Abstract: Spherical biocatalyst particles having increased abrasion resistance are obtained containing a biologically active material such as a microorganism, TiO.sub.2 particles having a size of 0.1 to 1 micrometer and an ionotropic biopolymer such as alginate, pectin, carrageenan or chitosan. The biocatalyst is prepared by forming a homogeneous degassed aqueous dispersion containing the biopolymer, 0.1 to 20% by weight of the biologically active material and 7 to 35% by weight of the TiO.sub.2 particles, and dropping droplets of the dispersion from a nozzle into a precipitation both containing polyvalent cations to precipitate the biopolymer and form spherical biocatalyst particles of 0.05 to 5 mm in diameter. The droplets may pass through a gas space containing an inert gas, air or reactive vapors such as acetaldehyde before reaching the precipitation bath. The TiO.sub.2 particles may be surface-impregnated with Al.sub.2 O.sub.3 and/or aluminum oxide hydrate.

Abstract: Particles which enclose cavities can be produced by adding a water-insoluble solid, liquid or gaseous cavity generating compound to an aqueous solution of a matrix material. Subsequent to forming particles by dispersion in a water-insoluble dispersion medium, the matrix is rendered insoluble in water by cooling, by covalent cross-linking or by polymerization. The cavity generating compound is washed out, whereafter the particles can be used as ion exchangers in gel filtration processes, in hydrophobic chromatography or in affinity chromatography, optionally subsequent to derivatizing the particles. The particles can also be used to advantage as microcarriers in the cultivation of anchorage dependent cells.

Abstract: The present invention provides a process for building an immobilized structure comprising multiple monolayers of effective sequential polymeric linkages. The multiple monolayers are built, monolayer by monolayer, from the surface of a solid phase, by an alternating reaction sequence conducted with multifunctional reagents. The process provides the capability of building numerous immobilized multiple monolayer structures wherein the length of each structure extending from a solid phase is substantially the same. Structures comprising multiple monolayers of polymeric linkages are useful for many purposes, as for example, immobilizing macromolecules or other biomolecules and the like to produce chemical or biochemical sensors. Other uses extend to molecular electronic applications, such as the production of molecular conductive wires and molecular circuitry.

Abstract: Biological cells are immobilized by forming a mixture of the cells and a first and second gel component, gelling the mixture with a gelling reagent and removing at least a portion of the first component to leave a gel containing the second component and the cells. Preferably, the first and second gel components are alignate and agarose, respectively, and the gelling reagent is calcium chloride.

Abstract: A method for sustained release of molecules from gels or microcapsules has been developed. The method is based on controlling the gel state using chelating agents or ion transfer. The method is particularly useful for controlling the rate of release of insolubilized proteins into physiological solutions.

Abstract: Enzymatic catalysts are produced from mineral particles coated with chitosan. The enzymes may be directly absorbed onto the surface after a cross-linking treatment to stablize the coating or immobilized by chemical bonds after a treatment with a bifunctional reagent, for example with glutaraldehyde. The stability of the biocatalyst is advantageously increased by retreatment with a bifunctional reagent after immobilization of the enzyme. Enzymes sensitive to glutaraldehyde are fixed by a carbodiimide. The catalysts thus prepared are insoluble in aqueous solutions. The particles are rigid and incompressible and are suitable for use in fixed-bed and fluidized-bed reactors. The immobilization yield may reach 90% depending on the circumstances.

Abstract: A water-soluble peroxidase derivative obtainable by the oxidation of peroxidase with periodic acid or with a salt thereof and binding to a water-soluble polymer selected from polysaccharides, polyethylene glycols, polyvinylpyrrolidones and polyacid anhydrides. Also provided is a process for the preparation of this water-soluble peroxidase derivative and for the use of this water-soluble peroxidase derivative for the determination of hydrogen peroxide.

Abstract: A cell culture microcarrier having positively charged cross-linked polysaccharides and basic groups linked therewith wherein the basic groups have the formula (I) ##STR1## with Z being an optionally substituted hydrocarbon chain having at least 2 carbon atoms,R.sub.1 and R.sub.2 being the same or different and representing alkyl, aryl, or aralkyl groups, andn is at least 1.

