Abstract: The present invention provides systems, methods, and devices for electroporation-based therapies (EBTs). Embodiments provide patient-specific treatment protocols derived by the numerical modeling of 3D reconstructions of target tissue from images taken of the tissue, and optionally accounting for one or more of physical constraints or dynamic tissue properties. The present invention further relates to systems, methods, and devices for delivering bipolar electric pulses for irreversible electroporation exhibiting reduced or no damage to tissue typically associated with an EBT-induced excessive charge delivered to the tissue.

Abstract: Systems and methods are provided for transfecting immune competent cells with RNA at high efficiency and viability.

Abstract: Transfer of genetic and other materials to cells is conducted in a hands-free, automated, high throughput, continuous process. A system using a microfluidic hydrodynamic sheath flow configuration includes arrangements for pushing cells from side streams containing a cell culture medium to a central stream containing an electroporation buffer. Electroporation can be conducted in an assembly in which two or more microfluidic channels are provided in a parallel configuration and in which various layers can be stacked together to form a laminate type structure.

Abstract: An irreversible electroporation (IRE) includes setting an initial IRE protocol for applying IRE pulses by electrodes of a catheter placed in contact with tissue in an organ. A notification is issued to a user upon determining that the initial IRE protocol is expected to cause bubbles in blood. In response to the notification, user input is received from the user, that selects between the initial IRE protocol and an alternative protocol that is not expected to cause the bubbles. The IRE pulses are applied according to the initial IRE protocol or the alternative IRE protocol, depending on the user input.

Abstract: Provided are methods, systems, and kits for cell processing, e.g., for therapeutic use, such as for adoptive cell therapy. The provided methods include transduction methods, in which cells and virus are incubated under conditions that result in transduction of the cells with a viral vector. The incubation in some embodiments is carried out in an internal cavity of a generally rigid centrifugal chamber, such as a cylindrical chamber made of hard plastic, the cavity of which may have a variable volume. The methods include other processing steps, including those carried out in such a chamber, including washing, selection, isolation, culture, and formulation. In particular, the disclosure relates to method providing advantages over available processing methods, such as available methods for large-scale processing. Such advantages include, for example, reduced cost, streamlining, increased efficacy, increased safety, and increased reproducibility among different subjects and conditions.

Abstract: The invention relates to a microfluidic poration device having narrow channels slightly smaller than the width of a target cell, wherein the channels are lined with a plurality of nanospikes in a row extending down the middle of the channel, i.e. in a row parallel to the sides of the channel. In one embodiment, one channel may have 2 nanospikes (or 2 nanolancets). Thus, in particular embodiments, the invention provides microfluidic poration devices capable of simultaneously squeezing cells while piercing holes in their membranes for allowing foreign molecules into cells. The holes in porated cells spontaneously close after exiting the channels, thus entrapping the foreign molecules inside of the target cells. This porated cell population has approximately a 95% viability with greater than 50% containing at least one foreign molecule.

Abstract: A detector includes a substrate including a first surface and a second surface opposite to the first surface, a funnel-shaped recess extending from the second surface of the substrate to the first surface of the substrate, a conductive layer disposed below the first surface of the substrate, an insulating layer disposed between the substrate and the conductive layer, and a first through via extending through the conductive layer and the insulating layer, and coupled to the funnel-shaped recess.

Abstract: An exemplary apparatus, can include, for example, a circulating tumor cell (CTC) treatment arrangement, a pump arrangement configured to circulate a fluid through the CTC treatment arrangement, and an electric field generator electrically connected to the CTC treatment arrangement, and configured to apply an electric field to the fluid circulating through the CTC treatment arrangement. The pump arrangement can be a peristaltic pump, which can be configured to continuously circulate the fluid through the CTC treatment arrangement. According to another exemplary embodiment of the present disclosure, method, system and computer-accessible medium can be provided for killing at least one circulating tumor cell (CTC). Using such exemplary embodiment, blood can be pumped from a body of a patient to an electroporation chamber inside of a CTC treatment arrangement. An electric field can be applied to the blood located in the electroporation chamber in order to kill the CTC.

Abstract: An object of the invention is to provide an electroporation method for treating vesicles with exogenous material for insertion of the exogenous material into the vesicles which includes the steps of: a. retaining a suspension of the vesicles and the exogenous material in a treatment volume in a chamber which includes electrodes, wherein the chamber has a geometric factor (cm?1) defined by the quotient of the electrode gap squared (cm2) divided by the chamber volume (cm3), wherein the geometric factor is less than or equal to 0.1 cm?1, wherein the suspension of the vesicles and the exogenous material is in a medium which is adjusted such that the medium has conductivity in a range spanning 50 microSiemens/cm to 500 microSiemens/cm, wherein the suspension is enclosed in the chamber during treatment, and b. treating the suspension enclosed in the chamber with one or more pulsed electric fields.

