22090 results about "Biophysics" patented technology

Disclosed herein are biointerface membranes including a macro-architecture and a micro-architecture co-continuous with and bonded to and / or located within at least a portion of the macro-architecture. The macro- and micro-architectures work together to manage and manipulate the high-level tissue organization and the low-level cellular organization of the foreign body response in vivo, thereby increasing neovascularization close to a device-tissue interface, interfering with barrier cell layer formation, and providing good tissue anchoring, while reducing the effects of motion artifact, and disrupting the organization and / or contracture of the FBC. The biointerface membranes of the preferred embodiments can be utilized with implantable devices such as devices for the detection of analyte concentrations in a biological sample (for example, from a body), cell transplantation devices, drug delivery devices, electrical signal delivering or measuring devices, and / or combinations thereof.

The present invention discloses devices and methods of performing high throughput screening of the physiological response of cells to biologically active compounds and methods of combining high-throughput with high-content spatial information at the cellular and subcellular level as well as temporal information about changes in physiological, biochemical and molecular activities. The present invention allows multiple types of cell interactions to be studied simultaneously by combining multicolor luminescence reading, microfluidic delivery, and environmental control of living cells in non-uniform micro-patterned arrays.

Multimolecular devices and drug delivery systems prepared from synthetic heteropolymers, heteropolymeric discrete structures, multivalent heteropolymeric hybrid structures, aptameric multimolecular devices, multivalent imprints, tethered specific recognition devices, paired specific recognition devices, nonaptameric multimolecular devices and immobilized multimolecular structures are provided, including molecular adsorbents and multimolecular adherents, adhesives, transducers, switches, sensors and delivery systems. Methods for selecting single synthetic nucleotides, shape-specific probes and specifically attractive surfaces for use in these multimolecular devices are also provided. In addition, paired nucleotide-nonnucleotide mapping libraries for transposition of selected populations of selected nonoligonucleotide molecules into selected populations of replicatable nucleotide sequences are described.

Methods and materials for culturing primate-derived primordial stem cells are described. In one embodiment, a cell culture medium for growing primate-derived primordial stem cells in a substantially undifferentiated state is provided which includes a low osmotic pressure, low endotoxin basic medium that is effective to support the growth of primate-derived primordial stem cells. The basic medium is combined with a nutrient serum effective to support the growth of primate-derived primordial stem cells and a substrate selected from the group consisting of feeder cells and an extracellular matrix component derived from feeder cells. The medium further includes non-essential amino acids, an anti-oxidant, and a first growth factor selected from the group consisting of nucleosides and a pyruvate salt.

The present invention provides a method of extracting and recovering embryonic-like stem cells, including, but not limited to pluripotent or multipotent stem cells, from an exsanguinated human placenta. A placenta is treated to remove residual umbilical cord blood by perfusing an exsanguinated placenta, preferably with an anticoagulant solution, to flush out residual cells. The residual cells and perfusion liquid from the exsanguinated placenta are collected, and the embryonic-like stem cells are separated from the residual cells and perfusion liquid. The invention also provides a method of utilizing the isolated and perfused placenta as a bioreactor in which to propagate endogenous cells, including, but not limited to, embryonic-like stem cells. The invention also provides methods for propagation of exogenous cells in a placental bioreactor and collecting the propagated exogenous cells and bioactive molecules therefrom.

The present invention provides methods for making heteromultimeric molecules, such as bispecific antibodies, and compositions comprising said molecules. The method includes introducing mutations in amino acids that are in contact at the interface of two polypeptides, such that the electrostatic interaction between the ion pairs is altered.

The invention relates to devices and methods for nanopore sequencing. The invention includes arrays of nanopores having incorporated electronic circuits, for example, in CMOS. In some cases, the arrays of nanopores comprise resistive openings for isolating the electronic signals for improved sequencing. Methods for controlling translocation of through the nanopore are disclosed.

An apparatus for the continuous measurement of glucose and lactate in interstitial fluids including a glucose measurement cell, an A / D conversion block, a memory block and a bi-directional communication between the interface block and an external calculation unit.

A method of processing an acellular tissue matrix to give a particulate acellular tissue matrix includes: cutting sheets of dry acellular tissue matrix into strips; cryofracturing the dry acellular tissue matrix strips at cryogenic temperatures; separating the resulting particles by size at cryogenic temperatures; and freeze drying the fraction of particles desired size to remove any moisture that may have been absorbed to give a dry particulate acellular tissue matrix. Rehydration of the dry particulate acellular tissue matrix may take place just prior to use. The particulate acellular tissue may be applied to a recipient site, by way of injection, spraying, layering, packing, in-casing or combinations thereof. The particulate acellular tissue may further include growth and stimulating agents selected from epidermal growth factor, fibroblast growth factor, nerve growth factor, keratinocyte growth factor, platelet derived growth factor, vasoactive intestinal peptide, stem cell factor, bone morphogetic proteins, chondrocyte growth factor and combinations thereof. Other pharmaceutically active compounds may be combined with the rehydrated particulate material including: analgesic drugs; hemostatic drugs; antibiotic drugs; local anesthetics and the like to enhance the acceptance of the implanted particulate material. The particulate material product may also be combined with stem cells selected from mesenchymal stem cells, epidermal stem cells, cartilage stem cells, hematopoietic stem cells and combinations thereof.

