Abstract: This invention provides polyanionic polymer conjugates containing non-nucleotide polyanionic polymers that are useful in detecting target analytes such as proteins or small molecules. The invention also provides nanoparticles bound to polyanionic polymer conjugates and methods of preparation and use thereof. The polyanionic polymer conjugates have the formula: L-O—[PO2—O-Z-O]n—PO2—O—X wherein n ranges from 1 to 200; L represents a moiety comprising a functional group for attaching the polyanion polymer to the nanoparticle surface; Z represents a bridging group, and X represents Q, X? or -Q-X?, wherein Q represents a functional group for attaching a recognition probe to the polyanion polymer, and X? represents a recognition probe.

Abstract: The present invention is directed to a method of patterning materials, such as proteins, on a contoured surface by depositing them onto protrusions on the surface and to a cell containment device that may be constructed by this method. In one embodiment, the present invention is directed to a method of selectively depositing a material on a substrate including a contoured surface including a protrusion and a recess. The method includes applying a first fluid to the contoured surface of the substrate and allowing the first fluid to distribute across a portion of the contoured surface such that the first fluid contacts the protrusion and not the recess. The method also includes allowing a first material to deposit on the substrate where the substrate is in contact with the first fluid.

Abstract: The invention relates to a macroporous plastics bead material with an average particle diameter from 10 to 1000 ?m, containing a copolymer of a) 5-60 wt. % vinylically polymerizable monomers with a water solubility of at least 1% at 20° C., b) 1-40 wt. % vinylically polymerizable monomers with an additional functional group, which can enter into covalent bonds with the nucleophilic groups of the ligands in a polymer-like reaction, c) 10-40 wt. % hydrophilic, crosslinking radical-polymerizable monomers with two or more ethylenically unsaturated polymerizable groups and d) 10-60 wt. % vinylically polymerizable monomers with a water solubility of at most 1% at 20° C. are contained, as a rule with the monomers a) to d) adding up to 100%.

Abstract: The instant invention provides a base material characterized by having a continuous three-dimensional honeycomb structure for regenerating an air sinus. The invention further provides methods for regenerating an air sinus using the base material. The base material has a composition and a structure that is similar to the wall and bone structure which allows it to becomes a scaffold of the regeneration of the mucosa tissue covering the surface of an air sinus.

Abstract: The invention provides for translating two-dimensional microfabrication technology into the third dimension. Two-dimensional templates are fabricated using high-resolution molding processes. These templates are then bonded to form three-dimensional scaffold structures with closed lumens. The scaffolds can serve as the template for cell adhesion and growth by cells that are added to the scaffolds through the vessels, holes or pores. These scaffolds can be formed by layering techniques, to interconnect flat template sheets to build up a fully vascularized organ.

Abstract: Semiconductor device-based chemical sensors and methods associated with the same are provided. The sensors include regions that can interact with chemical species being detected. The chemical species may, for example, be a component of a fluid (e.g., gas or liquid). The interaction between the chemical species and a region of the sensor causes a change in a measurable property (e.g., an electrical property) of the device. These changes may be related to the concentration of the chemical species in the medium being characterized.

Abstract: Methods and apparatus for bone implants that allow for the directed application of an osteogenic compound. The implant is preferably constructed of a biodegradable polymer formed into a structure having micro-architectural features and includes features that allow for in-situ application of a liquid biodegradable polymer to securely attach the implant to the surrounding tissue. The implant is constructed with a nozzle connected to a fluid supply that can be injected through a central channel and one or more distribution channels. The implant is designed so as to provide structural support to the damaged area. The implant and the fluid supply are preferably biodegradable polymers that contain an osteogenic material.

Abstract: The present invention provides compositions and methods for the separation of metals or molecules such as polypeptides, nucleic acids, or endotoxins using a metal-modified solid support. The metals or molecules are isolated from a starting material using the modified solid supports of the invention. Also provided by the invention are kits that can be used in connection with the inventive methods.

Abstract: A material includes a surface and a reactive agent that is located at the surface of the material, covalently attached to a backbone of the material, and/or located within the material. The reactive agent has nitrite reductase activity, nitrate reductase activity, and/or nitrosothiol reductase activity. The reactive agent also converts at least one of nitrites, nitrates and nitrosothiols to nitric oxide when in contact with blood. A reproducible nitrosothiol sensor is also disclosed.

