Abstract: A catalyst preparation comprising an insoluble matrix and an enzyme complex immobilized onto said insoluble matrix, characterized in that the matrix contains active carbon. The content of the active carbon is preferably in an amount of 0.1 to 70% by weight, more preferably 1 to 40% by weight and most preferably 3 to 20% by weight, relative to the entire matrix. The enzyme, particularly a lipase, is preferably coated with a surfactant. The inorganic insoluble matrix is preferably a silica-based matrix or an ion-exchange resin. The catalyst preparation of the invention is intended for use as a catalyst in esterification, inter-esterification and trans-esterification reactions.

Abstract: Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A biomolecule such as a glycoprotein having an unsubstituted amide moiety is combined with an amine forming agent to form an amine-functional biomolecule. The amine-functional biomolecule is combined with a medical device surface having a chemical moiety such as aldehyde, epoxide, isocyanate, 1,2-dicarbonyl, phosphate, sulphate or carboxylate to form a chemical bond immobilizing the biomolecule on the surface. The chemical bond may be combined with a reducing agent or a stabilizing agent. The aldehyde moiety may be formed by combining a periodate with a 2-aminoalcohol moiety or a 1,2-dihydroxy moiety. Alternatively, an amine-functional medical device surface is combined with a biomolecule having a chemical moiety that reacts with an amine moiety.

Abstract: In a method for immobilizing biomolecules and affinity ligands water insoluble matrices, having amino groups and selected from test tubes, microtiter plates, microscope slides, beads, membranes, resins, and filters, are reacted with a cyclobutene carboxylic acid derivative, such as cyclobutene carboxylic acid diester, cyclobutene carboxylic acid halide, cyclobutene carboxylic acid ester halide, cyclobutene carboxylic acid dialkoxyester, and cyclobutene carboxylic acid imidazole, as an activating compound in methanol and triethylamine to form active matrices with active groups. A protein containing at least one primary or secondary amino group, is dissolved and added to the matrices. The activated matrices and the dissolved protein are incubated at pH of 7-10 and a temperature of +4° C. to +60° C. in an aqueous buffer system, free of primary and secondary amines, to thereby immobilize the protein on the matrices.

Abstract: A sensor element is provided including a polymer exhibiting a measurable property from the group of luminescence and electrical conductivity, the polymer being complexed with a unit including a recognition element, a tethering element and a property-altering element bound thereto so as to alter the measurable property, the unit being susceptible of subsequent separation from the polymer upon exposure to an agent having an affinity for binding to the recognition element whereupon the separation of the unit from the polymer results in a detectable change in the measurable property.

Abstract: An electrochemical affinity assay system for detection of ligand—ligand receptor binding.

Abstract: A material comprising a biologically active substance (or ligand) to be sterilized, including proteins (e.g., antibodies and enzymes), peptides, DNA, RNA, and glycoproteins, with or without a carrier, and sterilization-protecting agent comprising a trisaccharide or higher saccharide (“polysaccharide”) having a positive charge, is provided. The skeletal background of the polysaccharide confers stability to the ligand and its positive charge traps destructive radicals produced during the sterilization process. The molecular weight ratio of sterilization-protecting agent to the ligand should be at least {fraction (1/500)} but less than ½ to protect the ligand effectively without obstructing the ligand's activity. In particular, polysaccharides, such as chitosan (a polymer of D-glucosamine) and chitin which is partially converted into chitosan, are preferable as a sterilization-protecting agent.

Abstract: This invention relates methods for conditioning affinity chromatography resins to decrease leaching of the ligand during purification. The methods involve incubating the resin in a buffered solution of a hydroxyalkylamine compound (e.g., ethanolamine) prior to use of the resin for an affinity purification. The treatment removes unstably bound ligand from the resin.

Abstract: Compounds are disclosed having the general formula R1-X-R2, wherein R1 and R2 are biologically active groups, at least one of which is polypeptidic. X is a non-peptidic polymeric group. R1 and R2 may be the same or different. Preferred R1 and R2 groups are TNF inhibitors.