The present invention provides novel encapsulation compositions and methods. In particular, the invention relates to fluorescent capsule compositions, which consists of a layer of a polymer shell enclosing one or more fluorescent materials such as fluorescent microspheres and which are capable of emitting at least two distinct fluorescent signals. Also provided are methods for their preparation. The compositions and methods of this invention are useful in a variety of applications, including preparation of multiplexed arrays for industrial, chemical, immunological, and genetic manipulation and analysis especially as related but not limited to flow cytometry.

The present invention relates generally to scFc molecules. The scFc molecules comprise at least two Fc regions and at least one linker, and can be produced in a variety of single chain configurations. The scFc molecules can further comprise at least one binding entity and / or at least one functional molecule. Binding entities can be fused to the scFc molecule in a variety of configurations. The present invention also relates generally to methods for making such molecules and methods for their use. The scFc molecules provided herein can be recombinantly produced. Also provided are monovalent forms of the scFc molecules that have an equivalent or superior ADCC and / or CDC response than do bivalent molecules targeting the same antigens. Provided herein are improved antigen binding compositions. Methods for using the scFc molecules of the present inventions are provided

A method is disclosed for enhanced vaccination and genetic vaccination of mammals. The vaccination is accomplished by delivering molecules such as proteins and nucleic acids into skeletal muscle and other cells residing in the skeletal muscle in vivo. The protein or nucleic acid is first injected into the muscle at one or multiple sites. Immediately or shortly after injection, electrodes are placed flanking the injection site and a specific amount of electrical current is passed through the muscle. The electrical current makes the muscle permeable, thus allowing the pharmaceutical drug or nucleic acid to enter the cell. The efficiency of transfer permits robust immune responses using DNA vaccines and produces sufficient secreted proteins for systemic biological activity to be observed.

The present invention provides cell populations that are enriched for mesendoderm and mesoderm, and cell populations that are enriched for endoderm. The cell populations of the invention are useful for generating cells for cell replacement therapy.

In vivo or in vitro monitoring of chemical and biochemical species (e.g., pH, or glucose levels) in the interstitial fluid of patients or in a sample of a fluid to be analyzed is provided by a probe (10, 70, 210, 270). For in vivo monitoring, the probe is readily inserted by a minimally invasive method. Optical or electrochemical sensing methods are employed to detect a physical or chemical change, such as pH, color, electrical potential, electric current, or the like, which is indicative of the concentration of the species or chemical property to be detected. Visual observation by the patient may be sufficient to monitor certain biochemicals (e.g., glucose) with this approach. A CAP membrane allows high enzyme loadings, and thus enables use of microminiature probes, and / or diagnosis of low levels of the analyte(s), with sufficient signal-to-noise ratio and low background current.

The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and / or detection of particles, such as cells and / or beads. The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and / or analysis of particles, such as cells, viruses, organelles, beads, and / or vesicles. The invention also provides microfluidic mechanisms for carrying out these manipulations and analyses. These mechanisms may enable controlled input, movement / positioning, retention / localization, treatment, measurement, release, and / or output of particles. Furthermore, these mechanisms may be combined in any suitable order and / or employed for any suitable number of times within a system. Accordingly, these combinations may allow particles to be sorted, cultured, mixed, treated, and / or assayed, among others, as single particles, mixed groups of particles, arrays of particles, heterogeneous particle sets, and / or homogeneous particle sets, among others, in series and / or in parallel. In addition, these combinations may enable microfluidic systems to be reused. Furthermore, these combinations may allow the response of particles to treatment to be measured on a shorter time scale than was previously possible. Therefore, systems of the invention may allow a broad range of cell and particle assays, such as drug screens, cell characterizations, research studies, and / or clinical analyses, among others, to be scaled down to microfluidic size. Such scaled-down assays may use less sample and reagent, may be less labor intensive, and / or may be more informative than comparable macrofluidic assays.

A porous β-tricalcium phosphate material for bone implantation is provided. The multiple pores in the porous TCP body are separate discrete voids and are not interconnected. The pore size diameter is in the range of 20-500 μm, preferably 50-125 μm. The porous β-TCP material provides a carrier matrix for bioactive agents and can form a moldable putty composition upon the addition of a binder. Preferably, the bioactive agent is encapsulated in a biodegradable agent. The invention provides a kit and an implant device comprising the porous β-TCP, and a bioactive agent and a binder. The invention also provides an implantable prosthetic device comprising a prosthetic implant having a surface region, a porous β-TCP material disposed on the surface region and optionally comprising at least a bioactive agent or a binder. Methods of producing the porous β-TCP material and inducing bone formation are also provided.