Abstract: The invention relates to a novel method for enzymatic polymerization which includes (1) obtaining a reaction mixture including a monomer, a template, and an enzyme; and (2) incubating the reaction mixture for a time and under conditions sufficient for the monomer to align along the template and polymerize to form a polymer-template complex. The template can be a micelle, a borate-containing electrolyte, or lignin sulfonate. Such a complex possesses exceptional electrical and optical stability, water solubility, and processibility, and can be used in applications such as light-weight energy storage devices (e.g., rechargeable batteries), electrolytic capacitors, anti-static and anti-corrosive coatings for smart windows, and biological sensors.

Abstract: The present invention relates to medical devices that are to be implanted or inserted into the body of a patient for the purpose of removing undesired body tissues. In one embodiment of the invention the medical device comprises a body tissue removal agent for removing undesired body tissue simultaneously with or prior to treatment of body tissue that is in proximity to the undesired body tissue with a biologically active material. Such biologically active material may facilitate regeneration of the body tissue that was removed or may prevent the recurrence of the undesired body tissue.

Abstract: The invention is directed to a method for preparing an oxygen reduced film and package by inclusion of an oxygen scavenger coating that is activable upon exposure to water vapor during final package assembly. The film includes a composition having a non-aqueous liquid vehicle, a multicopper oxidase enzyme, an oxidizable substrate and an organic binder polymer, wherein the polymer is dissolved or dispersed in the liquid vehicle, wherein the enzyme and the substrate are in particulate form and dispersed in the liquid vehicle; and wherein the liquid vehicle is evaporated.

Abstract: The present invention is directed to arginine deiminase modified with polyethylene glycol, to methods of treating cancer, and to methods of treating and/or inhibiting metastasis.

Abstract: The invention relates to developments in the treatment of diabetes in mammals. Particularly it relates to a method of preparing a xenotransplantable porcine islet preparation capable upon xenotransplantation of producing porcine insulin in an appropriate recipient mammal, the method including or comprising the steps of: (I) harvesting the pancreas of piglets at or near full term gestation, and (ii) extracting pancreatic ? islet cells from the harvested pancreas wherein the islets (at least at some stage in the performance of the method) are exposed to nicotinamide. Further, the invention relates to a method of encapsulation of a xenotransplantable porcine islet preparation, and transplantation of such a preparation, or a capsule containing such a preparation, into an appropriate recipient mammal.

Abstract: Cell storage and delivery systems and methods for storing and delivering viable cells to a mammal are disclosed. The cell storage and delivery systems include a biodegradable and/or bioabsorbable fibrous matrix physically associated with viable cells to contain and release the cells at a controlled rate. The biodegradable and/or bioabsorable matrix can be formed by electrospinning fibers of biodegradable and/or bioabsorbable fiberizable material. The methods include methods for storing viable cells and for delivering viable cells to a mammal using the cell storage and delivery system.

Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.

Abstract: The invention relates to a novel method for enzymatic polymerization which includes (1) obtaining a reaction mixture including a monomer, a template, and an enzyme; and (2) incubating the reaction mixture for a time and under conditions sufficient for the monomer to align along the template and polymerize to form a polymer-template complex. The template can be a micelle, a borate-containing electrolyte, or lignin sulfonate. Such a complex possesses exceptional electrical and optical stability, water solubility, and processibility, and can be used in applications such as light-weight energy storage devices (e.g., rechargeable batteries), electrolytic capacitors, anti-static and anti-corrosive coatings for smart windows, and biological sensors.

Abstract: A porous solid ion exchange wafer having a combination of a biomolecule capture-resin and an ion-exchange resin forming a charged capture resin within said wafer. Also disclosed is a porous solid ion exchange wafer having a combination of a biomolecule capture-resin and an ion-exchange resin forming a charged capture resin within said wafer containing a biomolecule with a tag. A separate bioreactor is also disclosed incorporating the wafer described above.

Abstract: The present invention provides compositions for the separation of metals or biomolecules such as polypeptides, nucleic acids, or endotoxins using modified solid supports.

Abstract: The present invention provides compositions for the separation of metals or biomolecules such as polypeptides, nucleic acids, or endotoxins using modified solid supports.

Abstract: Disclosed are a method of adhering active enzymes to an inert support, the product produced thereby, and a method of using the enzyme-coated support in enzyme-catalyzed reactions such as the glucose isomerase-catalyzed conversion of glucose to fructose. The method includes the steps of coating an inert support with a cationic copolymer, preferably a polyamine, and most preferably a di-C1-C6-alkylamino-epichlorohydrin copolymer, and then adhering enzyme to the coated support in the absence of any intervening cross-linking agent.

