Abstract: A device for the effective release of cellular moieties, including hormones, wherein a matrix containing a hormone producing cellular moiety is encapsulated with a non-immunogenic polymeric material of poly-para-xylylene or other aromatic based moiety having a membrane portion with a porosity blocking passage therethrough of immunogenic agents and permitting passage therethrough of effective nutrients for said cellular moiety and the hormone produced thereby, an improved matrix for the storage, manufacture, functional testing, and viral infection testing of cellular moieties wherein a collagen based hydrogel is processed to present a liquid phase at host temperature and functions as a substrate for cellular attachment with additives effective for limiting thermal and pressure trauma, and an improved method for the harvesting tissue from organs.

Abstract: A device for the effective release of cellular moieties, including hormones, wherein a matrix containing a hormone producing cellular moiety is encapsulated with a nonimmunogenic polymeric material of poly-para-xylylene or other aromatic based polymeric moiety having a membrane portion with a porosity blocking passage therethrough of immunogenic agents and permitting passage therethrough of effective nutrients for said cellular moiety and the hormone produced thereby, an improved matrix for the storage, manufacture, functional testing, and viral infection testing of cellular moieties wherein a collagen based hydrogel is processed to present a liquid phase at host temperature and functions as a substrate for cellular attachment with additives effective for limiting thermal and pressure trauma, and an improved method for the harvesting tissue from organs.

Abstract: An adsorbent for removing ketoamine-containing protein, which comprises carrying a compound having a terminal functional group of the formula: ##STR1## wherein each of R.sup.1 and R.sup.2 is an organic group and X is 0 or 1, on a porous water-insoluble carrier, a process for removing ketoamine-containing protein by employing the above adsorbent, a process for preventing or treating for diabetic complication by removing ketoamine-containing protein with the above adsorbent and an adsorber for removing ketoamine-containing protein.

Abstract: A process for the preparation of immobilized lipases through reaction on a silica matrix containing non-hydrolyzable organic substituents attached through Si--C bonds.

Abstract: A portable apparatus for detecting the presence of at least one methylxanthine chemical species such as caffeine or theophylline in a beverage comprises a first portion comprising an effective concentration of phosphodiesterase enzyme, a second portion comprising cyclic AMP, and means for indicating inhibition of degradation of the cyclic AMP by the phosphodiesterase due to the presence of the methylxanthine species. A method for determining the presence of at least one methylxanthine chemical species in a beverage comprises contacting at least one test portion of the beverage with effective concentrations of at least one phosphodiesterase enzyme and cyclic AMP, and further contacting the test portion with means for indicating the inhibition of the degradation of the cyclic AMP by the phosphodiesterase due to the presence of the methylxanthine species.

Abstract: A method is provided for preparing polyphosphazene microspheres wherein the polyphosphazene microspheres are produced by coacervation. A solution containing a polyphosphazene is admixed with a solution containing a salt of a monovalent ion such as a salt of a Group I element (for example, NaCl) to form a dispersion containing polyphosphazene coacervate microdroplets. The dispersion then is admixed with a solution containing a salt of a multivalent ion, such as a salt of a Group II element (for example, CaCl.sub.2) to form a suspension of polyphosphazene microspheres. The polyphosphazene microspheres then are recovered from the suspension. Such method enables one to obtain high yields of microspheres having a controlled size distribution. Polyphosphazene microspheres containing biological material can be produced by providing a biological material in the polyphosphazene solution that is mixed with the solution containing a salt of a monovalent ion.

Abstract: Organisms that degrade hydrocarbon-based substances are encapsulated in wax to form organism-containing wax microshells that are used for removing oil-based substances such as oil spills on land and water. The organism is preferably of the genus Candida that produce lipase. The microshell may contain nutrients that sustain the organism. The wax is paraffin wax or beeswax, and the microshell may be coated with talc or carbon powder to provide insulation and to prevent one microshell from sticking to another. When used for remediating an oil spill on water, the microshells are preferably contained in a buoyant container that acts as a flotation device. The flotation device may contain flotation means such as gas-filled microballoons that facilitate flotation.