Abstract: In accordance with the present disclosure, exposure of a sample to one or more electric pulses via capacitive coupling is described. In certain embodiments, the sample may be a biological sample to be treated or modified using the pulsed electric fields. In certain embodiments, the electric pulses may be delivered to a load using capacitive coupling. In other embodiments, the electric pulses may be bipolar pulses.

Abstract: Disclosed are apparatuses, systems, and methods for performing electroporation.

Abstract: Specifically programmed, integrated motor vehicle dangerous driving warning and control system and methods comprising at least one specialized communication computer machine including electronic artificial intelligence expert system decision making capability further comprising one or more motor vehicle electronic sensors for monitoring the motor vehicle and for monitoring activities of the driver and/or passengers including activities related to the use of cellular telephones and/or other wireless communication devices and further comprising electronic communications transceiver assemblies for communications with external sensor networks for monitoring dangerous driving situations, weather conditions, roadway conditions, pedestrian congestion and motor vehicle traffic congestion conditions to derive warning and/or control signals for warning the driver of dangerous driving situations and/or for controlling the motor vehicle driver use of a cellular telephone and/or other wireless communication devices.

Abstract: Disclosed herein is a high-density distributed three-dimensional electrode device and an associated electroporation method. The method includes applying an electric pulse of a first polarity to a first group of electrodes while simultaneously applying an electrical pulse of a second polarity to a remaining group of electrodes, and then applying an electric pulse of the first polarity on a second group of electrodes while simultaneously applying an electric pulse of the second polarity to the remaining groups of electrodes. The electrodes receiving the electric pulse of the first polarity being surrounded by the electrodes receiving the electric pulse of the second polarity, and the first polarity and the second polarity are opposite.

Abstract: Described herein are systems and methods of flow-through electroporation can comprise a chamber with a first and a second portion, wherein the first portion is configured to receive cells and the second portion is in fluid communication with the first portion and is configured to receive cells from the first portion; an electrode can be present in the first portion, second portion, or both; a porous membrane can separate the first and second portions, the porous membrane can have one or more pores, and the pores can have one or more interior surfaces configured to allow cells from the first portion to pass through to the second portion; an electric generating device in electrical communication with one or more electrodes, the membrane, or the one or more electrodes and the membrane, wherein the electric generating device is configured to deliver constant voltage or one or more electric pulses to the system.

Abstract: The present invention relates to an in vitro method for determining the transfection of a cell or group of cells, wherein said determination is performed spectroscopically. The determination comprises recording at least one Raman spectrum by means of Raman spectroscopy of the cell or group of cells. Furthermore, the present invention relates to a device for determining the transfection of a cell or group of cells, wherein the device comprises as a first unit (i) a microscope system in order to visualize the cells, as a second unit (ii) a Raman spectroscopy system in order to record a Raman spectrum of a cell or group of cells, and as a third unit (iii) an evaluation module which is coupled to the Raman spectroscopy system and which is configured to determine by means of the recorded Raman spectrum whether a cell or group of cells has been transfected.

Abstract: Methods of enhancing membrane permeabilization in a cell are provided. A method includes disposing the cell between a first electrode and a second electrode and applying a plurality of electrical pulses between the first electrode and the second electrode. In the method, the plurality of electrical pulses include at least two trains of pulses separated by an interval greater than about 10 s. Further, the amplitude of the electrical pulses is selected to be greater than about 0.2 kV/cm.

Abstract: Described is a simple plasma-based mammalian expression system that uses the RNA dependent RNA polymerase (RDRP) enzyme systems' activity for expression of recombinant proteins or RNA from viral minigenomes and rescue of recombinant viruses from cDNAs encoding entire genome(s) of negative stranded RNA viruses for use in synthesizing recombinant viruses and developing vaccines. This system will be used for expression of recombinant proteins, therapeutic RNA molecules including anti-sense and/or selecting interfering RNA and Ribozymes. This system can also be used for gene therapy and producing recombinant viruses for production of new vaccines.

Abstract: The present invention relates to a microvesicle that is derived from nucleated mammalian cells, which are smaller than the nucleated cells. The microvesicles of the present invention can be used in the delivery of a therapeutic or diagnostic substance to specific tissues or cells, and more particularly, relates to microvesicles derived from monocytes, macrophages, dendritic cells, stem cells or the like, which can be used to deliver specific therapeutic or diagnostic substances for treating and/or diagnosing tissue associated with cancer, diseased blood vessels, inflammation, or the like.

