759 results about "Electroporation" patented technology

The present invention relates to a method and a device for transporting a molecule through a mammalian barrier membrane of at least one layer of cells comprising the steps of: ablating the membrane with an electric current from a treatment electrode; and utilizing a driving force to move the molecule through the perforated membrane.

Genetically engineered, CE7-specific redirected immune cells expressing a cell surface protein having an extracellular domain comprising a receptor which is specific for CE7, an intracellular signaling domain, and a transmembrane domain, and methods of use for such cells for cellular immunotherapy of CE7+ neuroblastoma are disclosed. In one embodiment, the immune cell is a T cell and the cell surface protein is a single chain FvFc:ζ receptor where Fv designates the V_H and V_L chains of a single chain monoclonal antibody to CE7 linked by peptide, Fc represents a hinge —C_H2—C_H3 region of a human IgG₁, and ζ represents the intracellular signaling domain of the zeta chain of human CD3. DNA constructs encoding a chimeric T-cell receptor and a method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor are also disclosed.

The present invention relates to a genetically engineered, CD19-specific chimeric T cell receptor and to immune cells expressing the chimeric receptor The present invention also relates to the use of such cells for cellular immunotherapy of CD9⁺ malignancies and for abrogating any untoward B cell function. The chimeric receptor is a single chain scFvFc:ζ receptor where scFvFc designates the extracellular domain, scFv designates the V_H and V_L chains of a single chain monoclonal antibody to CD19, Fc represents at least part of a constant region of an IgG₁, and ζ represents the intracellular signaling domain of the zeta chain of human CD3. The extracellular domain scFvFc and the intracellular domain ζ are linked by a transmembrane domain such as the transmembrane domain of CD4. In one aspect, the chimeric receptor comprises amino acids 23-634 of SEQ I DNO:2. The present invention further relates to a method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor.

The invention provides methods for inducing or increasing the vasodilation of a vessel. The invention further provides methods for inducing or increasing the flow of fluid through a vessel. An electrical impulse is applied to the vessel in order to induce or increase vessel vasodilation or to induce or increase the flow of fluid through the vessel. In a particular embodiment, a novel double-balloon catheter system incorporating electroporation technology has been designed and is used to apply the electrical impulse endoluminally.

An electroporation device which may be used to effectively facilitate the introduction of a macromolecule into cells of a selected tissue in a body or plant. The electroporation device comprises an electro-kinetic device (“EKD”) whose operation is specified by software or firmware. The EKD produces a series of programmable constant-current pulse patterns between electrodes in an array based on user control and input of the pulse parameters and allows the storage and acquisition of current waveform data. The electroporation device also comprises a replaceable electrode disk having an array of needle electrodes, a central injection channel for an injection needle, and a removable guide disk.

Methods and apparatus are provided for selective denervation of conduction pathways in the heart for the treatment of dysrhythmias, including one or more ablation or electroporation catheters having electrodes for stimulating, targeting, and ablating fat pad tissue and other cardiac tissue to selectively denervate heart tissue.

An electrical current is created across an electrically conductive medium comprising a cell which may be part of a tissue of a living organism. A first electrical parameter which may be current, voltage, or electrical impedance is measured. A second electrical parameter which may be current, voltage or a combination of both is then adjusted and/or analyzed. Adjustments are carried out to facilitate analysis and/or obtain a desired degree of electroporation. Analysis is carried out to determine characteristics of the cell membrane and/or tissue.

A method for disrupting blood flow to undesirable tissue such as cells of a cancerous or non-cancerous tumor is disclosed. It involves the placement of electrodes into or near the vicinity of vessels supplying blood to the undesirable tissue and through the application of electrical pulses causing blood flow disruption. The electric pulses irreversibly permeate the cell membranes, thereby invoking cell death. The irreversibly permeabilized cells are left in situ and are removed by the body immune system. The process may further comprise monitoring blood flow and/or infusion of a material such as a chemotherapeutic agent or marker into the blood.

A method for delivery of an agent to a cell using electroporation is disclosed. The method includes positioning a first electrode and a second electrode such that an electrical signal passed between the first electrode and the second electrode passes through the cell. The method also includes passing an electrical signal between the first electrode and the second electrode, the electrical signal having a frequency greater than about 10 kHz. In one embodiment of the method, the electrical signal has a bipolar waveform. In another embodiment of the method, the electrodes are positioned at a treatment site, e.g., a tumor, for in vivo delivery of an agent.