Abstract: This invention provides novel methods for the formation of biocompatible membranes around biological materials using photopolymerization of water soluble molecules. The membranes can be used as a covering to encapsulate biological materials or biomedical devices, as a "glue" to cause more than one biological substance to adhere together, or as carriers for biologically active species. Several methods for forming these membranes are provided. Each of these methods utilizes a polymerization system containing water-soluble macromers, species which are at once polymers and macromolecules capable of further polymerization. The macromers are polymerized using a photoinitiator (such as a dye), optionally a cocatalyst, optionally an accelerator, and radiation in the form of visible or long wavelength UV light. The reaction occurs either by suspension polymerization or by interfacial polymerization.

Abstract: A core material such as animal tissue or cells is contained within a semipermeable vessel which may be a microcapsule, hollow fiber or plastic membrane having a semipermeable wall by a method that prevents the core material from incorporation into the wall of the vessel. This is accomplished by suspending the core material in a solution of polysaccharide gum such as an alkali metal alginate in an amount between about 0.2% and about 0.5%, removing and washing the core material to remove all but a thin layer of polysaccharide gum, and gelling the polysaccharide gum with multivalent cations or other means to form a pretreated core material.

Abstract: Methods and compositions are provided for controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the bioartificial organ with extracellular matrix molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

Abstract: The present invention is directed to a macrocapsule for encapsulating microcapsules containing biologically active material, such as living cells or free living cells, to make the system more biocompatible by decreasing the surface area and surface roughness of microencapsulated biological materials; increasing mechanical stability of microencapsulated biological materials; enhancing cytoprotectivity by increasing diffusion distance of encapsulated biological material from cytotoxins secreted in vivo; providing retrievability of microencapsulated material; and providing a system of sustained release of the cellular products. The method for producing such a macrocapsule containing the microcapsules is also disclosed.

Abstract: A biocompatible capsule for containing cells for implantation is prepared containing an inner support that provides tensile strength to the capsule. The capsule may be a tubular semipermeable membrane such as a hollow fiber membrane having both ends sealed. A rod shaped inner support extends through the lumen and ends of the rod are attached to sealed ends of the fiber. Prior to sealing one fiber end, cells are introduced into the lumen. Cells within the capsule may be suspended in a liquid medium or immobilized in a hydrogel or extracellular matrix material, and biologically active molecules can be delivered from the capsule to surroundings or from the surroundings into the capsule. The inner support may have external features such as flutes or a roughened or irregularly-shaped surface, and may be coated with cell-adhesive substance or a cell-viability-enhancing substance.

Abstract: This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. A particular embodiment is directed to derivatizing or adsorbing polyethylene oxide-poly(dimethylsiloxane) copolymer (PEO-PDMS) onto a surface within the bioartificial organ to inhibit cellular attachment.

Abstract: The disclosed invention is a device for adhering cells in a specific and predetermined position. The device comprises a plate defining a surface and a plurality of cytophilic islands that adhere cells which are isolated by cytophobic regions to which cells do not adhere and further is contiguous with the cytophilic islands. The islands or the regions or both may be formed of a self-assembled monolayer (SAM). Further, the cytophobic regions are wide enough such that less than 10 percent of the cells adhered to the cytophilic islands are allowed to form bridges across the cytophobic regions and contact each other. The device is used in a method for culturing cells on a surface or in a medium and also for performing cytometry. Furthermore, the device is used in immobilization of cells at a surface and for controlling the shape of a cell.

Abstract: A system for electrochemical measurement of glucose concentration in an undiluted test sample, e.g. blood is provided containing a sensor including a three-layered contiguous membrane. The membrane has a thickness of 50 to 130 microns, and is composed of a 1 to 10 micron thick first layer, a 10 to 30 micron thick second layer having an average pore diameter of 15 nanometers and a 40 to 80 micron thick third layer containing glucose oxidase. The third layer is less dense than the first and second layers and the first layer is more dense than the second layer. The layers of the membrane are fused together such that no clear distinction can be made between the layers at the boundary. The sensor is calibrated in a standard glucose solution which includes catalase as a hydrogen peroxide scavenger, and the sensor has a response that is linear throughout the concentration range of glucose in an undiluted sample.

Abstract: A biocompatible capsule for containing cells for implantation is prepared containing an inner support that provides tensile strength to the capsule. Cells within the capsule are suspended in a liquid medium or immobilized in a hydrogel or extracellular matrix material, and are surrounded by a semipermeable membrane across which biologically active molecules can be delivered from the capsule to surroundings or from the surroundings into the capsule. The inner support may be formed as an integral part of the capsule during a coextrusion process to form the capsule. Alternatively, the inner support may be a discrete component within a tube having top and bottom sealing fittings that are linked withing the tube by the support. The inner support may have external features such as flutes or a roughened or irregularly-shaped surface, and may be coated with cell-adhesive substance or a cell-viability-enhancing substance.