Abstract: A transplantable artificial tissue matrix structure containing viable cells which is suitable for insertion into the body is made by polymerizing precursors in an aqueous solution to form a shape retaining solid matrix comprising viable cells, matrix polymer and reversible gel polymer. The solution contains a matrix polymer precursor, a reversible gel polymer precursor, and viable cells. The reversible gel polymer is dissolved and removed to yield an insoluble, porous matrix containing viable cells. The conditions and reagents are selected to maintain the viability of the cells. The invention is particularly suitable for artificial transplant matrix tissue containing pancreatic islet cells.

Abstract: Sensitive proteins and other macromolecules, such as enzymes, antibodies, antigens, serum complement, fluorescent proteins, vaccine components, polysaccharides such as agarose etc, can be preserved by drying at ambient temperature and at atmospheric pressure in the presence of trehalose. A porous matrix impregnated with trehalose is provided as a receiver for a blood or other liquid sample to be dried.

Abstract: An immobilized enzyme having high activity and stability is obtained by immobilizing an enzyme on a water-insoluble amino group-containing carrier by use of a polyfunctional cross-linking agent such as glutaraldehyde in the presence of a phenolic carboxylic acid having one or more hydroxyl groups such as tannic acid. In addition to the phenolic carboxylic acid, a basic polysaccharide such as chitosan may also be present. The amino group-containing carrier may be aminated silica gel, aminated porous glass, aminated zeolite, or water insoluble crosslinked chitosen.

Abstract: Thiol gels are prepared from hydroxyl containing polymers by forming a 2-fluoro-1-methylpyridoxy derivative of the polymer followed by reacting the derivative with sodium dimethyldithiocarbamate and reducing to produce a sulfhydryl substituted polymer. Alternatively, the derivative is reacted with dithiothreitol to produce a sulfhydryl substituted polymer having free sulfhydryl groups spaced from the polymer. The thiol gel can be activated by means of 2,2'-dipyridyl disulfide and reacted with a free sulfhydryl containing biologically active ligand in order to provide an insolubilized ligand which can be used for various purposes including use as an immobilized biologically active material or use as a matrix in covalent chromatography.

Abstract: A method for protecting food systems from gram-positive bacterial spoilage by incorporating a bacteriocin is described. Foods incorporating the bacteriocin are described, particularly salads and salad dressings.

Abstract: The invention relates to compositions which are capable of selectively binding a biologically active protein, retaining its activity. Such compositions have essentially three parts, linked together: a water-insoluble carrier, an antibody bound by the carrier and being against the Fc region of an immunoglobulin and an antibody bound thereto which is specific towards the protein which is to be bound to this composition. Proteins of choice are enzymes and isoenzymes such as carboxypeptidas A or isoenzyme 5 of porcine lactate dehydrogenase. Preferably the antibody bound to the carrier is a polyclonal anti-mouse antibody and the antibody bound thereto is a monoclonal mouse antibody. Based on such compositions, there is provided an assay for the quantitative determination of such proteins.

Abstract: A process for the continuous production of cyclodextrins employs as a feedstock an aqueous solution of partially hydrolyzed starch with a dextrose equivalent between about 10 and about 15 as the feedstock for an immobilized cyclodextrin glycosyltransferase. In one variant the feedstock is sent to a membrane which removes cyclodextrins and glucose and the retentate is recycled to an immobilized glycosyltransferase so as to effectively utilize the feedstock. In another variant the effluent is passed through a water immiscibled liquid organic compound which forms a solid insoluble complex with cyclodextrins, the solids are continually removed, and the aqueous phase is recycled to an immobilized cyclodextrin glycosyltransferase as in the prior variant.

Abstract: This invention relates to novel microorganisms separated from natural environments and purified and genetically modified, process for immobilizing these microorganisms by affixing then to substrates, the biocatalytic compositions formed by these microorganisms affixed to substrates, and the use of the biocatalytic compositions for the detoxification of toxin-polluted streams. The microorganisms are (1) Pseudomonas fluorescens (ATCC SD 904); (2) Pseudomonas fluorescens (ATCC SD 903); (3) Pseudomonas cepacia (ATCC SD 905); (4) Methylobacter rhodinum (ATCC 113-X); and (5) Methylobacter species (ATCC 16 138-X).