Abstract: A microsphere is prepared containing a compound possessing physiological activity coupled to a styrene-glycidyl methacrylate polymer through a spacer. Compounds that may be used include receptors such as proteins, and 3-[(5-(2,3-dimethoxy-6-methyl-benzoquinonyl)]-2-nonyl-2-propionic acid. A preferred spacer is an ethylene glycol diglycidyl ether derivative. Preferably, the whole surface of the styrene-glycidyl methacrylate polymer is covered with glycidyl methacrylate. The microsphere may be used for isolating and detecting substances such as proteins that bind to the coupled compound.

Abstract: This invention relates to methods for the stabilization, storage and delivery of biologically active macromolecules, such as proteins, peptides and nucleic acids. In particular, this invention relates to protein or nucleic acid crystals, formulations and compositions comprising them. Methods are provided for the crystallization of proteins and nucleic acids and for the preparation of stabilized protein or nucleic acid crystals for use in dry or slurry formulations. The present invention is further directed to encapsulating proteins, glycoproteins, enzymes, antibodies, hormones and peptide crystals or crystal formulations into compositions for biological delivery to humans and animals. According to this invention, protein crystals or crystal formulations are encapsulated within a matrix comprising a polymeric carrier to form a composition.

Abstract: A method is provided for preparing an active slide, including introducing a monomer containing an aldehyde group, or a mixture of a monomer containing an aldehyde group and an acidic functional group provider into a plasma chamber; and depositing the aldehyde group and acidic functional group onto the surface of an organic or inorganic matrix using plasma deposition to form a slide comprising a layer of polymerized actively functional groups thereon. The aldehyde groups and negatively charged groups are deposited on the surface of the active slide, such that the bio-molecules bound thereto possess the properties of an inducible orientation and thus form a mono-layer.

Abstract: Molded articles formed of polystyrene or other polymers containing an aromatic moiety can be derivatized on the surface of the article by subjecting the molded article to a chemical reaction wherein the reaction media utilizes tetramethylsulfone as the reactant solvent and a suitable substituent group which is substituted on to the aromatic moiety of the polystyrene or other polymer by electrophilic substitution. By choosing the substituent group to further include a leaving group, further substitution of the primary substituent can be effected normally by nucleophilic substitution reaction. In this way, biologically important molecules can be attached to a polystyrene or other aromatic containing polymer without effecting certain properties of the molded article such as its optical or spectroscopic clarity.

Abstract: A polybifunctional reagent is provided having a polymeric backbone, one or more pendent latent reactive (preferably photoreactive) moieties, and two or more pendent bioactive groups. The reagent can be activated to form a bulk material or can be brought into contact with the surface of a previously formed biomaterial and activated to form a coating. The pendent bioactive groups function by promoting the attachment of specific molecules or cells to the bulk material or coated surface. Bioactive groups can include proteins, peptides, carbohydrates, nucleic acids and other molecules that are capable of binding noncovalently to specific and complimentary portions of molecules or cells.

Abstract: Biological materials in a mixture of substances are separated, detected or quantified using magnetic spherically shaped cross-linked polyvinyl alcohol (PVAL) polymer particles ranging in size from 1 to 10 &mgr;m. The particles containing a coupled ligand are used to bind a biological material in a mixture of substances, and the particles containing bound biological material are isolated from the mixture. The particles are prepared by dispersing a magnetic colloid containing a magnetic material such as a ferromagnetic or superparamagnetic substance in an aqueous solution of polyvinyl alcohol containing reactive hydroxyl groups, adding the resultant mixture to an organic phase containing a mixture of at least two emulsifiers, and adding a water-soluble cross-linking agent such as a dialdehyde that reacts with the hydroxyl groups of polyvinyl alcohol to form the polymer particles.

Abstract: Disclosed is a method for fabricating biosensors, using hydrophilic polyurethane. Bio-active reagents, including enzymes, antibodies, antigens, cells and receptors, are mixed with hydrophilic polyurethane and the mixture is directly coated over a signal transducer to form a sensing film which serves as a signal detector. The method using hydrophilic polyurethane allows the simplification of the fabrication of biosensors without conducting complicated chemical reactions and washing steps, such as crosslinking. The bio-active reagent entrapped within the hydrophilic polyurethane film can retains its high activity for an extended period of time and the intrinsic potentiometric response of the underlying ion-selective polymeric membrane is not affected by the bio-active reagent immobilized polyurethane film coated on its sensing surface. Therefore, the biosensors are superior in specificity, selectivity, and stability.