Abstract: A reaction chamber is constructed of a reactant-containing aqueous solution, which may be in droplet form, coated with a fluoropolymer powder such as Polytetrafluoroethylene (PTFE), preferably having a particle size of less than 500 microns. After a reaction, the droplet is destroyed by adding a substance such as a detergent or organic solvent, and the fluoropolymer powder is removed by centrifuging and filtering. Using a micropipette, size of the droplet chamber is increased or decreased by removing or adding liquid, or liquid is transferred from one droplet chamber to another. Charcoal, metal powder or silica powder can be inserted inside or on the surface of the droplet. A droplet chamber containing a first reactant such as an enzyme-bound bead is combined with a second droplet chamber containing a second reactant to react the first and second reactants. A dialysis chamber contains a filtration membrane in contact with the droplet chamber.

Abstract: A method is provided for immobilization of whole microbial cells containing enzymes in Ca-alginate capsules. Whole microbial cells are mixed with a CaCl.sub.2 solution, a small amount of xanthan gum is added, the resultant mixture is added drop-wise while stirring to a Na-alginate solution containing a small amount of surfactant which is preferably polyoxyethylenesorbitan monolaurate to obtain the capsules containing the cells. The capsules may be washed with distilled water, hardened by in a CaCl.sub.2 solution and incubated in a growth medium. The microbial cells are bacteria or fungi cells and may be recombinant cells.

Abstract: The present invention is directed to a macrocapsule for encapsulating microcapsules containing biologically active material, such as living cells or free living cells, to make the system more biocompatible by decreasing the surface area and surface roughness of microencapsulated biological materials; increasing mechanical stability of microencapsulated biological materials; enhancing cytoprotectivity by increasing diffusion distance of encapsulated biological material from cytotoxins secreted in vivo; providing retrievability of microencapsulated material; and providing a system of sustained release of the cellular products. The method for producing such a macrocapsule containing the microcapsules is also disclosed.

Abstract: The present invention pertains to an oriented tissue-equivalent formed by contracting a collagen solution with connective tissue cells. In the method of the present invention, the contraction of collagen fibrils by the connective tissue cells is restrained along an axis of cell alignment defined by at least two structural members within the gel, whereby the connective tissue cells align along the axis thereby producing an oriented tissue-equivalent.

Abstract: L-tertiary-Leucine and L-phosphinothricine are obtainable by transamination of the corresponding keto acids as a precursor in the presence of amino acids as amino group donors. The reaction is preferably carried out with microorganisms or their transaminases.

Abstract: Cells for implantation into a patient are packaged within a barrier of immunoprotective tissue prior to implantation to obviate or minimize rejection of the cells. The preferred immunoprotective tissue for forming the barrier is cartilage. The tissue is formed into a layer that is thin enough to allow diffusion of nutrients and gases into the center of a cell mass packaged within the immunoprotective tissue. Typically the layer is less than 300 microns, preferably between 5 and 20 microns. Cells to be implanted, typically dissociated parenchymal cells including hepatocytes, Islets of Langerhans, or other cells having metabolic functions, are then placed on the tissue layer, and the layer is folded to seal the cells to be implanted within the tissue layer. In the preferred embodiment, the dissociated cells are first seeded onto a polymeric fiber matrix.

Abstract: Living animal tissue cells and microbial cells such as yeast cells are encapsulated in an inorganic gel prepared from an organosilicon. Encapsulation of tissue cells is performed by mixing an organosilicon precursor with a highly acidic aqueous solution to hydrolyze the organosilicon precursor and provide a gel forming solution, cooling the gel forming solution, forming a mixture of living tissue cells and Hank's balanced salt solution, adding a base solution to the gel forming solution, immediately thereafter adding the mixture containing tissue cells to the gel forming solution, and pouring the resultant mixture into a container where an inorganic gel forms encapsulating the tissue cells. The organosilicon precursor may be tetraethoxysilane, tetrabutoxysilane, tetramethoxysilane or tetrapropoxysilane.

Abstract: A porous carrier for biocatalysts (a) comprising a water-insoluble inorganic filler and a polyolefine binder selected from polyethylene and polypropylene, (b) having open pores allowing cells to penetrate and grow within its pores, and (c) having a density above 1 g/cm.sup.3.