Abstract: Restenosis or neointimal formation may occur following angioplasty or other trauma to an artery such as by-pass surgery. This presents a major clinical problem which narrows the artery. The invention provides a balloon catheter with a particular electrode configuration. Also provided is a method whereby vascular cells in the area of the artery subjected to the trauma are subjected to irreversible electroporation which is a non-thermal, non-pharmaceutical method of applying electrical pulses to the cells so that substantially all of the cells in the area are ablated while leaving the structure of the vessel in place and substantially unharmed due to the non-thermal nature of the procedure.

Abstract: Methods for terminating fibrillation in a fibrillating heart employing nanosecond pulsed electric fields (nsPEFs) are disclosed. nsPEF defibrillation demonstrates its effectiveness as a new defibrillation modality, achieving reliable defibrillation with energies that are an order of magnitude lower than those needed for conventional defibrillation (millisecond shocks with mono- and bi-phasic waveforms). Tests did not reveal any negative effect of nsPEF defibrillation on cardiac tissue, in particular, cardiac tissue treated with nsPEFs does not exhibit a baseline shift in the optical transmembrane potential signal (distinctive feature that indicates electroporation), or changes in action potential duration or shape. The mechanism of nsPEF defibrillation is likely different from conventional defibrillation since it does not rely on membrane charging but on the basis of displacement currents that flow within nanoseconds after the shock is applied.

Abstract: Luminescence test measurements are conducted using an assay module having integrated electrodes with a reader apparatus adapted to receive assay modules, induce luminescence, preferably electrode induced luminescence, in the wells or assay regions of the assay modules and measure the induced luminescence.

Abstract: The present disclosure provides methods and devices for rapid and efficient modification of a variety of cell types, including mammalian cells, plant cells, archaea, yeasts, and bacteria, by novel methods of introducing exogenous materials, e.g. nucleic acids.

Abstract: The present disclosure provides a flow-through electroporation device configured for use as a stand-alone module or as one module in an automated multi-module processing system.

Abstract: Some embodiments include a high voltage waveform generator comprising: a generator inductor; a high voltage nanosecond pulser having one or more solid state switches electrically and/or inductively coupled with the generator inductor, the high voltage nanosecond pulser configured to produce a pulse burst having a burst period, the pulse burst comprising a plurality of pulses having different pulse widths; and a load electrically and/or inductively coupled with the high voltage nanosecond pulser, the generator inductor, and the generator capacitor, the voltage across the load having an output pulse with a pulse width substantially equal to the burst period and the voltage across the load varying in a manner that is substantially proportional with the pulse widths of the plurality of pulses.

Abstract: The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.

Abstract: Methods and apparatus for the reproducible, consistent and efficacious delivery of a therapeutic agent to a patient. The invention comprises means for the controlled administration of the therapeutic agent through an orifice to the patient, a plurality of penetrating electrodes arranged with a predetermined spatial relationship relative to the orifice, and means for generating an electrical signal operatively connected to the electrodes.

Abstract: A system and method for relieving hypertension includes an energy wave generator set an energy wave's frequency control mode for controlling and generating energy waves with correspond energy densities in multiple energy wave generation periods to effect on a body with hypertension, so as to relieve hypertension by the specific energy wave.

Abstract: The invention relates to methods of increasing the genetic progress of a line, breed or herd of swine through the use of sex-selected sperm cells in artificial insemination techniques. The invention also encompasses methods of artificially inseminating a swine via deep intrauterine catheter or via a laparoscopic procedure, which allow the use of reduced doses of sex-selected sperm cells.

Abstract: Surface enhanced Raman spectroscopy is employed to obtain chemical data with respect to cells while electrophysiological data relating to cell membranes is obtained using the patch clamp technique. A SERS-facilitating assembly is coupled to a micropipette and is used in conjunction with a monochromatic light source for generating scattered light. Surface enhanced Raman spectroscopy is employed to obtain the chemical data. Electrophysiological data is obtained using the same micropipette to perform the patch clamp technique.

Abstract: A cell-based biosensor array includes a base plate having a plurality of substantially transparent areas. The cell-based biosensor array also includes a flexible substrate coupled to the base plate and having disposed thereon a plurality of electrode sets, a plurality of terminal contacts, and a plurality of conductive traces. Each electrode set is disposed proximate a respective one of the substantially transparent areas, and each electrode set includes at least one electrode configured to detect an electric signal. Each terminal contact is associated with a respective one of the at least one electrode and disposed proximate a perimeter of the flexible substrate. Each conductive trace is electrically coupling a respective at least one electrode to the corresponding terminal contact. A first portion of flexible substrate including the electrode sets is disposed on a first surface of the base plate.