Abstract: The present invention relates to the field of carbohydrate crosslinked glycoprotein crystals. Advantageously, such crosslinked glycoprotein crystals display stability to harsh environmental conditions, while maintaining the structural and functional integrity of the glycoprotein backbone. According to one embodiment, this invention relates to methods for concentrating proteins that have been modified by carbohydrates and for releasing their activity at controlled rates. This invention also provides methods for producing carbohydrate crosslinked glycoprotein crystals and methods for using them in pharmaceutical formulations, vaccines, immunotherapeutics, personal care compositions, including cosmetics, veterinary pharmaceutical compositions and vaccines, foods, feeds, diagnostics, cleaning agents, including detergents and decontamination formulations.

Abstract: The invention includes a microsphere comprising styrene-glycidyl methacrylate polymer, and methods for isolation, purification and identification of receptors to a specific compound possessing physiological activity. In addition, the invention provides proteins isolated and purified using the microspheres of the invention.

Abstract: Reagents suitable for the modification of a bioactive species for the purpose of incorporating one or more phenyldiboronic acid (PDBA) moieties for subsequent conjugation to a different (or the same) bioactive species having one or more pendant boronic compound complexing moieties of the general formula of General Formula I, wherein group R is a reactive electrophilic or nucleophilic moiety suitable for reaction of the PDBA reagent with a bioactive species. Group Z is a spacer selected from a saturated or unsaturated chain up to about 0 to 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one intermediate amide or disulfide moiety, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length. Group Q is a linkage that includes one of amide, ether and thioether moieties.

Abstract: A tissue engineering scaffold for cell, tissue or organ growth comprises a biocompatible porous polyurethane cellular material comprising a plurality of substantially spherical voids of diameter from 20 to 300 microns, preferably 80 to 200 microns, interconnected by generally elliptically shaped pores. The cellular material has a void content of from 85% to 98% and a surface area to volume of from 5 to 400 mm2/mm3, ideally from 20 to 80 mm2/mm3.

Abstract: A test piece for use in biological analyses includes a plurality of different known specific binding substances disposed in predetermined positions on a substrate. The specific binding substances are disposed on a plurality of surfaces provided by the substrate and arranged in the direction of thickness of the substrate.

Abstract: A particle resistant to storage of at least one first and at least one second component, wherein said second component of at least one crosslinkable polymer as a shell at least partially envelops and/or encloses said first component as a core and said first component has at least one ascertainable property, obtainable by reacting said first component with the crosslinkable polymer and subsequently reacting the formed product with a crosslinking agent such that the first component with resistance to storage remains within the second component.

Abstract: The present invention is directed to a method for producing reversibly soluble, catalytically active enzyme-polymer conjugates and the products thereof. In particular, the invention is directed to reversibly soluble catalytically active enzyme-polymer conjugates made by incorporating enzymes modified to contain free vinyl double bonds into reversibly soluble polymers i.e., polymers that reversibly respond to slight changes in the environment, such as temperature, ionic strength, pH, electric fields, etc., during the polymerization reaction. Thus, when modified enzymes are incorporated into reversibly soluble polymers, the biocatalysts obtained can be precipitated without destroying the delicate enzyme(s). Moreover, these biocatalysts can be solubilized again and reused at the initial environmental conditions.

Abstract: Modifications of vitamin K-dependent polypeptides that lead to enhanced protein function on a weight or molar basis and/or increase of protein lifetime in the circulation are described. Both objectives are important for using vitamin K-dependent polypeptides for pro- and anti-coagulation therapies, as well as for other uses in the circulation.

Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.

Abstract: Modified enzymes are prepared for use in skin care products by covalently coupling to the enzymes from 4 to 70 polymeric molecules with or without a linker such as a triazine ring. Molecular weight of the polymeric molecules may be from 1 to 35 kDa and of the enzymes from 15 to 100 kDa. The number and weight of polymeric molecules coupled is balanced with the weight and/or surface area of the enzymes. Enzymes include proteases such as subtilisins, lipases and oxidoreductases such as laccases and superoxide dismutase, and polymeric molecules include polysaccharides such as dextran or pullulan and polyalkylene oxides such as polyethylene glycol. The polymeric molecules may be coupled to the enzymes at the N-terminal amino group and/or lysine residues, and preferably at a position more than 5 Å from the active site of the enzymes. A preferred modified enzyme is a protease having from 5 to 13 coupled polymeric molecules.

Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.

Abstract: Embodiments include reagents to modify a bioactive species for incorporating a bifunctional boronic compound complexing moiety for subsequent conjugation to a different or same bioactive species having pendant phenylboronic acid moieties of General Formula I, wherein group R is an electrophilic or nucleophilic moiety suitable for reaction of the putative bifunctional boronic compound complexing reagent with a bioactive species, wherein group R2 is selected from one of H and OH moieties, and wherein group R3 is selected from one of an alkyl and a methylene bearing an electronegative substituent. Group Z is a spacer selected from (CH2)n and CH2O(CH2CH2O)n2, wherein n is an integer of from 1 to 5, and wherein n2 is an integer of from 1 to 4. Group Z2 and Z3 is a spacer and need not be the same.

Abstract: The present invention is an improvement to the method of determining the concentration of an analyte in body fluid using at least two immunoreactants which specifically bind with separate epitopes of the analyte one of which immunoreactant is immobilized on a solid support and the other is in the form of a polymer or oligomer of the immunoreactant and an enzyme. The improvement involves introducing to the assay system a polymeric conjugate of the enzyme and a water soluble protein other than the enzyme or a non-proteinaceous natural, synthetic or semi-synthetic polymer or oligomer in sufficient amount to reduce bias in the assay due to incorrect recovery of the analyte.

Abstract: A particle resistant to storage of at least one first and at least one second component, wherein

Abstract: Azlactone-functional supports are used to provide cell selection from a mixture such as bone marrow or peripheral blood having a desired target cell population. An azlactone-functional support is derivatized by covalently coupling to the support a biologically active substance that binds the target cells. A mixture containing the target cells is contacted with the derivatized support to bind the target cells to the biologically active substance, and unbound remaining mixture is removed from the support. Bound cells may be eluted from the support to obtain purified target cells. Biologically active substances include antibodies, lectins, proteins, antigens and avidin. The biologically active substance may directly or indirectly bind cells in the mixture. Indirect binding may be through a second, intermediary biologically active substance that is bifunctional.

Abstract: The invention relates to a method of evaluating the immunological status of a subject comprising the steps of 1) determining the content of an antibody in a liquid sample from the subject using an immunoassay, wherein the reaction between the antibody of the sample and a ligand in the form of an antigen, an antibody or a hapten, the ligand being directed to the Fab region of the sample antibody, is carried out in the presence of other constituents of the sample to obtain a measurement 1, 2) determining the content of an antibody in the liquid sample using an immunoassay, wherein the reaction between the antibody of the sample and a ligand in the form of an antigen, an antibody or a hapten, the ligand being directed to the Fab region of the sample antibody, is carried out in the absence of other constituents of the sample to obtain a measurement 2, and 3) interrelating measurements 1 and 2 to express the interference and using the interference as a parameter for evaluating the immunological status of the subje

Abstract: A material comprising a to-be-sterilized material and a sterilization-protecting agent comprising a trisaccharide or higher saccharide having a positive charge(s).

Abstract: The present invention provides solid supports (e.g., glass) and polymer hydrogels (particularly polymer hydrogel arrays present on a solid support) comprising one or more reactive sites for the attachment of biomolecules, as well as biomolecules comprising one or more reactive sites for attachment to solid supports and polymer hydrogels. The invention further provides novel compositions and methods for the preparation of biomolecules, solid supports, and polymer hydrogels comprising reactive sites. The invention also provides for preparation of crosslinked solid supports, polymer hydrogels, and hydrogel arrays, wherein one or more biomolecules is attached by means of the reactive sites in a photocycloaddition reaction. Advantageously, according to the invention, crosslinking of the hydrogel and attachment of biomolecules can be done in a single step.