Abstract: An enzyme-containing granulate is prepared containing a core and a shell wherein the core and/or shell contain an enzyme and the shell contains artificial or cellulose fibers in an amount of 1.5-40%. The core may also contain the fibers in an amount of 1.5-40%. In a preferred embodiment, the core contains a primary enzyme, the fibers, a coating of a sustained release agent, and the shell contains a secondary enzyme and the fibers. The sustained release coating causes the primary enzyme to be released more slowly than the secondary enzyme in a washing solution. In another embodiment, the core contains a primary detergent additive, a coating of a protective agent, and the shell contains a secondary detergent additive and the fibers. The protective coating separates the primary and secondary detergent additives so they do not harm each other during storage. Preferably, the core and shell also contain a binder, a filler and a granulating agent.

Abstract: A permselective graft polymer is disclosed that is formed by converting into intermediate reactive sites a portion of the cyano groups of a backbone polymer and grafting polyalkylene oxide polymer chains to the backbone polymer through the reactive sites. Either the backbone polymer of a polymer resin or a permselective polymer membrane can be grafted. When a resin is used, it is formed into a permselective polymer membrane using known methods. The resulting permselective membrane can be formed into hollow fibers or flat sheets for the encapsulation of living cells. The encapsulated cells are then implanted into a patient in need of the biologically-active factors produced by the cells. The permselective graft polymer membrane exhibits good molecular diffusion with minimal protein adsorption.

Abstract: Organic enzyme solutions comprise an ion pair complex of an enzyme and a surfactant, and an organic solvent in which the enzyme-surfactant ion pair is dissolved. The solution has catalytic activity at least an order of magnitude greater than a suspension of an equal amount of the enzyme and organic solvent without ion pair complexes. The enzyme is preferably a hydrolase with an acyl transferase activity and the surfactant is Aerosol OT (sodium bis(2-ethylhexyl) sulfosuccinate) at low concentrations.

Abstract: Animal cells are cultured while embedded in a collagen gel. The gel containing cells is formed by dispersing animal cells in a collagen solution, placing a drop (or drops) of the cell-containing collagen solution on a support surface and allowing the drop to gel to fix on the surface as a globular collagen gel having a convex surface. The cells are cultured by contacting the gel with a culture medium that may be serum-free or contain dextran sulfate. The drop preferably contains about 3 to about 300 microliters of the collagen solution and is about 2 mm or less in height. The cells may be precultured on a support surface having a collagen layer, released from the collagen layer by treatment with collagenase and dispersed in the collagen solution. The cells can be evaluated after culturing by staining such as with neutral red, or with fluorescein diacetate and irradiating, or by photographing cells in the collagen gel.

Abstract: A cell-polymeric solution is injected into an animal where the polymer crosslinks to form a polymeric hydrogel containing dispersed cells and the cells form new tissue in the animal. The polymer is biodegradable and is a natural polymer such as alginate or a synthetic polymer. The cells are chondrocytes, osteoblasts, muscle cells, fibroblasts or cells acting primarily to synthesize, secret or metabolize materials. Crosslinking of the polymer results from using cations or anions, altering the pH or changing the temperature. A polyion such as polyethyleneimine or polylysine can be added before injection to stabilize the polymeric hydrogel. A kit for tissue formation is provided by combining the cell-polymeric solution with a means for injecting the solution into an animal.

Abstract: Cells having enzyme activity, and the enzyme activity thereof, are preserved for a prolonged period of time, as a suspension of microbial cells or as a suspension of immobilized cells in particles, in an aqueous medium that is a neutral or weakly basic aqueous solution of inorganic salts, having a molarity ranging from 100 mM to the saturation concentration of the inorganic salts. Preferably, the microbial cells are cells containing the enzyme, nitrile hydratase or nitrilase, such as Gordona terrae or Rhodococcus rhodochrous, and the inorganic salts are phosphates, borates, sulfates, sulfites or hydrochlorides. The present invention provides an industrially useful method for preserving a large quantity of cells or immobilized cells in particles having nitrile hydratase or nitrilase enzyme activity for a prolonged period of time (e.g., 300 days) without cell lysis or enzyme deterioration even at room temperature.

