Abstract: An electroporation method and apparatus generating and applying an electric field according to a user-specified pulsing and temperature profile scheme. The apparatus includes a cuvette holder with a Peltier device forming part of the electrode structures that form part of the holder. Advantageously, one such pulse includes a low voltage pulse of a first duration, immediately followed by a high voltage of a second duration, immediately followed by a low voltage of a third duration. The low voltage electroporation field accumulates molecules at the surface of a cell, the appropriately high voltage field creates an opening in the cell, and the final low voltage field moves the molecule into the cell. The molecules may be DNA, portions of DNA, chemical agents, the receiving cells may be eggs, platelets, human cells, red blood cells, mammalian cells, plant protoplasts, plant pollen, liposomes, bacteria, fungi, yeast, sperm, or other suitable cells.

Abstract: A method and apparatus are provided for introducing molecules such as genes and pharmaceutical compounds into living blood cells of a patient for therapeutic purposes. A device is placed into contact with the body of the patient for generating an electric field at a preselected location within a selected blood vessel. Preselected molecules are infused into the selected blood vessel. Simultaneously an electric signal is applied to the applied device to repeatedly subject a quantity of blood flowing within the selected blood vessel past the preselected location to electric fields of a predetermined amplitude and duration. The parameters of the electric fields are precisely controlled in order to make the walls of preselected cells in the blood transiently permeable to permit the molecules to enter said preselected cells without killing said cells.

Abstract: A method is provided for the introduction of an agent to a neoplastic cell for electroporating the cell, including contacting the cell with an electrode template apparatus. The electrode template apparatus is utilized to apply an electric field to the cell in order to introduce the agent into the cell. A method is also provided for the introduction of an agent to a tissue for electroporating a cell in the tissue, including contacting the tissue with an electrode template apparatus. The tissue is contacted with the agent and a pulse of high amplitude electric signals is applied to the cell utilizing the apparatus, for electroporation of the cell with the agent.

Abstract: An electroporation method and apparatus generating and applying an electric field according to a user-specified pulsing scheme. Advantageously, one such pulse includes a low voltage pulse of a first duration, immediately followed by a high voltage of a second duration, immediately followed by a low voltage of a third duration. The low voltage electroporation field accumulates molecules at the surface of a cell, the appropriately high voltage field creates an opening in the cell, and the final low voltage field moves the molecule into the cell. The molecules may be DNA, portions of DNA, chemical agents, the receiving cells may be eggs, platelets, human cells, red blood cells, mammalian cells, plant protoplasts, plant pollen, liposomes, bacteria, fungi, yeast, sperm, or other suitable cells. The molecules are placed in close proximity to the cells, either in the interstitial space in tissue surrounding the cells or in a fluid medium containing the cells.

Abstract: A method and apparatus for in vivo electroporation therapy. Using electroporation therapy (EPT) as described in the invention, tumors treated by a combination of electroporation using the apparatus of the invention and a chemotherapeutic agent caused regression of tumors in vivo. In one embodiment, the invention provides a method of EPT utilizing low voltage and long pulse length for inducing cell death. One embodiment of the invention includes a system for clinical electroporation that includes a needle array electrode having a "keying" element that determines the set point of the therapy voltage pulse and/or selectable array switching patterns. A number of electrode applicator designs permit access to and treatment of a variety of tissue sites. Another embodiment provides a laparoscopic needle applicator that is preferably combined with an endoscope for minimally invasive EPT.

Abstract: A method and apparatus for introducing a preselected molecule into a living cell by contacting the cell with the preselected molecule and applying a multiple series of electrical pulses to the cell. The method can be utilized ex vivo. The multiple electrical pulses generate rotating electric fields which introduce transient pores in the living cell without killing the cell. The rotating electric fields are provided in a flow through chamber apparatus having more than two electrodes. A three-step pulse process, e.g. collection, electroporation, electrophoresis, is used to introduce the preselected molecule into the cell. A mechanical means of repositioning cells between successive pulses is also provided. The apparatus can also provide a means to pulse cells at different temperatures and then after pulsing, let the cells recover for a specified residence time at another temperature.