Abstract: A method of patterning materials, such as proteins, on a contoured surface by depositing them onto protrusions on a surface, and a cell containment device that may be constructed by this method, are provided. The method may involve selectively depositing a material on a substrate including a contoured surface including protrusions and recesses. By applying a first fluid to the contoured surface and allowing the first fluid to distribute across only a portion of the contoured surface, a material may be deposited on the protrusions and not the recesses, or on the recesses and not the protrusions. Such a method may be used to selectively pattern cells or other materials on substrates.

Abstract: The present invention relates to an apparatus and methods that immobilize one or more cells associated with magnetic material on a substrate on which are located one or more magnetic receptacle(s). Alternatively, in another aspect the present invention, the device arrays cells associated with magnetic material on a substrate having a pattern of magnetic receptacles disposed thereon. The size of the magnetic receptacle(s) determines the number of target cells that it is capable of immobilizing. The size of the magnetic receptacle is defined by the strength of a localized magnetic field gradient. The localized magnetic field gradient may be derived from 1) permanent magnets embedded in the substrate or alternatively, the localized magnetic field gradient may be derived from an 2) external magnet whose strength is focused by objects of highly-permeable-magnetic material which create localized magnetic field gradients.

Abstract: In a preferred embodiment, a pipettor head, including: a body; one or more solenoid valves disposed in the body; each one or more solenoid valves having an outlet at a lower end and an inlet at an upper end; each one or more solenoid valves having an outlet attached to a dispensing passageway; each one or more solenoid valves having its inlet attached to a standpipe; and the standpipe having an open top communicating with an interior of a closed vacuum/pressure chamber defined in the pipettor head, the closed vacuum/pressure chamber being arranged such that vacuum or pressure may be selectively applied to the closed vacuum/pressure chamber. A method of using the pipettor head is also provided.

Abstract: A meat product containing in vitro produced animal cells in a three dimensional form and a method for producing the meat product.

Abstract: The present invention describes improved microfluidic systems and procedures for fabricating improved microfluidic systems, which contain one or more levels of microfluidic channels. The methods for fabrication the systems disclosed can provide a convenient route to topologically complex and improved microfluidic systems. The microfluidic systems can include three-dimensionally arrayed networks of fluid flow paths therein including channels that cross over or under other channels of the network without physical intersection at the points of cross over. The microfluidic networks can be fabricated via replica molding processes utilizing mold masters including surfaces having topological features formed by photolithography. The present invention also involves microfluidic systems and methods for fabricating complex patterns of materials, such as biological materials and cells, on surfaces utilizing the microfluidic systems.

Abstract: The present invention relates to a systematic process for the creation of functionally organized, spatially patterned assemblies polymer-microparticle composites including the AC electric field-mediated assembly of patterned, self supporting organic (polymeric) films and organic (polymeric)—microparticle composite films of tailored composition and morphology; the present invention further relates to the incorporation of said assemblies into other structures. The present invention. also relates to the application of such functional assemblies in materials science and biology. Additional areas of application include sensors, catalysts, membranes, micro-reactors, smart materials. Miniaturized format for generation of multifunctional thin films.

Abstract: Tissue engineered constructs including a matrix and cells transfected with a gene for a growth factor. The constructs may be implanted into a tissue site, where the growth factor gene enhances a metabolic function furthering integration of the construct in the tissue site. If the matrix is biodegradable, the metabolic result may include resorption of the matrix and replacement with tissue synthesized at least in part by the transfected cells.

Abstract: The present invention relates to the diagnosis of HIV infections. It especially teaches the production of a soluble retroviral surface glycoprotein-(or transmembrane glycoprotein)-chaperone complex and the advantageous use of a chaperone-antigen complex especially in the detection of antibodies to HIV in immunoassays, preferably according to the double antigen bridge concept, or as an immunogen. The invention also discloses soluble complexes comprising a variant of HIV-1 gp41 or a variant of HIV-2 gp36, respectively, and a chaperone selected from the peptidyl-prolyl-isomerase class of chaperones. Variants comprising specific amino-acid substitutions in the N-helical domain of HIV-1 gp41 or of HIV-2 gp36, respectively, are also described.

Abstract: Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided for use in numerous biomedical applications. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. PHAs are provided which are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone and other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses.