Abstract: The present invention relates to a new form of biocompatible materials (e.g., lipids, polycations, polysaccharides) which are capable of undergoing free radical polymerization, e.g., by using certain sources of light; methods of modifying certain synthetic and naturally occurring biocompatible materials to make polymerizable microcapsules containing biological material coated with said polymerizable materials, composites of said polymerizable materials, methods of making microcapsules and encapsulating biological materials therein, and apparatus for making microcapsules containing biological cells (particularly islets of Langerhans) coated with polymerizable alginate or with a composite thereof (e.g., alginate and PEG). The present invention also relates to drug delivery systems relating to the foregoing, as well as bioadhesives and wound dressings made utilizing the foregoing technology.

Abstract: The present invention relates to a method of screening chemotherapeutic agents in vivo. The method comprises implanting into a laboratory animal a biocompatible, semi-permeable encapsulation device containing a target cell-line, treating the laboratory animal with a test agent, then evaluating the target cells for reaction to the test agent.

Abstract: Living tissue cells such as animal or plant tissue cell are encapsulated in an inorganic gel by mixing an organosilicon precursor with an aqueous acidic solution to form a gel forming solution and hydrolyze the organosilicon precursor, cooling the gel forming solution, forming a mixture of living tissue cells and Hank's balanced salt solution, adding a base solution to the gel forming solution to form a mixture, immediately thereafter adding the mixture containing living tissue cells to the mixture containing the gel forming solution, and pouring the resultant mixture into a container where an inorganic gel forms encapsulating the cells. The organosilicon precursor may be tetraethoxysilane, tetrabutoxysilane, tetramethoxysilane or tetrapropoxysilane.

Abstract: A transplant with a core of a viable, physiologically active, cell(s) and a non-fibrogenic coating of alkaline earth metal alginate having a high mannuronate to guluronate molar ratio and free from fibrogenic amounts of fucose, sulfate, phloroglucinol and protein moieties. The coating has a permeability sufficiently low and a thickness sufficiently large to protect the tissue cells from host immunological agents after transplantation, the coating also being sufficiently permeable and thin to permit the diffusion of cell sufficient nutrients and cell products through the coating required for cell viability. The alginate coating can be reacted with polylysine to form a polylysine-alginate complex on the outer surface thereof. The complex can then be reacted with polyaspartic acid to provide a physiologically acceptable negative surface charge.

Abstract: An improvement in enzyme linked immunoassays is disclosed wherein the enzyme is in the form of a water soluble polymer saccharide conjugate which is stable in hostile environments. The conjugate comprises the enzyme which is linked to the polymer at multiple points through saccharide linker groups.

Abstract: A method and apparatus for carrying out affinity purification of a ligate. The method comprising, (a) providing a ligate containing liquid to a first side of at least one porous hollow fiber membrane with a ligand immobilized thereto that binds and separates the ligate from the liquid, (b) withdrawing a first portion of the liquid from the first side of the porous hollow fiber membrane, (c) recirculating the first portion of liquid to the first side of the porous hollow fiber membrane, (d) repeating steps (a) to (c) until a majority of the liquid has flowed through the porous hollow fiber membrane, and (e) providing an elution solution to one side of the porous hollow fiber membrane under a pressure sufficient to cause the elution solution to flow into and through the membrane to effect disassociation of any ligate-ligand bonds wherein any ligate bound to the ligand is eluted with the elution solution.

Abstract: Insoluble supports are prepared which possess high surface areas and efficiently dispersed isocyanate groups. These reactive supports are useful for covalently binding proteins which preferably are enzymes and provide catalysts for conducting organic reactions.

Abstract: A composition including a polyester containing one or more free COOH groups ionically conjugated with a bioactive polypeptide comprising at least one effective ionogenic amine, wherein the polyester contains a member selected from the group of L-lactic acid, D-lactic acid, DL-lactic acid, .epsilon.-caprolactone, p-dioxanone, .epsilon.-caprolic acid, alkylene oxalate, cycloalkylene oxalate, alkylene succinate, .beta.-hydroxybutyrate, substituted or unsubstituted trimethylene carbonate, 1,5-dioxopan-2-one, 1,4-dioxepan-2-one, glycolide, glycolic acid, L-lactide, D-lactide, DL-lactide, meso-lactide, and any optically active isomers, racemates or copolymers thereof, and at least 50%, by weight, of the polypeptide present in the composition is ionically conjugated to said polyester.

