Abstract: The object of the invention is to provide a method and apparatus for treating membrane-containing material with electrical fields, in vitro, and with an added treating substance. With the method, a plurality of electrodes are arrayed around the material to be treated and are connected to outputs of an electrode selection apparatus. Inputs of the electrode selection apparatus are connected to outputs of a pulse sequence generator. A treating substance is added to the membrane-containing material. Electrical pulses are applied to the electrode selection apparatus and are routed through the electrode selection apparatus in a predetermined, computer-controlled sequence to selected electrodes in the array of electrodes, whereby the membrane-containing material is treated with the added treating substance and with electrical fields. The routing of applied pulses through the electrode selection apparatus to selected electrodes can be done in an enormous number of ways.

Abstract: Delivery of metal particles to living tissue, then applying external energy that interacts with the metal particles, is found to selectively increase the energy deposition and interaction surrounding the metal particles. The method is useful to improve treatment of various conditions, since targeted cells may be selectively altered or killed. Metal particles are also loaded into cells or membrane vesicles by placing metal seed particles into the cells or vesicles, then chemically depositing additional metal on the metal seed particles. The metal particles are useful to improve imaging and therapies by their interaction with externally applied energy.

Abstract: A system for applying energy to cells so as to elicit the formation of pores, to enhance transfection, and/or cell transformation, includes a computer, a plurality of acoustic probes for controllably applying acoustic energy to batches of cells, and a robot operatively for effecting relative movement between the probes and the batches of cells. Preferably, the acoustic energy comprises ultrasonic energy, which is applied in combination with optical or electrical energy to enhance the formation of pores in surface membranes of the cells.

Abstract: A method of delivery of reactive substances that are attached to magnetizable needle-like particles using a magneto-mechanical delivery device. The subject method and device can be utilized for the delivery of reactive or other substances, such as DNA via the penetration of a target body. Such penetration of a target or multiple targets can initiate the interaction between the material contained within the target site and the chemical substances delivered by the particles into the targets. In a preferred embodiment, the subject device is portable and does not require electrical power.

Abstract: An array is placed in contact with or close proximity with an organ or tissue surface to cause electroporation for gene, protein, drug delivery in both ex vivo and in vivo applications. A low DC voltage with a short pulse duration, and long burst pulse is applied to the array. A long rest period is provided between pulse bursts to allow for cell recovery. To enable the application of a low voltage shock in a large organ with same transfection efficiency, four gene, protein and drug delivery systems are illustrated.

Abstract: The present invention involves methods and devices which enable discrete objects having a conducting inner core, surrounded by a dielectric membrane to be selectively inactivated by electric fields via irreversible breakdown of their dielectric membrane. One important application of the invention is in the selection, purification, and/or purging of desired or undesired biological cells from cell suspensions. According to the invention, electric fields can be utilized to selectively inactivate and render non-viable particular subpopulations of cells in a suspension, while not adversely affecting other desired subpopulations. According to the inventive methods, the cells can be selected on the basis of intrinsic or induced differences in a characteristic electroporation threshold, which can depend, for example, on a difference in cell size and/or critical dielectric membrane breakdown voltage.

Abstract: A system and method for processing a cells, the method comprising the steps of providing the cells to be processed in a liquid medium; and heating the liquid medium containing the cells at a rate and through a range sufficient to cause an instability in at least one of the cellular membranes. The method may be used to fuse the structure with another membranes, or to reduce the integrity of the membranes. The system atomizes a medium containing the cells into small droplets and subjects them to an environment containing steam vapor while moving at high velocity, to rapidly increase the droplet temperature to the steam temperature by release of the latent heat of vaporization.

Abstract: Provided is a method for introducing a substance into a cell, which method comprises: (a) generating one or more bubbles of a gas in a liquid medium comprising the cell, the bubbles being capable of forming a hole in the surface of the cell when one or more bubbles interact with the cell; and (b) introducing the substance into the cell.