Abstract: A method and apparatus for in vivo electroporation therapy. Using electroporation therapy (EPT) as described in the invention, tumors treated by a combination of electroporation using the apparatus of the invention and a chemotherapeutic agent caused regression of tumors in vivo. In one embodiment, the invention provides a method of EPT utilizing low voltage and long pulse length for inducing cell death. One embodiment of the invention includes a system for clinical electroporation that includes a needle array electrode having a "keying" element that determines the set point of the therapy voltage pulse and/or selectable array switching patterns. A number of electrode applicator designs permit access to and treatment of a variety of tissue sites. Another embodiment provides a laparoscopic needle applicator that is preferably combined with an endoscope for minimally invasive EPT.

Abstract: An apparatus for transdermal molecular delivery, comprises a first electrode assembly having an anode and a cathode in closely spaced relation for engaging the stratum corneum through which to apply an electric field, first power supply including a first circuit connected to the first electrode assembly for applying a pulsed electric field of sufficient amplitude to induce pores in the stratum corneum, a second electrode assembly spaced from the first electrode assembly and comprising at least one of an anode and a cathode, second power supply including a second circuit connected to the first electrode assembly and the second electrode assembly for applying a low voltage continuous electric field of a preselected polarity and sufficient amplitude to induce migration of molecules through pores in the stratum corneum.

Abstract: An electrode template apparatus, comprises a three dimensional support member having opposite surfaces, a plurality of bores extending through the support member and through the opposite surfaces, a plurality of conductors on the member separately connected to the plurality of bores, a plurality of electrodes selectively insertable in the plurality of bores so that each electrode is connected to at least one conductor for connecting the electrodes to a power supply.

Abstract: A method for in vivo electrotherapy, or electroporation-mediated therapy, using a needle array apparatus is provided. Treatment of tumors with a combination of electroporation using the apparatus of the invention, and a chemotherapeutic agent, caused regression of tumors in vivo.

Abstract: An apparatus and method for transdermal molecular delivery, comprises a first electrode assembly having an anode and a cathode in closely spaced relation for engaging the stratum corneum through which to apply an electric field, a second electrode assembly spaced from the first electrode assembly through which to apply an electric field and comprising at least one of an anode and a cathode, a first power supply including a first circuit preferably connected to the first electrode assembly for applying a pulsed electric field of sufficient amplitude to induce pores in the stratum corneum, second power supply including a second circuit connected to the first electrode assembly and the second electrode assembly for applying a low voltage continuous electric field of a preselected polarity and sufficient amplitude to induce migration of molecules through pores in the stratum corneum. The iontophoresis current density to the electrode assembly is around 0.5 mA per cm.sup.

Abstract: A method for sustained intravascular delivery via electroporation is provided. The method is useful for delivery of therapeutic compositions such as antithrombotic and anticoagulant agents. The invention also provides a catheter apparatus for introducing a composition into at least one cell in a vessel in a subject.

Abstract: An electroporation method and apparatus generating and applying an electric field according to a user-specified pulsing scheme. Advantageously, one such pulse includes a low voltage pulse of a first duration, immediately followed by a high voltage of a second duration, immediately followed by a low voltage of a third duration. The low voltage electroporation field accumulates molecules at the surface of a cell, the appropriately high voltage field creates an opening in the cell, and the final low voltage field moves the molecule into the cell. The molecules may be DNA, portions of DNA, chemical agents, the receiving cells may be eggs, platelets, human cells, red blood cells, mammalian cells, plant protoplasts, plant pollen, liposomes, bacteria, fungi, yeast, sperm, or other suitable cells. The molecules are placed in close proximity to the cells, either in the interstitial space in tissue surrounding the cells or in a fluid medium containing the cells.