Abstract: A method for encapsulating biological substances in biocompatible microcapsules is disclosed, the method comprising:(a) maintaining a coating-forming liquid film sheet transverse to a vertical plane, said sheet comprising an organic polymerizable monomer liquid,(b) causing droplets comprising biological substances in an aqueous medium to fall downwardly through said liquid film sheet to form microcapsules comprising cores of said droplets coated by said film,(c) permitting said microcapsules to fall downwardly from said liquid film sheet, and(d) polymerizing said liquid film coatings during descent of said microcapsules below said sheet to form a permeable polymer coating of a sufficient structural integrity so that said microcapsules are self-supporting.

Abstract: An electrostatic process is used for coating a biological material with a uniform, continuous polymer layer by discharging a suspension of the biological material in a gelable coating polymer solution in a continuous stream through an orifice into an electrostatic field. The stream is attenuated to form droplets by maintaining an electrostatic voltage between the needle and the gelling solution which is sufficient to maintain an attraction of at least 1.times.10.sup.-6 newtons on the stream of liquid leaving the needle, and the droplets are collected in a gelling solution. A preferred product is pancreatic islets having a continuous, smooth coating of high polymannuronate non-fibrogenic alginate having a thickness less than 200 .mu.m such as about 20-200 .mu.m. The alginate preferably contains less than 1 wt. % fucose, less than 0.5 wt. % sulfate and less than 0.01 wt. % phloroglucinol, is free of fibrinoogenic concentration of protein, and has a mannuronate to guluronate ratio of from 1.2 to 6.

Abstract: A latent growth factor such as transforming growth factor beta (TGF.beta.) is converted to active form by matrix vesicles or an extract from matrix vesicles. The matrix vesicles may be stimulated with a Regulator of Enhancing Factor (REF) such as 1,25-dihydroxy vitamin D (1,25-(OH).sub.2 D.sub.3) or steroid hormones which may be intercalated into the vesicle membrane. The latent growth factor may be activated in culturing cells such as chondrocytes that have been pretreated with 24,25-(OH).sub.2 D.sub.3 to activate cell differentiation, or in healing of bone or cartilage defects, and activation can be carried out in vivo or in vitro. Biodegradable polymeric implants may be prepared containing latent growth factor, REF, matrix vesicle or matrix vesicle extract.

Abstract: A supported polyionic hydrogel containing biologically active material is epared by impregnating into a porous support material a solution of anionic polysaccharide, a solution of cationic polysaccharide and a biologically active material. The anionic polysaccharide and the cationic polysaccharide react with each other to form a hydrogel containing the biologically active material. The hydrogel may be dried such as by lyophilization. The biologically active material can be in either polysaccharide solution or in another solution impregnated into the porous support material. A paper material or a textile material may be used as the porous support material. Preferably, the anionic polysaccharide is xanthan, dicarboxystarch or dicarboxycellulose and the cationic polysaccharide is chitosan. Especially preferred is a hydrogel formed from xanthan and chitosan.

Abstract: A reagent such as a heat resistant enzyme is entrapped in a material such as wax or a liposome that releases the reagent when heated so the reagent is available for reaction. In a preferred embodiment, wax beads containing the reagent are prepared by injecting the reagent into beads of molten wax and cooling to solidify the wax. In another embodiment, droplets of a solution of the reagent are dropped through a layer of molten wax to coat the droplets with the wax and the coated droplets are cooled to solidify the wax. The entrapped reagents have application in nucleic acid hybridizations, polymerase chain reactions (PCR), reverse transcriptase reactions (RTR), nucleic acid sequencing, and product generating reactions such as colorimetic, fluorometric and chemiluminescent enzyme labeled immunoassays.

Abstract: Elongated seamless capsules containing biological material are prepared by a method in which a coagulant, which includes a cell suspension or other biological material, and a polymeric casting solution are extruded through a common extrusion port having at least two concentric bores, such that the coagulant is extruded through an inner bore and the polymeric casting solution is extruded through an outer bore. Extrusion of the coagulant is initiated subsequent to initiating delivery of the casting solution to form a capsule having a curved and smooth leading edge shape. Delivery of the coagulant is then shut off, and extrusion of the casting solution is terminated either immediately or after some predetermined time. This procedure can be modified to form in the capsule a coaxial rod that is connected to one end but not the other end of the capsule.