Abstract: Biological control agents such as pathogenic bacteria and viruses have been encapsulated in a protective, starch matrix without the use of chemical crosslinking agents. The agent is blended into a dispersion of pregelatinized starch, which is thereafter subjected to conditions suitable for retrogradation. Dispersions can be formulated either for recovery of dry granules or as sprayable liquids. Encapsulated products are useful in controlling insects and other pest species having chewing mouth parts and amylase digestive enzymes.

Abstract: The present invention relates to a continuous process for the enzymatic preparation of isomaltulose. A periplasmatic sucrose-mutase is produced by fermentation of microorganisms which form sucrose-mutase. The cell-free crude enzyme extract is prepared by digestion of the cells and by cross-flow microfiltration. In a single-stage, simultaneous purification and immobilization of the sucrose-mutase from the cell-free crude extract conditioned by diafiltration is obtained by selective bonding to an anionizable carrier matrix. Direct conversion of sucrose into isomaltulose is produced by the sucrose-mutase bonded to the anionizable carrier matrix, preferably in cartridge or cartouche form.

Abstract: A method and apparatus for the separation of cells, organelles or proteins from a suspension or solution thereof, including:(a) coating ferromagnetic beads with an adsorption layer comprising antibodies, haptenes or chemical substrate adapted for binding the cells, organelles or proteins to be separated;(b) introducing said beads to a separation chamber having an entrance port and an exit port, the ratio of total volume of said beads to the chamber volume being of between 0.01 and 0.5, said chamber having magnetic field gradients in the regions of said entrance and exit ports to prevent the beads from leaving the chamber through the entrance or exit ports; and(c) passing the suspension or solution containing said cells, organelles or proteins into the entrance port through the chamber and out of the exit port to effect adsorption of the cells, organelles or proteins on said adsorption layer of the beads.

Abstract: Immobilized enzyme-polysaccharide graft copolymer products are prepared by hydrolyzing a polysaccharide graft copolymer and then contacting the hydrolyzed copolymer with an enzyme to immobilize the enzyme on the copolymer. The copolymer-enzyme products retain large quantities of active enzyme, and activity of the enzyme is retained over long periods of use. In the case of glucoamylase immobilized in accordance with the method of the invention, improved yield of glucose from starch is obtained.

Abstract: Gel beads of microbial cells or enzymes enclosed in gels are produced by forming a surface liquid stream of a gelling agent flowing from the center toward the peripheral wall of a vessel containing the gelling agent by a lower rotor on the liquid surface of the gelling agent, and dispersing a colloidal suspension of microbial cells or enzymes into a droplets by an upper rotor and allowing the dispersed droplets to fall onto the surface liquid stream, thereby contacting the droplets with the gelling agent. The lower and upper rotors may have vanes radially provided at a periphery of a lower and upper sides, respectively. In place of separate rotors, a single rotor may be used with lower and upper surfaces which respectively provide the functions of the lower and upper rotors. The lower and upper surfaces may also have radially provided vanes.

Abstract: A cell culture microcarrier having positively charged cross-inked polysaccharides and basic groups linked therewith wherein the basic groups have the formula (I) ##STR1## with Z being an optionally substituted hydrocarbon chain having at least 2 carbon atoms,R.sub.1 and R.sub.2 being the same or different and representing alkyl, aryl, or aralkyl groups, andn is at least 1.

Abstract: Providing a water slurry containing an immobilizing agent and an insoluble substance, such as calcium citrate, effective to cause gelation of the immobilizing agent. The water slurry is then contacted with a hydrophobic liquid, such as a vegetable oil under conditions leading to the formation of a dispersion of droplets of the water slurry in the hydrophobic liquid. The droplets gel to form microspheres by adding an oil-soluble organic acid, such as acetic acid to the dispersion containing the droplets. Possibility of producing microspheres which are very small and are constituted of nearly perfect spheres. If desired the method can be adapted to produce microspheres containing immobilized material.

Abstract: Encapsulated bodies are produced by bringing a fluid, which is to form the cores of the encapsulated bodies, and a solution, which has ability to form gel skins upon contact with the fluid, into contact and including a gelling reaction therebetween. A desired liquid, which is suitable for the utilization of the encapsulated bodies, is introduced successively into the reaction mixture in which the encapsulated bodies formed by the gelling reaction are dispersed. The liquid portion of the reaction mixture is hence substituted with the desired liquid and the resultant encapsulated bodies are therefore recovered in a form dispersed in the desired liquid. An apparatus suitable for use in the practice of the encapsulation is also disclosed.

