W. R. Grace Co.-conn.

Large Scale Proteomics Corporation

US Government As Represented by the Secretary of the Army

Large Scale Biology Corporation

Hampshire Chemical Corp.

James A Braatz

Aaron H Heifetz

Clifton L Kehr

Norman G Anderson

Richard A Wolfe

N Leigh Anderson

Narender P Luthra

Timothy G Grasel

David M Donofrio

William S Letter

Denise A Miller

Gerald L Princler

Kenneth R McIntire

Microarrays are prepared by using a separate fiber for each compound being used in the microarray. The fibers are bundled and sectioned to form a thin microarray that may be glued to a backing.

Microarrays and their manufacture by slicing

Highly hydrophobic compounds and hydrophobic proteins are solubilized in a non-aqueous solvent containing an electrolyte for electrophoretic separation. The non-aqueous solvent is an ionic liquid or a mixture of an organic solvent containing an ionic liquid in an amount to render the solvent electrically conductive and amenable for electrophoretic separation. The hydrophobic proteins are separated by electrophoresis using an electrophoresis gel that is compatible with the organic solvent and ionic liquid.

Electrophoresis process using ionic liquids

Microarrays are prepared by using a separate fiber for each compound being used in the microarray. The fibers are bundled and sectioned to form a thin microarray that is glued to a backing.

Microarrays and their manufacture

A method is disclosed which relates to the placement of binding partners on microarrays, where such binding partners contain proteins, nucleic acids, biological cells and other bio-reactive components. The present invention discloses uses and methods for manufacture of microarrays constructed in part by sectioning bundles of tubules or rods containing matrix immobilized bio-reactive molecules to produce large numbers of sample chips. The chips so produced are processed by deposition to microarrays. The deposited chips can then be manipulated to partition the immobilizing matrix away from the bio-reactive molecules contained in the matrix and to place said partitioned molecules onto various surfaces for subsequent analysis, to include binding assays, hybridization reactions, diagnostic methods and a variety of cell interaction-determining methodologies.

Dry deposition of materials for microarrays using matrix displacement

Controlled release membranes are prepared from polyureaurethane polymer derived from prepolymer units at least 75% of which are oxyethylene-based diols or polyols having essentially all of the hydroxyl groups capped with polyisocyanate are disclosed. The membranes are characterized by their biocompatibility and resistance to nonspecific protein adsorption and are particuarly useful for delivery of proteinaceous materials in drug-delivery systems, i.e., wound dressings. Also disclosed are novel biocompatible, protein-nonadsorptive hydrated polymers and the method of producing the same.

Protein nonadsorptive membranes for wound dressings

The resistance to an oxidizer of a biocompatible polysulfone membrane can be enhanced by the incorporation of a specific hydrophilic polyurethane polymer.

Bleach resistant polysulfone/polyurethane composite membranes

Affinity matrices useful for the chromatography and immobilization of biological materials and the method of preparing and using the same are disclosed. The affinity supports are based on hydrated polyurethane polymers which have been activated to provide a means for covalently attaching a variety of bioaffinity agents. The hydrated polymer matrices are characterized by their biocompatibility and resistance to nonspecific protein adsorption. Preferably, the prepolymers used to prepare the hydrated polymers are isocyanate-capped oxyethylene-based diols or polyols, at least 75% of said diols and polyols having a molecular weight of 7000 to about 30,000.

Biocompatible, low protein adsorption affinity matrix

A class of hydrophilic prepolymers and hydrated polymer gels are disclosed which are characterized by their transparency, biocompatibility and resistance to nonspecific protein adsorption. At least 75%, preferably at least 90%, of the prepolymers are isocyanate-capped oxyethylene-based diols or polyols having molecular weight of about 7000-30,000. Essentially all of the hydroxyl groups of the diols or polyols are capped with polyisocyanate prior to formation of the hydrated polymer.

Biocompatible polyurea-urethane hydrated polymers

Polymer-coated medical and laboratory devices are disclosed which are characterized by their biocompatibility and resistance to nonspecific protein adsorption. The polyurea-polyurethane coatings of this invention are prepared from high molecular weight isocyanate end-capped prepolymers substantially or exclusively comprised of ethylene oxide units. At least 75%, preferably at least 90%, of the prepolymer units are oxyethylene-based diols or polyols having molecular weights of about 7000-30,000, with essentially all of the hydroxyl groups capped with polyisocyanate prior to formation of the hydrated polymer coating.