Abstract: A coating apparatus includes a rotary cup for forming beads and projecting them radially outwardly, and one or more collection basins surrounding the bead forming cup. The cup is adjustably rotatable about its central axis, and the collection basins are independently rotatable and positioned to collect the beads projected from the cup. The coating apparatus further includes an elevation adjustment system for axially adjusting the alignment of the cup with respect to the selected collection basins. The rotational speeds of the cup and the collection basins are selected so as to minimize the impact of the beads against a gelling solution in the collection basins. In use, a supply mixture is introduced into a mixing chamber of the cup. As the cup spins, the coated particles are propelled upwardly by the centrifugal force from the mixing chamber along the inner surface of the cup, and are projected radially outwardly, as beads, into the gelling solution in one of the selected basins.

Abstract: Biological agents such as secretory cells are encapsulated in a hydrophilic gel made of agarose or collagen-agarose and gelatin sponge-agarose combinations. In a preferred embodiment, semi-solid beads are formed from a suspension containing collagen, agarose and secretory cells such as pancreatic islets, the collagen is polymerized to form solid, agarose-collagen beads and the solid beads are coated with agarose. Coating is preferably by rolling the solid beads in about 5-10% agarose, contacting the rolled beads with mineral oil and washing oil from the beads. Beads containing secretory cells can be transplanted into a mammal to treat a condition caused by impaired secretory cell function.

Abstract: A process and apparatus are provided for making solid Particles from an ionically cross-linkable material by cross-linking drops of the material with a cross-linking agent in the form of a falling stream. In one embodiment, a stream of the cross-linking agent flows down the inner walls of an enclosure and drops of the material are directed to the stream of cross-linking agent. In another embodiment, a stream of the cross-linking agent is free-falling by gravity in a cascade without contacting any surface and drops of the material are directed to the stream of cross-linking agent. Solid particles are separated from the cross-linking agent at about the bottom of the enclosure or at about the bottom of the cascade. The drops of cross-linkable material are directed at the stream of cross-linking agent preferably at an angle of incidence of less than 90.degree. such as between 5.degree. and 45.degree. and most preferably between 15.degree. and 30.degree.. Particles having a size of 10 .mu.

Abstract: A polysaccharide gel enclosing microorganisms is soaked in a solution of a high concentration such as at least 500 g/l of hydrophilic substance and the gel is at least partially dehydrated to provide improved viability of the microorganisms after storage and rehydration of the gel. The dehydration may be carried out in a fluidized bed or by lyophilization. The gel may be in the form of beads or fibers having a double layer structure formed by an internal layer or core of gel containing the microorganisms and an external layer or envelope of gel essentially devoid of the microorganisms. The hydrophilic substance can be a low molecular weight polyol such as glycerol or a sugar such as sucrose, glucose or fructose. The microorganisms in the gel are preferably yeasts and after rehydration the yeast-containing gel is used in the secondary fermentation of wine to produce sparkling wine or champagne.

Abstract: A polysaccharide gel enclosing microorganisms is soaked in a solution of a high concentration such as at least 500 g/l of hydrophilic substance and the gel is at least partially dehydrated to provide improved viability of the microorganisms after storage and rehydration of the gel. The dehydration may be carried out in a fluidized bed or by lyophilization. The gel may be in the form of beads or fibers having a double layer structure formed by an internal layer or core of gel containing the microorganisms and an external layer or envelope of gel essentially devoid of the microorganisms. The hydrophilic substance can be a low molecular weight polyol such as glycerol or a sugar such as sucrose, glucose or frutose. The microorganisms in the gel are preferably yeasts and after rehydration the yeast-containing gel is used in the secondary fermentation of wine to produce sparkling wine or champagne.

Abstract: A biocompatible microcapsule containing living cells encapsulated in a membrane is disclosed. The membrane is a complex formed by the cohesion of two polymer layers. An inner layer comprises a substrate biopolymer and an outer layer comprises a synthetic polyelectrolyte having an electrolytic charge opposite that of the substrate biopolymer. Droplets of a solution of substrate biopolymer containing a suspension of living cells can be added to a solution comprising the synthetic polyelectrolyte to form the encapsulates. The membrane is formed by the cohesion of the oppositely-charge polymer layers to form a complex of substrate biopolymer and synthetic polyelectrolyte. Preferably, the inner layer contains a cationic biopolymer, such as collagen modified to have a pKI of 9, or an anionic biopolymer such as esterified or modified hyaluronic acid.