Abstract: Acetic, propionic, and butyric acids are produced by a two-step fermentation process. Lactate salts formed in the second fermentation step, a biochemical acidification step, are used as the carbon source in the first fermentation step.

Abstract: Disclosed is a process for damage-free encapsulation of a variety of core materials including viable cells. The core material is suspended in an aqueous solution of a polymeric material containing cationic groups such as an aminated glucopolysaccharide, e.g. chitosan. A temporary matrix is formed by gelling droplets of the suspension with a divalent or multivalent anion. The temporary matrix is permanently cross-linked with a polymeric material containing plural anionic groups, e.g., polyaspartic or polyglutamic acid, to form a semipermeable membrane. The interior of the microcapsule may be resolublized by subjecting the capsule to a solution of low molecular weight cations. The process produces microcapsules which are not sticky, do not clump and allow viable cell growth and proliferation.

Abstract: Enzyme-containing granules are produced by forming drops of a gellable enzyme-containing liquid with a rotating disc and bringing the drops in contact with a gelling solution. The disc is preferably contained in a column, and the gelling solution flows down walls of the column to a reservoir in a lower legion of the column. Drops of the enzyme-containing liquid from the rotating disc contact the gelling solution while flowing down the walls and are carried to the reservoir. Preferably, the enzyme-containing liquid is an aqueous alginate solution containing the enzyme and the gelling solution is an aqueous calcium chloride solution.

Abstract: Living cells are encapsulated by: (a) dispersing living cells in an aqueous solution of a capsule wall-forming protein; (b) forming aqueous droplets of the cell containing dispersion in an aqueous-immiscible, cell compatible continuous processing medium; and (c) crosslinking the protein with a crosslinking agent which is soluble in the continuous processing medium but substantially insoluble in the aqueous droplets. The resultant capsules containing living cells may be treated with a capsule wall degrading enzyme to enlarge pores of the capsules. The encapsulated cells may be used for administration of cells to an animal for growing the cells in the animal or for delivery to the animal of a substance produced by the cells. By the cells being encapsulated, the cells are not destroyed by the aminal immune system and immune response by the animal may be minimized.

Abstract: A microorganism or enzyme is mixed with an alginate and a silica sol in the presence of water to obtain a liquid mixture having a pH of 3 to 10 and containing an alginate concentration of 0.5 to 3.5% (w/v) and a silica concentration originating from the silica sol of 0.5 to 35% (w/v). The mixture is contacted with a gelling agent in the form of an aqueous solution to obtain a gel containing the microorganism or enzyme.

Abstract: Microorganisms such as in activated sludge are immobilized by forming a mixture containing the microorganisms, a monomer or prepolymer and alginic acid or water soluble alignate, and dropping the mixture into a water solution of polyvalent metal ion and a polymerization initiator to form particles containing the microorganisms. Preferably, the monomer is an acrylamide monomer, the prepolymer is an ester of an acrylic acid group and polyethylene glycol and the polymerization initiator is a persultate. By this method, the microorganisms are protected from toxic substances such as the polymerization initiator during immobilization.

Abstract: Perfectly spherical, smooth and uniform microcapsules, which may contain living cells, are produced having a diameter less than 700 .mu.m, e.g. 150 to about 500 microns, by employing an electrostatic droplet generator. A droplet is suspended from a pointed source, such as a needle, and is charged with high static voltage. A collecting vessel or ring device is charged with opposing polarity and attracts the droplet When a voltage potential threshold is passed, the droplet moves from the source to the collecting vessel. The voltage pulse height, pulse frequency and length, and extrusion rate of the droplet are adjustable so that predetermined sizes of droplets may be repeatedly generated and collected.