Abstract: This invention provides a method and apparatus for selectively identifying, and targeting with an energy beam, specific cells within a mixed cell population, for the purpose of inducing a response in the targeted cells. Using the present invention, every detectable cell in a population can be identified and affected, without substantially affecting non-targeted cells within the mixture.

Abstract: A system and method for processing a lipid membrane bound structure. the method comprising the steps of providing the structure to be processed in a liquid medium; and heating the liquid medium containing the structure at a rate and through a range sufficient to cause a discrete phase transition in at least one of the membranes, such that the membranes fuse. The method may be used to fuse the structure with another structure, or to reduce the integrity of the structure. The apparatus atomizes a medium containing the structure into small droplets and subjects them to an environment containing steam vapor while moving at high velocity, to rapidly increase the droplet temperature to the steam temperature by release of the latent heat of vaporization.

Abstract: The populating method for populating a substrate with living cells provides a population with at least one populating phase and at least one perfusion phase. During the populating phase the substrate can be held in contact with the cell suspension by continuous rotation in various spatial arrangements. The populating device of the invention (10) comprises a rollable container (10a) and a removable insert in it with a means (12) for inserting the substrate being populated, such as a plastic or collagen matrix. The insert is designed so that in interaction with the inserted substrate, two liquid-tight chambers are formed within the container on opposite sides of the inserted substrate, so as to allow separate populating of both sides of the substrate. The container have liquid inlets and outlets (16) and may also have gas inlets and outlets. The rollable populating reactor (10) is inserted into a roller cabinet for certain phases of the populating.

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: A process and system for electrical extraction of intracellular matter from biological matter, and intracellular matter products formed thereby, based on preparing a mixture of biological matter featuring cells, and an electro-conductive liquid, and electrifying the mixture by transmitting controlled cycles of pulses and pauses of electrical current into the mixture by using electrodes, whereby the pulses of electrical current pierce holes into or perforate the cell membranes of the cells, enabling the release of intracellular matter for collecting and separating into target intracellular matter extract and solid waste. Pauses included in each cycle of transmitting pulses of electrical current enable firm control of electrical extraction processing conditions, including extent of extraction, temperature effects, and pressure effects, during the electrical extraction process.

Abstract: Electroporation is performed in a controlled manner in either individual or multiple biological cells or biological tissue by monitoring the electrical impedance, defined herein as the ratio of current to voltage in the electroporation cell. The impedance detects the onset of electroporation in the biological cell(s), and this information is used to control the intensity and duration of the voltage to assure that electroporation has occurred without destroying the cell(s). This is applicable to electroporation in general. In addition, a particular method and apparatus are disclosed in which electroporation and/or mass transfer across a cell membrane are accomplished by securing a cell across an opening in a barrier between two chambers such that the cell closes the opening. The barrier is either electrically insulating, impermeable to the solute, or both, depending on whether pore formation, diffusive transport of the solute across the membrane, or both are sought.

Abstract: A system and method for processing a lipid membrane bound structure, the method comprising the steps of providing the structure to be processed in a liquid medium; and beating the liquid medium containing the structure at a rate and through a range sufficient to cause a discrete phase transition in at least one of the membranes, such that the membranes fuse. The method may be used to fuse the structure with another structure, or to reduce the integrity of the structure. The apparatus atomizes a medium containing the structure into small droplets and subjects them to an environment containing steam vapor while moving at high velocity, to rapidly increase the droplet temperature to the steam temperature by release of the latent heat of vaporization.

Abstract: An electroporation apparatus for introducing exogenous material into cells is described herein. The apparatus comprises first a base member configured for holding a cell support, the cell support having a top surface portion, with the top surface portion configured for carrying adherent cells. The apparatus further comprises an electrode carrier operably associated with the base member, the electrode carrier having a bottom surface portion, a first electrode connected to the electrode carrier, and a second electrode also connected to the electrode carrier. The electrode carrier has a channel formed therein, with the channel positioned between the first electrode and the second electrode, so that exogenous material may be introduced through the channel and into contact with the cells. Methods for introducing exogenous compounds into a cell and for visually detecting the location of binding events within a cell are also disclosed.