Abstract: A micromachined cell lysis device with electrodes that are spaced by less than 10 &mgr;m from one another. The cells are attracted to the space between the.electrodes and then lysed.

Abstract: The present invention is an apparatus and method for ultrasonically treating a liquid to generate a product. The apparatus is capable of treating a continuously-flowing, or intermittently-flowing, liquid along a line segment coincident with the flow path of the liquid. The apparatus has one or more ultrasonic transducers positioned asymmetrically about the line segment. The ultrasonic field encompasses the line segment and the ultrasonic energy may be concentrated along the line segment. Lysing treatments have been successfully achieved with efficiencies of greater than 99% using ultrasound at MHz frequencies without erosion or heating problems and without the need for chemical or mechanical pretreatment, or contrast agents. The present invention overcomes drawbacks of current ultrasonic treatments beyond lysing and opens up new sonochemical and sonophysical processing opportunities.

Abstract: A loading system for providing a cell suitable for delivery of an agent to a vertebrate, the system comprise a loading module for loading a cell with an agent; and a sensitisation module in fluid communication with the loading module, the sensitisation module for sensitising a cell to an energy field, such that said cell is induced to release the agent upon exposure to said energy field. The system can be used to transform a cell, such as a red blood cell, into a delivery vehicle for delivering a therapeutic agent and/or an imaging agent to a vertebrate, and in particular, to a mammal, such as a human being.

Abstract: Methods and apparatus for modifying membranous tissue, growing cells on modified membranous tissue, and for transplantation of modified tissues and modified tissues with attached cells are provided. In particular, the invention provides methods and apparatus for modifying membranous tissue such as lens capsule tissue and inner limiting membrane tissue, for growing cells such as iris pigment epithelial (IPE) cells and retinal pigment epithelial (RPE) cells on modified membranous tissue, and for modifying membranous tissue and growing cells on biodegradable polymer substrates. A method of modifying membranous tissues comprises depositing micropatterns of biomolecules onto membranous tissue with a contacting surface such as a stamp; other methods include mechanical ablation, photoablation, ion beam ablation, and modification of membranous tissues via the action of proteolytic enzymes.

Abstract: 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.

Abstract: A micro column system is provided for high gradient magnetic field separation of macromolecules and/or cells. The system provides fast kinetics and high efficiency as well as the purity and simplicity of a column separation. A yoke provides a magnetic field to a plurality of micro columns. A separation and release process for purifying biological material on the column includes release of the biological material from magnetic particles and elution from the column while the magnetic particles are still magnetically retained by the matrix inside the column.

Abstract: Psoralen compound compositions are synthesized which have primaryamino substitutions on the 3-, 4-, 5-, and 8-positions of the psoralen, which yet permit their binding to nucleic acid of pathogens. Reaction conditions that photoactivate these psoralens result in the inactivation of pathogens which contain nucleic acid. The compounds show similar activity in test systems to 4′ and 5′ derivatives of proralen useful for inactivation of pathogens in blood products. In addition to the psoralen compositions, the invention contemplates such inactivating methods using the new psoralens.

Abstract: The recovery yields of intact plasmids from bacterial cells mechanically disrupted by various methods were measured. Bacterial cell disruption through bead milling and microfluidization were found to achieve the greatest recovery of intact plasmid. Other methods resulted in substantial DNA plasmid degradation.

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 method and system for providing real-time, biomanufacturing process monitoring and control in response to infra-red (IR) spectroscopic fingerprinting of a biomolecule. IR spectroscopy is used to fingerprint an active biomolecule in situ in a biomanufacturing process. In one embodiment, Fourier Transform Infra-red spectroscopy (FTIR) is used to determine whether an active or aged biomolecule is present in stages of a biomanufacturing process. In one preferred example, the biomanufacturing process manufactures a biomaterial in bulk. The biomanufacturing process has four stages: bioproduction, recovery, purification, and bulk storage. FTIR spectroscopy is used to monitor the optimization of each process step by providing feedback controls, and to fingerprint in real-time, in situ whether active biomolecules are present in each stage.

Abstract: Images created by electrical impedance tomography (EIT) are used to adjust one or more electrical parameters and obtain a desired degree of electroporation of cells in tissue. The parameters include current, voltage and a combination thereof. The cells are subjected to conditions such that they become permeabilized but are preferably not subjected to conditions which result in irreversible pore formation and cell death. The electroporation can analyze cell membranes, diagnose tissues and the patient as well as to move materials into and out of cells in a controlled manner.

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 apparatus for cell purification and ablation is disclosed. The present invention comprises a laser system which directs radiant energy at computer or manually selected individual cells thereby disrupting DNA, RNA and protein structure in those cells. The present invention produces a purified tissue section containing relatively intact DNA, RNA or protein from only the untreated cells. This purified sample is suitable for amplification of material by PCR or other techniques for the analysis of molecular genetic features in the selected cells of interest.

Abstract: A micromachined cell lysis device with electrodes that are spaced by less than 10 &mgr;m from one another. The cells are attracted to the space between the electrodes and then lysed.

