Abstract: The manipulator includes a support and at least one member affixed to and extending away from the support. The member has at least two differentially activatable areas of conductivity. The members are configured to establish a first electromagnetic field in vivo between selected areas of conductivity sufficient to manipulate a molecule relative to a target tissue and to establish a second, typically higher, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. Restraining means are also described for restricting movement of the members with relation to each other. One method of using the device is for enhancing the delivery of a molecule into a tissue site; another is for poration of the tissue alone or in combination with the migration. The target tissue may include a tumor, organ, or wound site.

Abstract: The present invention provides a method and apparatus adapted to facilitate the entry of a preselected molecule into the intracellular space of a cellular sample through the use of ions generated by a corona charge source. With the present method and apparatus, molecules are manipulated within cells and in the extracellular space surrounding the cells. Manipulation enhances the permeability of cell barriers to allow the subsequent introduction of molecules of interest into the interior of a cell.

Abstract: A method is presented for processing data in a multithreaded application to alleviate impaired or substandard performance conditions. Work items that are pending processing by the multithreaded application are placed into a data structure. The work items are processed by a plurality of threads within the multithreaded application in accordance with a first algorithm, e.g., first-in first-out (FIFO). A thread within the multithreaded application is configured apart from the plurality of threads such that it processes work items in accordance with a second algorithm that differs from the first algorithm, thereby avoiding the impairing condition. For example, the thread may process a pending work item only if it has a particular characteristic. The thread restricts its own processing of work items by intermittently evaluating workflow conditions for the plurality of threads; if the workflow conditions improve or are unimpaired, then the thread does not process any work items.

Abstract: The present invention is a device for electromanipulation of chemical species in vivo relative to a target tissue including a nonconductive, conformable array base adapted to be placed coincident to the target tissue, a plurality of electrode elements projecting from the array base towards the target tissue, the electrode elements addressable individually, an electrical source coupled to the plurality of electrodes, a control means interposed between the electrical source and the plurality of electrode elements and in circuit communication therein, the control means adapted to establish an electrical potential between at least two electrodes, and a delivery means adapted to introduce chemical species to the target tissue.

Abstract: A device for manipulating a molecule in vivo relative to a target tissue includes at least one elongated member having at least two discrete and separately activatable electrodes separated by an insulating material interposed therebetween. The electrodes are configured to establish at least one of a first electromagnetic field between selected electrodes sufficient to manipulate a molecule relative to a target tissue and a second, typically higher-level, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. A third electromagnetic field may also be applied to cause further translation of the molecule into an electropermeabilized cell and/or manipulated with respect to the tissue. Thus three-dimensional manipulation of the molecule relative to the target tissue may be effected to optimize a desired positioning thereof, such as entry into a cell.

Abstract: The electroporation system and method combine pulses having different characteristics for delivering molecules to cells in vivo. The pulses include a high-intensity pulse for inducing electroporation and a low-intensity pulse to induce electrophoretic molecule movement within an interstitial space, molecule adherence to a cell membrane, and electrophoretic movement of the molecule through the permeabilized membrane. The use of a high-intensity and a low-intensity pulse achieves improved delivery; reduction of intensity and/or duration of pulses for inducing electroporation; and decreased muscle stimulation, tissue damage, and patient discomfort.

Abstract: The present invention is a method of electromanipulation for effecting substantially simultaneous electroporation and electromigration of molecules into cells by applying to a cellular target a preselected electrical waveform. The preselected electrical waveform may be formed of at least one curved or linear component either increasing or decreasing in amplitude as a function of time. In a preferred embodiment of the invention the at least one component has a duration no greater than five minutes and a maximum amplitude no greater than 10,000 V/cm. Alternatively, the waveform may also include a substantially constant amplitude component interposed between the increasing and decreasing components. The substantially constant amplitude component may also be applied prior or subsequent to the at least one component.

Abstract: An apparatus for producing cell electrofusion is provided. The apparatus for producing cell fusion, the apparatus including a chamber including an insert and a cuvette, the chamber also includes a substrate, a fluid medium for containing cells to be fused in said chamber, a device for inducing migration of cells in said chamber toward one side of said substrate, and a device for inducing fusion of at least a portion of the cells.

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: A method for facilitating a delivery of a molecule into an interior space of a cell includes the steps of introducing a molecule into a target tissue comprising a cell and applying a substantially continuous low-level electric field to the target tissue. The field is applied for a duration sufficient to effect a change in porosity the cell of the target tissue sufficient to facilitate an entry of a desired molecule into an interior of the cell.

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: 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: 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: The manipulator includes a support and at least one member affixed to and extending away from the support. The member has at least two differentially activatable areas of conductivity. The members are configured to establish a first electromagnetic field in vivo between selected areas of conductivity sufficient to manipulate a molecule relative to a target tissue and to establish a second, typically higher, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. Restraining means are also described for restricting movement of the members with relation to each other. One method of using the device is for enhancing the delivery of a molecule into a tissue site; another is for poration of the tissue alone or in combination with the migration. The target tissue may include a tumor, organ, or wound site.

Abstract: A new and useful apparatus for producing cell electrofusion is provided. The apparatus comprises: a. a chamber with a substrate disposed therein, b. means for directing the cells to be fused toward one side of the substrate; and c. a device for inducing fusion of the portion of the cells.

Abstract: The manipulator includes a support and at least one member affixed to and extending away from the support. The member has at least two differentially activatable electrodes. The electrodes are configured to establish a first electromagnetic field in vivo between selected electrodes sufficient to manipulate a molecule relative to a target tissue and to establish a second, typically higher, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. One method of using the device is for enhancing the delivery of a molecule into a tissue site. In a related embodiment the device may be used to cause the electromigration of at least two components of a multicomponent reactive system into apposition to permit a reaction to occur at a desired target tissue site. The target tissue may comprise a tumor, organ, or wound site.

Abstract: A new and useful apparatus for producing cell electrofusion is provided. The apparatus comprises: a. a chamber with a substrate disposed therein, b. means for directing the cells to be fused toward one side of the substrate in so that the cells in the fluid medium are retained against the one side of the substrate with a significant portion of the cells in cell-to-cell contact with each other along said one side of the substrate, and c. a device for inducing fusion of the portion of the cells in cell-to-cell contact with each other along the predetermined portion of the one side of the substrate.

Abstract: A device for manipulating a molecule in vivo relative to a target tissue in three dimensions includes a support and at least one member affixed to and extending away from the support. The member has at least two discrete and separately activatable electrodes. The electrodes are configured to establish a first electromagnetic field between selected electrodes sufficient to manipulate a molecule relative to a target tissue. The electrodes are further configured to establish a second, typically higher-level, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. A third electromagnetic field may also be applied to cause further translation of the molecule into an electropermeabilized cell and/or manipulated with respect to the tissue. Thus three-dimensional manipulation of the molecule relative to the target tissue is effected to optimize a desired positioning thereof, such as entry into a cell.

Abstract: A method of producing a sustained localized brain immunosuppressive effect in localized tissues is achieved by transplanting Sertoli cells proximate to the brain tissue.

Abstract: A purified and isolated Sertoli cell and secretory cell hybrid, or an aggregate of these two cells, wherein the secretory cells preferably are pancreatic islet cells and chromaffin cells characterized by beinga) capable of survival in situ after transplantation;b) able to provide immunoprotection for the hybrid cells when transplanted; andc) able to provide a mechanism for prolonged viability and cellular functionality of the transplanted hybrid cells wherein the hybrid maintains both the immunoprotection characteristics of the Sertoli cell and the secretory function of the secretory cell.