Abstract: A simple and low cost method of producing sealed arrays of laterally ordered nanochannels interconnected to microchannels of tunable size, over large surface areas, is disclosed. The method incorporates DNA combing and subsequent imprinting. Associated micro and macroscale inlets and outlets can be formed in the same process or manufactured later in low cost, non-cleanroom techniques. The techniques embrace two procedures, generating DNA nanostrands and translating these strands into nanoscale constructs via imprinting. Devices incorporating the novel arrays have a first microchannel, a second microchannel and a nanochannel that is substantially linear and which defines an axis. The nanochannel is connected at its open ends to the microchannels, which are aligned along the axis. Methods for precise dose delivery of agents into cells employing the devices in nanoelectroporation methods are also disclosed.

Abstract: The invention relates to a device for producing UV light. Said device provides light from light sources that operate in accordance with different physical principles. The device comprises a chamber having several gas-filled plasma chambers (11, 12), wherein the chamber has at least one area (37, 39) transparent to UV light and/or VUV light. A first group (11) of plasma chambers is filled with an ionizable gas containing mercury and a second group (12) of plasma chambers is filled with a gas that forms excimers when suitably excited.

Abstract: The present invention relates to the transient modification of cells. In particular embodiments, the cells are immune systems, such as PBMC, PBL, T (CD3+ and/or CD8+) and Natural Killer (NK) cells. The modified cells provide a population of cells that express a genetically engineered chimeric receptor which can be administered to a patient therapeutically. The present invention further relates to methods that deliver mRNA coding for the chimeric receptor to unstimulated resting PBMC, PBL, T (CD3+ and/or CD8+) and NK cells and which delivers the mRNA efficiently to the transfected cells and promotes significant target cell killing.

Abstract: The present disclosure provides a variety of systems and techniques for generating and applying plasmas and/or electric fields alone, or in combination with other therapies, to living tissue to treat different tissue conditions as well as other conditions, such as tumors, bacterial infections and the like while limiting electrical current generation within said tissue.

Abstract: The present invention relates to the transient modification of cells. In particular embodiments, the cells are immune systems, such as PBMC, PBL, T (CD3+ and/or CD8+) and Natural Killer (NK) cells. The modified cells provide a population of cells that express a genetically engineered chimeric receptor which can be administered to a patient therapeutically. The present invention further relates to methods that deliver mRNA coding for the chimeric receptor to unstimulated resting PBMC, PBL, T (CD3+ and/or CD8+) and NK cells and which delivers the mRNA efficiently to the transfected cells and promotes significant target cell killing.

Abstract: Analyte supports such as Western blots, gels, and the like is processed for purposes of detection and analysis, by placing the blot or gel on a plate and causing process fluids to oscillate across the blot or gel by intermittently rotating the plate. The plate can be inclined or flat, divided into sectors to accommodate multiple sheets, and multiple plates can be mounted to a single rotating shaft to process a large number of blots or gels simultaneously under the same protocol.

Abstract: A system and method include delivering cells of interest to multiple traps via a channel connecting the traps, maintaining a vortex flow in the traps to trap the cells of interest in the traps, providing first molecules of interest to the traps, and providing an electric field across the traps to perform electroporation of the first molecules of interest into the cells of interest in the traps.

Abstract: The present invention provides a system and method of directing, focusing, or concentrating electrical charges within a defined electric field so that these charges can be used to exert forces on cells and tissues in vivo and/or cell cultures in vitro. The present invention reduces and/or eliminates the damage at a target site that would normally be caused by an electrode that acts as a current source or sink to accomplish the same task.

Abstract: A method for sorting particles, in particular cells A and B. The method uses a single channel with only one input and only one output. A particle mix A and B in a fluid is introduced into the channel and particles within the channel are sorted.

Abstract: This invention provides novel tools for surgery on single cells and substrates/devices for delivery of reagents to selected cells. In certain embodiments the substrates comprise a surface comprising one or more orifices, where nanoparticles and/or a thin film is deposited on a surface of said orifice or near said orifice, where the nanoparticles and/or a thin film are formed of materials that heat up when contacted with electromagnetic radiation. In certain embodiments the pores are in fluid communication with microchannels containing one or more reagents to be delivered into the cells.