Abstract: Array systems that facilitate the simultaneous monitoring of many interactions between biological molecules and the analysis of cellular protein interactions with high throughput. The present invention provides methods and arrays for analyzing biochemical pathways by forming an array of immobilized biomolecules; exposing the array to biomolecules in solution; and detecting modification of the immobilized biomolecules, modification of the biomolecules in solution, and/or binding of biomolecules in solution to immobilized biomolecules.

Abstract: The present invention relates to a DNA polymerase immobilized by covalent bonding. More particularly, the present invention relates to an immobilized DNA polymerase whose activity is maximally preserved by masking the active site of the DNA polymerase and optimizing interaction of the masked molecule to the substrate material. In one embodiment, the average activity of the immobilized DNA polymerase is more than about 10% relative to that of the solution phase DNA polymerase. Further provided by the invention are methods and kits for performing polymerase chain reactions (PCR).

Abstract: The invention relates to a blood-compatible surface comprising a polymer surface and a plurality of conjugates made of linkers and active agents immobilized thereon. The polymer surface contains similar or different structural units that carry carbonyl groups. The linkers contain a structural element that is able to form a hydrogen bridge bond. A polyorganosiloxane acting as the active agent is linked to the linkers.

Abstract: Water soluble activated polymers are provided containing an active ethyl sulfone moiety having a reactive site located at the second carbon from the sulfone group. In an embodiment, a poly(ethylene glycol) (PEG) derivative is disclosed that is activated with the active ethyl sulfone moiety for selective attachment to thiol moieties on molecules and surfaces. The activated PEG is water soluble, hydrolytically stable for extended periods, and forms hydrolytically stable linkages with thiol moieties. The linkages generally are not reversible in reducing environments. The PEG derivative is useful for modifying the characteristics of substances including modifying biologically active molecules and surfaces for biocompatibility.

Abstract: The present invention is directed to methods of modulating viral replication in vivo comprising administering to an individual a therapeutically or prophylactically effective amount of a composition comprising arginine deiminase modified with polyethylene glycol, to methods of concurrently modulating viral replication and treating cancer, and to methods of modulating nitric oxide levels in a patient, among others.

Abstract: The present invention provides methods for determining a ratio of an amount of a glycated form of a protein to a total amount of the protein in a sample containing the glycated protein, the glycosylated protein, or the glycoprotein. The method incorporates lateral flow test strip or vertical flow test strip devices having negatively charged carboxyl or carboxylate groups and hydroxyboryl groups immobilized and interspersed on a solid support matrix. The solid support matrix may include derivatives of cellulose (e.g., carboxy cellulose) derivatized with carboxylic acid (e.g., carboxylate, carboxyl) groups and hydroxyboryl compounds including phenylboronic acid (e.g., phenylborate), aminophenylboronic acid, boric acid (e.g., borate), or other boronic acid (e.g., boronate) compounds. The present invention is usefi.il for monitoring glycation or glycosylation of hemoglobin or albumin for monitoring glycemic control (e.g., glycemia in diabetes).

Abstract: Provided are a nitrite-type nitrification carrier and a method for producing the same and a method and an apparatus for removing nitrogen using the same, in which the quantity of organic matter to be added can be substantially reduced to reduce running cost. A method for producing a nitrite-type nitrification carrier in which ammonia-oxidizing bacteria for nitrifying ammonium to nitrite is preferentially accumulated comprises the steps of: entrapping and immobilizing any sludge selected from sediment from a lake, a river or the sea, soil from the surface of the earth, or activated sludge from a sewage-treatment plant into a monomer or a prepolymer for immobilizing microorganisms; and then subjecting the entrapped and immobilized sludge to heat treatment at 30 to 80° C.

Abstract: A device and method are provided for isolating and culturing microorganisms from a bulk fluid sample. The device comprises a container having therein a polymeric immobilization layer having interstitial spaces between polymer chains such as a gel matrix. The interstitial spaces are of an average size less than an average size of microorganisms to be separated from the sample and cultured. A bulk fluid sample is applied to the immobilization layer where fluid is absorbed by the layer and microorganisms remain on the surface of the layer. After culturing, microorganism colonies are readily accessible on the surface of the layer for harvest and testing. The immobilization layer may contain one or more of nutrients for microorganisms growth, lytic agents, lytic enzymes, antibiotics, antibiotic neutralizers, indicators, detergents and selective agents. An adjacent support layer may be above and/or below the immobilization layer.