The invention generally relates to internal (e.g., implantable, insertable, etc.) drug delivery devices which contain the following: (a) one or more sources of one or more therapeutic agents; (b) one or more first electrodes, (c) one or more second electrodes and (d) one or more power sources for applying voltages across the first and second electrodes. The power sources may be adapted, for example, to promote electrically assisted therapeutic agent delivery within a subject, including electroporation and/or iontophoresis. In one aspect of the invention, the first and second electrodes are adapted to have tissue of a subject positioned between them upon deployment of the medical device within the subject, such that an electric field may be generated, which is directed into the tissue. Furthermore, the therapeutic agent sources are adapted to introduce the therapeutic agents into the electric field. In another aspect, the therapeutic agent sources are polymeric regions that contain one or more types of ion-conductive polymers and one or more types of charged therapeutic agents. In yet another aspect, the therapeutic agent sources are polymeric regions that contain one or more types of electrically conductive polymers and one or more types of charged therapeutic agents.

In vivo methods are provided for using an electric field to delivery therapeutic or immunizing treatment to a subject by applying non-invasive, user-friendly electrodes to the surface of the skin. Thus, therapeutic or immunizing agents can be delivered into cells of skin for local and systemic treatments or for immunization with optimal gene expression and minimal tissue damage. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.

Apparatus and methods are provided for analysis of individual particles in a microfluidic device. The methods involve the immobilization of an array of particles in suspension and the application of experimental compounds. Such methods can also include electrophysiology studies including patch clamp recording, electroporation, or both in the same microfluidic device. The apparatus provided includes a microfluidic device coupled to a multi-well structure and an interface for controlling the flow of media within the microchannel device.

Controlled-specimen-sampling oral devices are described, implanted or inserted into an oral cavity, built onto a prosthetic tooth crown, a denture plate, braces, a dental implant, or the like. The devices are replaced as needed. The controlled specimen sampling may be passive, based on a dosage form, or electro-mechanically controlled, for a high-precision, intelligent, specimen sampling. Additionally, the controlled sampling may be any one of the following: sampling in accordance with a preprogrammed regimen, sampling at a controlled rate, delayed sampling, pulsatile sampling, chronotherapeutic sampling, closed-loop sampling, responsive to a sensor's input, sampling on demand from a personal extracorporeal system, sampling regimen specified by a personal extracorporeal system, sampling on demand from a monitoring center, via a personal extracorporeal system, and sampling regimen specified by a monitoring center, via a personal extracorporeal system. Specimen collection in the oral cavity may be assisted or induced by a transport mechanism, such as any one of, or a combination of iontophoresis, electroosmosis, electrophoresis, electroporation, sonophoresis, and ablation. The oral devices require replacement at relatively long intervals of weeks or months. The oral devices and methods for controlled specimen sampling apply to humans and animals.

Cardiac electroporation ablation systems and methods in which pulsed, high voltage energy is delivered to induce electroporation of cells of cardiac tissue followed by cell rupturing. In some embodiments, the delivered energy is biphasic, having a cycle time of not more than 500 microseconds.

Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes (at physiologic pH, but can become active toward cell membranes if the environment is acidified below ca. pH 6.8), coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophereis can also be used with the disrupting agents.

Provided are methods for selecting parameters of an electrical pulse for electroporation to induce apoptosis in a tissue in need of therapeutic removal in a patient. Also provided are methods and apparatuses for treating a disease by inducing apoptosis in a tissue in need of therapeutic removal in a patient. Further provided are computer-readable media having instructions for selecting parameters of an electrical pulse for electroporation to induce apoptosis in a tissue in need of therapeutic removal in a patient.

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. Electroporation is achieved by applying a voltage between the two chambers, and diffusive transport is achieved either by a difference in solute concentration between the liquids surrounding the cell and the cell interior or by a differential in concentration between the two chambers themselves. Electric current and diffusive transport are restricted to a flow path that passes through the opening.

Disclosed is a chamber apparatus for electroporating in vitro relatively large volumes of a fluid medium carrying biological-cells-or-vesicles wherein-a reservoir for carrying said cells and vesicles is variable in its volume on demand and wherein the volume chosen is directly related to the volume of the sample to be electroporated. The apparatus has further embodiments wherein the chamber is disposable and can be operated either in isolation from a patient or connected thereto.