Abstract: Photocurable and photopatternable compositions are disclosed which comprise a) at least one copolymer derived from 1 to 99 parts by weight of at least one azlactone-functional monomer and 0 to 99 parts of at least one co-monomer; and b) at least one photocrosslinker. Articles are disclosed comprising a substrate and a gel layer of the cured composition which may be photopatterned with high resolution and used to bind biomolecules to the substrate.

Abstract: The present invention relates to the field of carbohydrate crosslinked glycoprotein crystals. Advantageously, such crosslinked glycoprotein crystals display stability to harsh environmental conditions, while maintaining the structural and functional integrity of the glycoprotein backbone. According to one embodiment, this invention relates to methods for concentrating proteins that have been modified by carbohydrates and for releasing their activity at controlled rates. This invention also provides methods for producing carbohydrate crosslinked glycoprotein crystals and methods for using them in pharmaceutical formulations, vaccines, immunotherapeutics, personal care compositions, including cosmetics, veterinary pharmaceutical compositions and vaccines, foods, feeds, diagnostics, cleaning agents, including detergents and decontamination formulations.

Abstract: The present invention is directed to a composition and method for regulating the adhesion of cells and biomolecules to hydrophobic surfaces and hydrophobic coated surfaces. The composition is a biomolecule conjugated end-group activated polymer (EGAP). The biomolecule conjugated EGAP can be put to numerous uses including cell adhesion, cell growth, cell sorting, and other biological assays.

Abstract: A method of preparing a polymer-protein composite based upon placing a protein in solution in an organic phase via the ion-pairing of the protein with a surfactant. The polymer-protein composites are useful, for example, as highly active and stable catalysts, in for example, paints and coatings, as well as in medical application.

Abstract: The present invention is directed to a composition and method for regulating the adhesion of cells and biomolecules to hydrophobic surfaces and hydrophobic coated surfaces. The composition is a biomolecule conjugated end-group activated polymer (FGAP). The biomolecule conjugated EGAP can be put to numerous uses including cell adhesion, cell growth, cell sorting, and other biological assays.

Abstract: An electrochemical affinity assay system for detection of ligand—ligand receptor binding.

Abstract: The invention relates to magnetic, spherical PVAL particles produced through suspension of a polymer phase containing magnetic colloids in a vegetable oil phase containing a special emulsifier mixture. Particles with a particle size of 1-8 &mgr;m are obtained which can chemically bind ligands. The carriers can be used to isolate and detect biomolecules, cells, antibodies and nucleic acids.

Abstract: An enzyme cleavable linker is prepared on which organic compounds are synthesized when the linker is bound to a solid phase. The linker contains a functional group on which a synthesized organic compound is bound when synthesis takes place, and a recognition site for a hydrolytic enzyme. Reacting the linker with the enzyme causes the linker to fragment at a site different from the recognition site to liberate the synthesized organic compound. The solid phase may be a crosslinked polyacrylamide containing an amino group for attaching the linker, and the linker is bound to the solid phase via a spacer. The spacer is attached to the solid phase by an ester, ether, amide or amine linkage, or a sulfide or phosphate linkage. In a specific reaction of forming a solid phase containing the linker, 2-acetoxy-5-hydroxymethylbenzoic acid is attached to an amino group-containing polymer via a spacer followed by conversion to a chloroformic ester.

Abstract: A method of attaching unmodified biopolymers, particularly, unmodified polynucleotides, directly to a solid support is provided. The method includes the steps of (a) providing unmodified biopolymers; (b) providing a solid support having at least one surface comprising pendant acyl fluoride functionalities, and (c) contacting the unmodified biopolymers with the solid support under a condition sufficient for allowing the attachment of the biopolymers to the solid support. The unmodified biopolymers may be nucleic acids, polypeptides, proteins, carbohydrates, lipids and analogues thereof. The unmodified polynucleotides may be DNA, RNA or synthesized oligonucleotides. The DNA may be single or double stranded. A device including a solid support and unmodified biopolymers attached to the solid support by reaction with the pendant acyl fluoride functionalities of the solid support is also provided. The methods and devices of the present invention may be used in performing hybridization assays and immunoassays.