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: A method for intracellular electro-manipulation is provided. The method includes applying at least one ultrashort electric field pulse to target cells. The ultrashort electric field pulse has sufficient amplitude and duration to modify subcellular structures in the target cells and does not exceed the breakdown field of the medium containing the target cells. The amplitude and duration of the ultrashort electric field pulse are typically insufficient to substantially alter permeability of the surface membranes of the target cells, e.g., by irreversibly disrupting the cell surface membranes. An apparatus for intracellular electro-manipulation is also provided. The apparatus includes a pulse generator capable of producing an ultrashort electric pulse output and a delivery system capable of directing the electric pulse output to target cells.

Abstract: The present invention comprises devices and methods for performing channel-less separation of cell particles by dielectrophoresis, DC high voltage-pulsed electronic lysis of separated cells, separation of desired components from crude mixtures such as cell lysates, and/or enzymatic reaction of such lysates, all of which can be conducted on a single bioelectronic chip. A preferred embodiment of the present invention comprises a cartridge (10) including a microfabricated silicon chip (12) on a printed circuit board (14) and a flow cell (16) mounted to the chip (12) to form a flow chamber. The cartridge (10) also includes output pins (22) for electronically connecting the cartridge (10) to an electronic controller. The chip (12) includes a plurality of circular microelectrodes (24) which are preferably coated with a protective permeation layer. Specific cells from various cell mixtures were separated, lysed, and enzymatically digested on the chip.

Abstract: A process and apparatus for cell purification and ablation is disclosed. The present invention comprises a laser system which directs radiant energy at computer or manually selected individual cells thereby disrupting DNA, RNA and protein structure in those cells. The present invention produces a purified tissue section containing relatively intact DNA, RNA or protein from only the untreated cells. This purified sample is suitable for amplification of material by PCR or other techniques for the analysis of molecular genetic features in the selected cells of interest.

Abstract: A process for the preparation of a vaccine from substantially viable spirochetal bacteria of Borrelia, preferably Borrelia burgdorferi having immunogenic or therapeutic properties and capable of inducing an immune or therapeutic response against Lyme Disease when administered to a patient is described. The product for use against Lyme Disease is produced by ultrasound treatment of substantially viable spirochetal bacteria of Borrelia burgdorferi. The invention produces a product and a method of treatment that can be used for the immunization and/or therapy of a patient against Lyme Disease to minimize or prevent the contraction of the disease or to treat the disease.

Abstract: A micromachined cell lysis device with electrodes that are spaced less than 100 &mgr;m from one another. The cells are attracted to the space between the electrodes and then lysed.

Abstract: The present invention comprises devices and methods for performing channel-less separation of cell particles by dielectrophoresis, DC high voltage-pulsed electronic lysis of separated cells, separation of desired components from crude mixtures such as cell lysates, and/or enzymatic reaction of such lysates, all of which can be conducted on a single bioelectronic chip. A preferred embodiment of the present invention comprises a cartridge (10) including a microfabricated silicon chip (12) on a printed circuit board (14) and a flow cell (16) mounted to the chip (12) to form a flow chamber. The cartridge (10) also includes output pins (22) for electronically connecting the cartridge (10) to an electronic controller. The chip (12) includes a plurality of circular microelectrodes (24) which are preferably coated with a protective permeation layer which prevents direct contact between any electrode and a sample introduced into the flow chamber.

Abstract: A cosmetic preparation contains peptide derivatives from &agr;-MSH, as well as other active components. A cosmetic product has the property of activating the melanogenesis and being an anti-inflammatory and acting more efficiently. The synergetically active preparation also includes a combination of a peptide derivative corresponding to the formula (Lip)X-His-Phe-Arg-Y in a ratio of 0.05 mg to 2.5 mg of a pure peptide derivative per kg of the total mass, while the peptide derivative is mixed with xanthine in a ratio of 0.5 to 2 mol per 100 mol of peptide. Also there is at least 0.5 wt % of a mixture of enzymes and vitamins, containing at least 150 U/ml of superoxide dismutase. Also present are auxiliary agents and carrier agents in a ratio of 65 to 99.5 wt %, and possibly other active components.

Abstract: The invention describes a method for the isolation of components from samples, particularly large molecular weight DNA from biological samples. The method involves the application of controlled oscillatory mechanical energy to the sample for short periods of time of about 5 to 60 seconds to lyse the sample and release the component(s) from the sample, followed by standard isolation methods. In preferred embodiments, the method includes the use of a spherical particle for applying the mechanical energy.

Abstract: An autoimmune vaccine is provided for administration to human patients to alleviate the symptoms of autoimmune diseases such as rheumatoid arthritis. The vaccine comprises an aliquot of the patient's blood, containing, inter alia, leukocytes having upregulated expression of various cell surface markers and lymphocytes containing decreased amounts of certain stress proteins. It is produced by subjecting the blood aliquot extracorporeally to certain stressors, namely oxidizing agents, UV radiation and elevated temperature.