The present invention provides compositions and methods for light-activated cation channel proteins and their uses within cell membranes and subcellular regions. The invention provides for proteins, nucleic acids, vectors and methods for genetically targeted expression of light-activated cation channels to specific cells or defined cell populations. In particular the invention provides millisecond-timescale temporal control of cation channels using moderate light intensities in cells, cell lines, transgenic animals, and humans. The invention provides for optically generating electrical spikes in nerve cells and other excitable cells useful for driving neuronal networks, drug screening, and therapy.

The present invention provides an in vitro system for compartmentalization of molecular or cellular libraries and provides methods for selection and isolation of desired molecules or cells from the libraries. The library includes a plurality of distinct molecules or cells encapsulated within a water-in-oil-in-water emulsion. The emulsion includes a continuous external aqueous phase and a discontinuous dispersion of water-in-oil droplets. The internal aqueous phase of a plurality of such droplets comprises a specific molecule or cell that is within the plurality of distinct molecules or cells of the library.

Non-adhesive particles as large as 110 nm can diffuse rapidly in the brain ECS, if coated with hydrophilic coatings such as PEG coatings and preferably having neutral surface charge. The ability to achieve brain penetration with larger particles will significantly improve drug and gene delivery within the CNS since larger particles offer higher drug payload, improved drug loading efficiency, and significantly longer drug release durations.

The invention relates to a microfabricated device for the rapid detection of DNA, proteins or other molecules associated with a particular disease. The devices and methods of the invention can be used for the simultaneous diagnosis of multiple diseases by detecting molecules (e.g. amounts of molecules), such as polynucleotides (e.g., DNA) or proteins (e.g., antibodies), by measuring the signal of a detectable reporter associated with hybridized polynucleotides or antigen / antibody complex. In the microfabricated device according to the invention, detection of the presence of molecules (i.e., polynucleotides, proteins, or antigen / antibody complexes) are correlated to a hybridization signal from an optically-detectable (e.g. fluorescent) reporter associated with the bound molecules. These hybridization signals can be detected by any suitable means, for example optical, and can be stored for example in a computer as a representation of the presence of a particular gene. Hybridization probes can be immobilized on a substrate that forms part of or is exposed to a channel or channels of the device that form a closed loop, for circulation of sample to actively contact complementary probes. Universal chips according to the invention can be fabricated not only with DNA but also with other molecules such as RNA, proteins, peptide nucleic acid (PNA) and polyamide molecules.

The invention provides a method of sensitising target cells to ultrasound energy using a stimulus such as an electric field. This "electrosensitisation" enables target cells to be disrupted by ultrasound at frequencies and energies of ultrasound which do not cause disruption of non-sensitised (i.e., non-target) cells. As a consequence, the method increases the selectivity of ultrasound therapy, providing a way to ablate undesired cells, such as diseased cells (e.g., tumor cells) while minimising harm to neighboring cells. In another aspect, however, ultrasound can be used to sensitise cells while the electrical field is used to disrupt cells. The invention also provides an apparatus for performing the method and assays for identifying gene products and other molecules involved in apoptosis.

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.

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.

In accordance with the present invention, there are provided methods for the extension of serum half-lives of proteinaceous molecules, particularly antibody molecules, and compositions of molecules modified in accordance with the methods of the invention. In accordance with a first aspect of the present invention, there is provided a method of modifying the half-life of an antibody through providing an antibody containing an FcRn binding domain or the genes encoding such antibody and physically linking the antibody or the antibody as encoded to a second FcRn binding domain. In accordance with a second aspect of the present invention, there is provided a molecule that contains at least two distinct FcRn binding moieties.

The present invention is directed to a method for determining the effect of each of a plurality of test agents on cells from a subject, and a method to profile patient cell responses to test agents.

The invention features methods for separating cells from a sample (e.g., separating fetal red blood cells from maternal method begins with the introduction of a sample including cells into one or more microfluidic channels. In one embodiment, the device includes at least two processing steps. For example, a mixture of cells is introduced into a microfluidic channel that selectively allows the passage of a desired type of cell, and the population of cells enriched in the desired type is then introduced into a second microfluidic channel that allows the passage of the desired cell to produce a population of cells further enriched in the desired type. The selection of cells is based on a property of the cells in the mixture, for example, size, shape, deformability, surface characteristics (e.g., cell surface receptors or antigens and membrane permeability), or intracellular properties (e.g., expression of a particular enzyme).

The present invention provides compositions and methods for light-activated cation channel proteins and their uses within cell membranes and subcellular regions. The invention provides for proteins, nucleic acids, vectors and methods for genetically targeted expression of light-activated cation channels to specific cells or defined cell populations. In particular the invention provides millisecond-timescale temporal control of cation channels using moderate light intensities in cells, cell lines, transgenic animals, and humans. The invention provides for optically generating electrical spikes in nerve cells and other excitable cells useful for driving neuronal networks, drug screening, and therapy.