Abstract: A mixture of a cyclodextrin and an alkoxy silane compound, e.g., tetraethoxy silane, is admixed with water and an acidic or alkaline catalyst, e.g., acetic acid, to effect ligand exchange and hydrolysis of the alkoxy silane followed by gelation into a gelled mass which is dried and, preferably, leached with water to remove excess of the cyclodextrin. The thus obtained gelled material is a composite having a structure in which the cyclodextrin molecules are incorporated into the matrix of amorphous silica presumably by forming Si-O-C linkages. The composite has characteristics as a combination of the properties of both of the component materials and can expand the applicability of the materials, for example, as a carrier of catalysts and immobilized enzymes, absorbent and adsorbent and so on.

Abstract: A fibrinolytic enzyme immobilized on a carrier is stabilized by treating the surface of the carrier on which the enzyme is immobilized with a basic amino acid. The amino acid is preferably histidine, arginine or lysine. Carriers may be inorganic materials, natural polymeric materials or synthetic polymeric materials, in a variety of forms. Fibrinolytic enzymes immobilized include plasmin, brinase, urokinase, streptokinase and tissue plasminogen activator. The stabilized immobilized fibrinolytic enzyme maintains activity better during storage or sterilization.

Abstract: An enzyme producing microorganism or an enzyme produced thereby is immobilized by contacting the microorganism or enzyme with polyethylenimine and adding chitosan and glutaraldehyde to form a reaction product. In a preferred embodiment, the reaction product is extruded onto the revolving plate of a spheronizing device to form spherical enzyme aggregates having enhanced physical and biocatalytic properties.

Abstract: Inocula having a long storage life and improved resistance to temperature and rehydration and a method of preparing them are disclosed. The method of the invention comprises admixing a culture medium containing microorganisms of the genus Rhizobium and at least one carbohydrate source in a polymer gel and then lowering the water activity of the resulting inoculum and maintaining the water activity at less than 0.1.

Abstract: A matrix useful for immobilizing organic ligands, such as biologically active materials, is prepared by reacting a hydroxyl group containing polymer with polyethyleneimine.

Abstract: The invention relates to a test strip for taking of daily blood sugar profiles, and also for glucose determination in urine for determining the individual kidney threshold of a diabetic as a daily profile, which finds use in glucose diagnosis.The objective of the invention is to stabilize the test strip in its function and to adapt it to customary measuring instruments, and this is achieved by attaching a film reaction membrane to a carrier, wherein the membrane was post treated with a complexing agent and an acyclic hydroxyamine or amino derivative.

Abstract: Adsorbents, which are suitable for the affinity chromatography of proteins, especially of interferons, and which consist of an electroneutral carrier matrix, --O--CH.sub.2 --CH(OH)--CH.sub.2 --NH- groups as the spacer and a triazine coloring substance bonded to the spacer.

Abstract: A naturally occurring protein is chemically modified to provide the protein with activity of a selected enzyme. The protein does not contain activity of the selected enzyme before modification. Modification is carried out by partially denaturing the protein, contacting the partially denatured protein with an immobilized enzyme inhibitor of the selected enzyme, crosslinking the protein in the presence of the inhibitor and recovering a modified protein having activity of the selected enzyme.

Abstract: The present invention relates to vaccine compositions which comprise at least one antigen chemically linked to a water-insoluble support combined with a pharmaceutically acceptable carrier. It also relates to a method of stimulating an organism's immune system by administration of these vaccine compositions.

Abstract: The invention relates to pharmaceutical compositions for use in the therapy of pathological states related to disturbances of the nervous stimulus in the central (CNS) and peripheral (PNS) nervous system containing as an active substance the cytidine monophosphate of 5-acetamido-3,5-dideoxy-D-glycero-D-galactononulosaminic acid. Moreover the invention relates to an improved method for preparing said compound by the condensation of cytidine triphosphate (CTP) with N-acetylneuraminic acid (NANA), catalyzed by the enzyme CMP-transferase (CMP-acylneuraminate synthase) (EC 2.7.7.43).