Abstract: The present invention relates to the field of carbohydrate crosslinked glycoprotein crystals. Advantageously, such crosslinked glycoprotein crystals display stability to harsh environmental conditions, while maintaining the structural and functional integrity of the glycoprotein backbone. According to one embodiment, this invention relates to methods for concentrating proteins that have been modified by carbohydrates and for releasing their activity at controlled rates. This invention also provides methods for producing carbohydrate crosslinked glycoprotein crystals and methods for using them in pharmaceutical formulations, vaccines, immunotherapeutics, personal care compositions, including cosmetics, veterinary pharmaceutical compositions and vaccines, foods, feeds, diagnostics, cleaning agents, including detergents and decontamination formulations.

Abstract: A regenerated collagen fiber is subjected to water-insolubilizing treatment with a monofunctional epoxy compound to produce a water-insolubilized regenerated collagen fiber which can substantially maintain the color and the high knot tenacity, inherent in the collagen. Where the monofunctional epoxy compound is an epihalohydrin, a regenerated collagen fiber can be treated with this epihalohydrin and a sulfur compound to produce a water-insolubilized regenerated collagen fiber which can be permanent-wave set. In addition, the water-insolubilized regenerated collagen fiber can be converted into a fiber which can be permanent-wave set, by introducing a disulfide linkage into carboxylic groups of the collagen, which remain unmodified by the insolubilizing treatment.

Abstract: A size modified fibrinolytic enzyme, wherein the size of the enzyme is modified by covalent attachment of at least one large organic molecule to the enzyme.

Abstract: Spherically shaped polyvinyl alcohol (PVAL) polymer particles are prepared encapsulating a magnetic colloid that provides the particles with magnetic properties for use in binding biomolecules. The particles have a size of 1-10 &mgr;m that makes them particularly suitable for use in cell separation/sorting, cleaning biosubstances in suspension and diagnostic assays. The particles are prepared by dispersing a magnetic colloid containing a magnetic material such as a ferromagnetic or superparamagnetic substance in an aqueous solution of polyvinyl alcohol containing reactive hydroxyl groups, adding the resultant mixture to an organic phase containing a mixture of at least two emulsifiers, and adding a water-soluble cross-linking agent such as a dialdehyde that reacts with the hydroxyl groups of polyvinyl alcohol to form the polymer particles. The emulsifiers are miscible in the polyvinyl alcohol solution, and at least one emulsifier is semi-hydrophilic and at least one emulsifier is lipophilic.

Abstract: The invention pertains to an electrically conductive copolymer of the general formula I: wherein A is a first polymerizable monomer which produces an electrically conductive polymer when polymerized, and represents a polymerized unit of said monomer A in the electrically conductive polymer; B is a second polymerizable monomer which when copolymerized with monomer A produces an electrically conductive polymer, and represents a polymerized unit of said monomer B in the electrically conductive polymer; w is an integer greater than or equal to 0; x is an integer greater than or equal to 1; y is an integer greater than or equal to 0; z is an integer greater than or equal to I; 11, and 12 are each independently covalent linkers or spacer arms; 13 is substituent group having a desired chemical functionality; and Bt′ is selected from the group consisting of biotin and complexes of biotin with a molecule selected from the group consisting of avidin, streptavidin, derivatives of avidin

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 a method for detecting specific target-cells in a simple and time saving way, using paramagnetic particles, antibodies recognizing the Fc portions of target-cell associating antibodies and target-cell associating antibodies directed to specific antigen determinants in the target-cell membranes. Incubation of the cell suspension with a mild detergent and/or second set of antibodies or antibody fragments, prelabeled or not with fluorescent agents, metallocolloids, radioisotopes, biotincomplexes or certain enzymes allowing visualization, with dramatically increase the specificity of the method. The method can further be used for isolation of the target-cells by magnetic field application and kit for performing the method according to the invention is described.

Abstract: Collagen-containing tissue is cross-linked to provide tissue suitable for use in production of bioprosthetic devices. A cross-linking agent is used having an aliphatic component containing about 8 to 40 carbon atoms and two collagen-reactive groups such as isocyanate, epoxy or n-hydroxysuccinimide. The cross-linking agent may be produced by dimerizing fatty acids, and modifying carboxylic acid group of the fatty acids before or after dimerization to contain collagen-reactive groups. The cross-linked tissue has desirable mechanical and biocompatibility features and a reduced susceptibility to calcification.