Protein non-adsorptive polyurea-urethane polymer coated devices

This nutrient medium is very effective for the serum-free or serum-protein-free culture of various animal cells, in both high and low density culture. Serum proteins have been replaced with non-protein-based cell growth enhancers and a non-serum derived protein supplement. The non-protein growth enhancer is a modified or derivatized polyurethane prepolymer of polymer and preferably is a sulfhydryl derivative of polyurethane. The protein supplement may be insulin, an insulin analog or an insulin-like growth factor.

Very low protein nutrient medium for cell culture

Biocompatible polymers derived from isocyanate-capped high molecular weight triols and higher polyols are covalently linked to drugs. These polymer-modified drugs have one or more of the following advantages over the unmodified drug: reduction of immunogenicity of the drug, increased circulating half-life of the drug due to longer residence time in circulation, ability to administer multiple drugs together, and enhanced potency of the drug.

Polymer-modified peptide drugs having enhanced biological and

A method of preparing a hydrophilic, biocompatible contact lens characterized by a surface which resists nonspecific protein adsorption. The method involves forming a prepolymer, at least 75% of which are oxyethylene-based diols and polyols having molecular weights of about 7000 to about 30,000. The prepolymer is subsequently gelled and hydrated to produce a hydrated polyurea-polyurethane polymer gel. The hydrated polymer gel is used to obtain a contact lens which resists nonspecific protein adsorption. Preferably, the contact lens are prepared by molding the prepolymer into a contact lens mold, prior to polymerization, to achieve the desired lens shape.

Method of making a hydrophilic, biocompatible, protein non-adsorptive

The cell culturing system of the present invention includes a tubular membrane, e.g. hollow fiber, cartridge. Provision is made for the continuous circulation of a nutrient-containing medium through the tube side of the cartridge by pumping the nutrient-containing medium in an endless loop. The cells to be cultured are placed within the cartridge on the shell side where the desired extracellular products are accumulated. Nutrients are assimilated into the cell culture through the semipermeable tubular membranes and waste products are removed by passing through the semipermeable membranes into the recirculating nutrient-containing medium. Within the endless loop are located a circulating pump, an oxygenator and a pH probe. The system additionally includes a variable delivery feed pump for continuously injecting fresh nutrient-containing solution into the loop, which feed pump is operated at a rate responsive to the measured pH. A portion of the stream exiting the cartridge is continuously split off at a rate identical to that for the introduction for fresh nutrient-containing solution in order to maintain cellular waste products at a suitably low level. The conventional nutrient-solution preparation reservoir has been eliminated from the loop in order to simplify the system and reduce the potential points of entry for contaminating microorganisms. The membrane cartridge is mounted with its longitudinal axis at approximately 60.degree. with respect to the horizontal.

Hollow fiber bioreactor culture system and method

A class of modified hydrophilic prepolymers and polymers is disclosed which are characterized by their specific reactivity. Isocyanate-capped oxyethylene-based prepolymers are modified by reacting with a compound having an isocyanate-reactive group which is a sulfhydryl group, an amino group, a hydroxyl group or a carboxyl group, and a non-isocyanate-reactive group, in quantities sufficient to modify at least a portion of the isocyanate groups of the prepolymer. Where said first functional group is an amino group contained in a diamine or polyamine compound or is a carboxyl group, the modifying compound is present in quantities sufficient to modify all or substantially all of the isocyanate groups of the prepolymer.

Chemically modified hydrophilic prepolymers and polymers

Modified hydrophilic prepolymers and polymers are disclosed wherein the prepolymers and polymers are characterized by cell growth enhancement, and, in some instances, antibody production stimulation. Isocyanate-capped oxyethylene-based prepolymers are modified by reaction with a compound having at least one isocyanate (NCO) reactive group. Preferably, the NCO reactive group is a sulfhydryl group, an amino group or a carboxyl group, in quantities sufficient to modify at least a portion of the isocyanate groups of the prepolymer. The prepolymer and polymer also express a free functional group, preferably an amino, sulfonic acid or a sulfhydryl. When the free functional group is sulfhydryl or sulfonic acid, antibody production stimulation, as well as cell growth enhancement, is observed.

Growing community of inventors

Beltsville, MD, United States of America

James A Braatz