Abstract: A multilayer enzyme immobilization process is provided comprising adsorbing a polyethyleneimine (PEI) solution in a fibrous matrix, and adding an enzyme to the fibrous matrix, which comprises a plurality of fibrils. The process further comprises forming at least two layers of PEI-enzyme aggregates on the fibrils, and cross-linking the multilayer PEI-enzyme aggregates. The process can further comprise washing the fibrils containing the cross-linked PEI-enzyme aggregates with distilled water and acetic acid buffer subsequent to cross-linking. However, the PEI-containing matrix is not washed prior to the addition of enzyme. The enzyme can be ?-galactosidase and the fibrous matrix can be cotton cloth. The multilayer immobilized enzyme can be employed in a biocatalyst reactor for production of galacto-oligosaccharides from lactose and the hydrolysis of lactose to glucose and galactose.

Abstract: A process for the preparation of coated polymer particles containing superparamagnetic crystals, said process comprising reacting porous, surface-functionalized, superparamagnetic crystal-containing polymer particles of diameter 0.5 to 1.8 ?m with at least one polyisocyanate and at least one diol or at least one epoxide.

Abstract: Whole blood assays and kits are described for evaluating dosage of factor VIIa or activated protein C, as well as for monitoring responsiveness to factor VIIa or activated protein C.

Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.

Abstract: Biocompatible materials that have the ability to release nitric oxide (NO) in situ at the surface-blood interface when in contact with blood. The materials which may be polymers (e.g., polyurethane, poly(vinyl chloride), silicone rubbers), metals, such as stainless steel, carbon, and the like are provided with biocatalysts or biomimetic catalysts on their surface that have nitrite, nitrate, and/or nitrosothiol-reducing capability. Illustratively, the catalysts are adsorbed or immobilized at the surface of the material. The catalysts can act on endogenous nitrite, nitrate, or nitrosothiols within the blood creating a local increase in the NO levels at the surface of the material. An illustrative enzymatic biocatalyst is mammalian xanthine oxidase. In another illustrative embodiment, a biomimetic catalyst is a copper (Cu(II)-ligand complex, e.g. dibenzo[e,k]-2,3,8,9-tetraphenyl-1,4,7,10-tetraaza-cyclododeca-1,3,7,9-tetraene. In some cases, lipophilic salts of nitrite/nitrate (e.g.

Abstract: A selective adsorption material made by the process comprising: a) non-cavalently or reversibly-covalently binding a print molecule to at least two styrene, acrylate or silica monomers, each of which monomers brinds to said print molecule by means of a different functional group; b) immobilizing said bound monomers by being polymerized to each other in the presence of an effective amount of cross-linker; and c) removing said print molecule from said polymer by extraction to leave a cavity in said polymer which is stereo-tailored to a biological molecule of interest; and wherein said print molecule is the biological molecule of interest.

Abstract: A method for making a medical device having at least one biomolecule immobilized on a substrate surface is provided. One method of the present invention includes immobilizing a biomolecule comprising an unsubstituted amide moiety on a biomaterial surface. Another method of the present invention includes immobilizing a biomolecule on a biomaterial surface comprising an unsubstituted amide moiety. Still another method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties immobilized on medical device surfaces. Additionally, one method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties in solution, thereby forming a crosslinked biomaterial or a crosslinked medical device coating.

Abstract: The present invention utilizes the pre-sporulation (preconidial) mycelial stage of entomopathogenic fungi as insect attractants and/or pathogens. The fungus can be cultivated on grain, wood, agricultural wastes or other cellulosic material, attracting the insect and optionally introducing insect-specific pathogenic fungi. More than one fungus and substrate can be used in combination. The matrix of preconidial fungi can optionally be dried, freeze-dried, cooled and/or pelletized and packaged and reactivated for use as an effective insect attractant and/or biopesticide. Attractant extracts of the preconidial entomopathogenic mycelium are disclosed.

Abstract: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Abstract: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Abstract: The invention provides methods and compositions for the detection of Ehrlichia canis and Ehrlichia chaffeensis antibodies and antibody fragments.

Abstract: A composition containing polydisperse aminodextran polymer molecules is soluble in an aqueous solution at a concentration of 10 mg/ml. The molecules therein have a narrow size distribution characterized by an average molecule mean hydrodynamic diameter of greater than 115 nm, a polydispersity index of between 0.10 and 0.47, an average molecular weight (MW) greater than 3 million daltons, and an amine content of greater than 50 amines per molecule. Similar soluble compositions contain the polymer molecules with an average MW of greater than 7 million daltons. These compositions are useful in forming reagents by conjugation with proteins for labeling cells. Methods of making these compositions and reagents from conventional mixtures of aminodextran polymers involve fractionation on column chromatography.