Abstract: The adsorbent consists of a solid phase, completely or partially penetrated by or surface-coated with a hydrophilic molecular polymer netting to which has been bound substituents or cross bridges having chain sequences of the structureX--CH.sub.2 --CH.sub.2 --SO.sub.2 --CH.sub.2 --CH.sub.2 --S--Ywhere X is ether oxygen, a thioether sulfur atom or a nitrogen atom and Y is a substituted or unsubstituted alkyl, aryl or heteroaromatic group. The solid phase consists of particles with a diameter of less than 1 mm and the molecular polymer netting consisting of a cross-linked polyhydroxy polymer such as a polysaccharide, preferably a polygalactane such as agar or agarose or a cross-linked polyamide, e.g. polyacryl amide. Y can be hydroxy alkyl or mercapto alkyl, or phenyl alkyl or phenyl substituted with halogen or nitro groups. The adsorbent is prepared by first converting in a known manner a hydrophilic polymer containing OH and/or CONH.sub.

Abstract: Living tissue or cells, for example, islets of Langerhans, are microencapsulated for implantation in the body for long term treatment of diabetes or other disease requiring organ transplantation. The microcapsules take the form of a biocompatible semi-permeable hydrogel membrane which permits the passage of materials and oxygen to the cells and metabolic products from the cells while retaining the cells encapsulated. The biocompatible semi-permeable membrane has an outer negatively-charged surface, which imparts to the microcapsules the ability to maintain long term effectiveness.

Abstract: Living tissue or cells, for example, islets of Langerhans, are microencapsulated for implantation in the body for long term treatment of diabetes or other disease requiring organ transplantation. The microcapsules take the form of a biocompatible semi-permeable hydrogel membrane based on polylysine which permits the passage of materials and oxygen to the cells and metabolic products from the cells while retaining the cells encapsulated. The biocompatible semi-permeable membrane has an outer negatively-charged surface, which, combined with a controlled thickness of polylysine of molecular weight from 10,000 to 30,000 daltons, imparts to the microcapsules the ability to maintain long term effectiveness.

Abstract: Isomaltulose is produced by a process in which at least the isomaltulose-forming enzyme system of an isomaltulose-forming micro-organism is immobilized and then the immobilized enzyme system is contacted with a sucrose solution to convert at least part of the sucrose to isomaltulose.

Abstract: A core material such as viable cells is encapsulated by gelling an alginate polymer with a polyvalent cation to form shape-retaining gelled masses containing the core material, expanding and hydrating the gelled masses by contacting the masses with an aqueous saline solution, and forming a membrane about the expanded gelled massed to form capsules by contacting the gelled masses with a polycationic polymer having a molecular weight greater than 3,000 daltons. Expanding before membrane formation, permits better control of permeability properties and uniformity of the membrane. The gelled masses within the membrane may be liquified by contacting the capsules with a chelating agent which is preferably ethylene glycol bis-(.beta.-amino ethyl ether)-N,N-tetra-acetic acid. A second membrane layer may be formed by contacting the capsules with a second polycationic polymer. The second membrane may be coated with a polyanionic polymer such as alginate.

Abstract: A modified polysaccharide material which comprises: (1) polysaccharide covalently bonded to a synthetic polymer; (2) the synthetic polymer being made from (a) a polymerizable compound which is capable of being covalently coupled directly or indirectly to said polysaccharide, and (b) one or more polymerizable compounds containing (i) an ionizable chemcial group, (ii) a chemical group capable of transformation to an ionizable chemical group, (iii) a chemical group capable of causing the covalent coupling of the compound (b) to an affinity ligand or a biologically active molecule or (iv) a hydrophobic compound.

Abstract: Apparatus for immobilizing biological cells based on the dielectric properties of biological cells. An inhomogeneous electric field emanating from a grid point location or other contact area is created and attracts the biological cell into contact therewith. Appropriate controls over a series of grid points permits controlled inter-grid point movement of cells thereby permitting sequential testing or sorting processes to be carried out.

Abstract: The invention relates to techniques for isolating from a mixed population of cells disired living cells either producing and releasing a particular product or having a characteristic molecule on their surface. The isolation techniques depend upon the localized interaction between the product (or molecule) and other agents added to the system such that distinguishable conditions can be caused to occur (or not occur) only in the immediate vicinity of desired cells which produced and released the product or which contain the molecule on their surface.

Abstract: The strength of a bead containing microbial cells within a retaining permeable membrane is improved by incorporating finely divided sericitic clay particles within a hydrocolloid-containing composition used to form the membrane. The hydrocolloid is preferably alginic acid, carboxymethyl cellulose, methylethylcellulose or polyvinyl alcohol in an amount of about 10 to 40% by weight.