Abstract: A method for producing a genetically modified plant by introducing a polynucleotide to an intact plant or plant cell(s) via electroporation, in the absence of cell wall-degrading enzymes. Genetically engineered plants produced by the method of the invention are also provided. The invention also provides a method for producing a polypeptide in an intact plant cell, including plant tissue or a whole plant by introducing a biologically active polypeptide directly into the plant.

Abstract: An electrode apparatus for the application of electroporation to a portion of the body of a patient, comprising a support member, a pair of electrodes adjustably mounted on the support member for movement toward and away from one another for positioning on opposite sides of a body portion to be electroporated, a sensing element for sensing a distance between the electrodes and generating a distance signal proportionate to the distance between the electrodes, and means responsive to said distance signal for applying pulses of high amplitude electric energy to the electrodes proportionate to the distance between the electrodes.

Abstract: An electroporation apparatus for introducing molecules into cells at a selected location within a cavity in the body of a patient includes an elongated catheter having a proximal end and a distal end and a guide wire extending from the proximal end to the distal end, an inflatable balloon carried by the distal end, the balloon having an inner inflatable bladder and an outer perforated bladder defining a chamber between the two bladders, a first electrode on an outer surface of the outer perforated bladder, a second electrode spaced from the first electrode, a remote electrode, a lumen for delivering a predetermined quantity of a fluid medium carrying preselected molecules into the chamber to be infused into the body cavity at the predetermined location; and a source of power for applying a voltage pulse between selected pairs of the electrodes for transport of the molecules by iontophoresis and/or repeatedly generating electric fields of a predetermined amplitude and duration inducing the walls of a plurality

Abstract: An electrode apparatus for the application of electroporation to a portion of the body of a patient, comprises a support member, a pair of electrodes adjustably mounted on the support member for movement toward and away from one another for positioning on opposite sides of a body portion to be electroporated, a sensing element for sensing a distance between the electrodes and generating a distance signal proportionate to the distance between said electrodes, and means responsive to said distance signal for applying pulses of high amplitude electric signal to the electrodes proportionate to the distance between said electrodes.

Abstract: A method of transdermal molecular delivery comprising molecules to be delivered mixed with particles, contacting a selected area of a skin surface with the particles and molecules, applying a pulsed electric field of sufficient amplitude and duration to induce dielectric breakdown of the stratum corneum, and applying a pressure to the molecules to force transport of the molecules through the pores in the stratum corneum into the underlying skin.

Abstract: A flow through apparatus for implanting molecules into living blood cells of a patient, comprises a housing including an elongated flow through chamber having an inlet and an outlet at opposite ends thereof, a pair of elongated spaced apart parallel electrodes disposed between the inlet and the outlet for fluid to flow therebetween, a continuous flow shunt including a pump for withdrawing blood from a patient, passing it through the flow through chamber between the electrodes and returning it to the patient, apparatus for injecting a predetermined quantity of fluid medium carrying preselected molecules into the blood after it has been drawn from the patient and before it passes through said chamber, and an electrical source for applying a predetermined electric signal of a predetermined amplitude and duration to the electrodes for generating and repeatedly applying electric fields of a predetermined amplitude and duration to the flow of the mixture of blood and fluid medium in order to make the walls of prese

Abstract: A flow through apparatus for implanting molecules into living blood cells of a patient, comprises a housing including an elongated flow through chamber having an inlet and an outlet at opposite ends thereof, a pair of elongated spaced apart parallel electrodes disposed between the inlet and the outlet for fluid to flow therebetween, a continuous flow shunt including a pump for withdrawing blood from a patient, passing it through the flow through chamber between the electrodes and returning it to the patient, apparatus for injecting a predetermined quantity of fluid medium carrying preselected molecules into the blood after it has been drawn from the patient and before it passes through said chamber, and an electrical source for applying a predetermined electric signal of a predetermined amplitude and duration to the electrodes for generating and repeatedly applying electric fields of a predetermined amplitude and duration to the flow of the mixture of blood and fluid medium in order to make the walls of prese