering an agent into a cell through the application of nanosecond pulse electric fields (“nsPEF's”). The method includes circuitry for delivery of an agent into a cell via known methods followed by the application of nanosecond pulse electric fields to said cell in order to facilitate entry of the agent into the nucleus of the cell. In a preferred embodiment, the present invention is directed to a method of enhancing gene expression in a cell comprising the application of nanosecond pulse electric fields to said cell. An apparatus for generating long and short pulses according to the present invention is also provided. The apparatus includes a pulse generator capable of producing a first pulse having a long duration and low voltage amplitude and a second pulse having a short duration and high voltage amplitude.

Abstract: The present disclosure describes methods for intracellular electromanipulation of proteins using nanosecond pulsed electric fields (nsPEFs). The nsPEFs have effects on proteins in addition to permeabilizing cellular membranes. The nsPEFs induce a Ca2+-dependent dissipation of the mitochondria membrane potential (??m), which is enhanced when high frequency components are present in fast rise-fall waveforms. Ca2+ is shown to have little or no effect on propidium iodide uptake as a measure of plasma membrane poration and consequently intracellular membranes. Since Ca2+-regulated events are mediated by proteins, actions of nsPEFs on proteins that regulate and/or affect the mitochondria membrane potential are possible. Given that nsPEF-induced dissipation of ??m was more effective when high frequency components were present in fast rise time waveforms, the effects on proteins are due to these high frequency components.

Abstract: Methods for a new, drug-free therapy for treating solid skin tumors through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. In one embodiment of the invention, the cells are melanoma cells, and the applied nsPEFs penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin.

Abstract: Methods for a new, drug-free therapy for treating solid skin tumors through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. In one embodiment of the invention, the cells are melanoma cells, and the applied nsPEFs penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin.

Abstract: A method and apparatus are provided for delivering an agent into a cell through the application of nanosecond pulse electric fields (“nsPEF's”). The method includes circuitry for delivery of an agent into a cell via known methods followed by the application of nanosecond pulse electric fields to said cell in order to facilitate entry of the agent into the nucleus of the cell. In a preferred embodiment, the present invention is directed to a method of enhancing gene expression in a cell comprising the application of nanosecond pulse electric fields to said cell. An apparatus for generating long and short pulses according to the present invention is also provided. The apparatus includes a pulse generator capable of producing a first pulse having a long duration and low voltage amplitude and a second pulse having a short duration and high voltage amplitude.

Abstract: Methods for forming activated platelet gels using nsPEF's and applying the activated gels to wounds, such as heart tissue after myocardial infarction. The platelets are activated by applying at least one nsPEF with a duration between about 10 picoseconds to 1 microsecond and electrical field strengths between about 10 kV/cm and 350 kV/cm.

Abstract: A medical instrument for delivering electrotherapy to tissue that includes an outer support member having a ground plate at a distal end of the outer support member, and a protrusive element having a tip that extends beyond the ground plate. A portion of the protrusive element proximate the ground plate can act as an electrical insulator and a portion of the protrusive element proximate the distal end of the protrusive element can include a first electrode. The protrusive element can be designed to penetrate into tissue below a tissue surface while a tissue contacting surface of the ground plate rests against the tissue surface. Also disclosed are systems incorporating the medical instrument and methods of electrotherapy to subsurface tissue using the medical instrument.

Abstract: A method and apparatus are provided for delivering an agent into a cell through the application of nanosecond pulse electric fields (“nsPEF's”). The method includes circuitry for delivery of an agent into a cell via known methods followed by the application of nanosecond pulse electric fields to said cell in order to facilitate entry of the agent into the nucleus of the cell. In a preferred embodiment, the present invention is directed to a method of enhancing gene expression in a cell comprising the application of nanosecond pulse electric fields to said cell. An apparatus for generating long and short pulses according to the present invention is also provided. The apparatus includes a pulse generator capable of producing a first pulse having a long duration and low voltage amplitude and a second pulse having a short duration and high voltage amplitude.

Abstract: Methods for forming activated platelet gels using nsPEF's and applying the activated gels to wounds, such as heart tissue after myocardial infarction. The platelets are activated by applying at least one nsPEF with a duration between about 10 picoseconds to 1 microsecond and electrical field strengths between about 10 kV/cm and 350 kV/cm.

Abstract: Methods and devices designed to eliminate and/or ablate cancer or other abnormal growths of cells or tissues or eliminate and/or ablate cells or tissue with abnormal functions. In particular, using sub-microsecond electric pulses to treat cancer cells by, inter alia, inducing programmed cell death or other type of cell death. These methods and devices are expected to greatly improve the prevention, treatment and management of cancer by increasing the effectiveness of cancer treatments and development of resistance to new cancer growth.

Abstract: A method and apparatus are provided for delivering an agent into a cell through the application of nanosecond pulse electric fields (“nsPEF's”). The method includes circuitry for delivery of an agent into a cell via known methods followed by the application of nanosecond pulse electric fields to said cell in order to facilitate entry of the agent into the nucleus of the cell. In a preferred embodiment, the present invention is directed to a method of enhancing gene expression in a cell comprising the application of nanosecond pulse electric fields to said cell. An apparatus for generating long and short pulses according to the present invention is also provided. The apparatus includes a pulse generator capable of producing a first pulse having a long duration and low voltage amplitude and a second pulse having a short duration and high voltage amplitude.

Abstract: Methods for a new, drug-free therapy for treating solid skin tumors through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. In one embodiment of the invention, the cells are melanoma cells, and the applied nsPEFs penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin.

Abstract: A medical instrument for delivering electrotherapy to tissue that includes an outer support member having a ground plate at a distal end of the outer support member, and a protrusive element having a tip that extends beyond the ground plate. A portion of the protrusive element proximate the ground plate can act as an electrical insulator and a portion of the protrusive element proximate the distal end of the protrusive element can include a first electrode. The protrusive element can be designed to penetrate into tissue below a tissue surface while a tissue contacting surface of the ground plate rests against the tissue surface. Also disclosed are systems incorporating the medical instrument and methods of electrotherapy to subsurface tissue using the medical instrument.

Abstract: Methods for inducing calcium mobilization in cells through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. The invention also provides a method of increasing intracellular calcium in cells through the application of nsPEFs. In one embodiment of the invention, the cells are human platelets, whereby activation and aggregation of the platelets is induced. Methods for treating an injury, trauma, or loss of blood in a subject, through the application of nsPEFs are also provided.