Abstract: A system and method include delivering cells of interest to multiple traps via a channel connecting the traps, maintaining a vortex flow in the traps to trap the cells of interest in the traps, providing first molecules of interest to the traps, and providing an electric field across the traps to perform electroporation of the first molecules of interest into the cells of interest in the traps.

Abstract: An electroporation apparatus comprising an elongated hollow member in order to provide a uniform electric field during electroporation, wherein specifically, electroporation is carried out by applying electric pulses through a couple of electrodes from both end parts of the elongated hollow member, after the hollow member is charged with fluid specimen including cells and material which would be injected into the cells.

Abstract: There are provided methods of generating antibodies in a mammal against recombinant antigens using DNA plasmids capable of expressing said antigens in cells of said mammal, comprising: injecting into tissue of said mammal a DNA plasmid comprising an encoding sequence operably linked to a promoter, electroporating said tissue with an electroporation device capable of delivering an electrical pulse effective to electroporate cells of said tissue to allow entry of said DNA plasmid and expression of said antigen, and allowing said mammal to respond to said expressed antigen in order to generate antibodies to said antigen. Furthermore, there are provided methods of isolating antibodies specific against desired antigens wherein said antibodies are generated in a mammal using DNA plasmids capable of expressing said antigens.

Abstract: Method for the selection or the processing of first particles sensitive to the application of an external stimulus including the step of producing, through the application of the external stimulus, the permeabilization of at least a selected first particle, consisting in the organization of the first particles through a first force field, to generate a second force field substantially placed in proximity of at least a selected first particle to be permeabilized.

Abstract: The present invention includes devices and methods for transfecting a cell or cell population and dynamic monitoring of cellular events. A variety of microelectronic devices are provide that incorporate functions such as electroporation, modulation of a transmembrane potential and dynamic monitoring of cellular functions and mechanisms.

Abstract: An apparatus and method for performing non-invasive treatment of the human face and body by electroporation in lieu of cosmetic surgery is provided. The apparatus comprises a high voltage pulse generator and an applicator having two or more electrodes in close mechanical and electrical contact with the patient's skin for applying the pulses to the patient's skin. The applicator may consist of two pieces with one electrode having a sharp tip and another having a flat surface. High voltage pulses delivered to the electrodes create at the tip of the sharp electrode an electric field high enough to cause death of relatively large subcutaneous fat cells by electroporation. Moving the electrode tip along the skin creates a line of necrotic subcutaneous fat cells, which later are metabolized by the body. Multiple applications of the electrode along predetermined lines on the face or neck create shrinkage of the skin and the subcutaneous fat volume underlying the treated area.

Abstract: The present invention relates to single cell array micro-chips and fabrication, electrical measurement and electroporation method thereof. The single cell array microchip comprises a substrate (1), a plurality of positioning electrodes (2) formed in an array, a plurality of measuring electrode-pairs (3) formed in an array, and a micro sample pool (4). The invention integrates cell array positioning with electrical measurement and electroporation for living cells, which is characteristic of label-free and noninvasive methods to manipulate, position particles/cells as well as further measure their electrical parameters. Therefore, single-cell-array positioning and multi-mode in-situ real-time measurement can be realized for intensive analysis. Since the positioned cells are immobile, the precision of the electrical measurement of cells is effectively improved, so is the efficiency of electroporation with lower cell mortality rate.

Abstract: The present invention concerns a device comprising (i) a composite material comprising (1) a plurality of conductive or semiconductive nanotubes, and (2) a matrix arranged between these nanotubes and (ii) means allowing said composite material to be subjected to an electric field. The present invention also concerns the uses of said device in particular to defoul or to modify a composite material and to electroporate at least one cell.

Abstract: Embodiments of the present disclosure provide a multistage procedure for treatment of biological samples (e.g., living cells with membranes, and the like) with a substance (e.g., a drug, DNA, RNA, plasmids, and other biomolecules or materials) to achieve more efficacious intracellular delivery and transfection.

Abstract: A simple and low cost method of producing sealed arrays of laterally ordered nanochannels interconnected to microchannels of tunable size, over large surface areas, is disclosed. The method incorporates DNA combing and subsequent imprinting. Associated micro and macroscale inlets and outlets can be formed in the same process or manufactured later in low cost, non-cleanroom techniques. The techniques embrace two procedures, generating DNA nanostrands and translating these strands into nanoscale constructs via imprinting. Devices incorporating the novel arrays have a first microchannel, a second microchannel and a nanochannel that is substantially linear and which defines an axis. The nanochannel is connected at its open ends to the microchannels, which are aligned along the axis. Methods for precise dose delivery of agents into cells employing the devices in nanoelectroporation methods are also disclosed.