Abstract: The present invention relates to bioreactors for root organ cultures that enable large parts of the inoculation or biomass transfer, cultivation and harvest of the cultures to be performed outside of an aseptic environment. The present invention further relates to methods of producing and aseptically harvesting roots, and methods of producing root cultures using the aforementioned bioreactors alone or as part of an apparatus further comprising an inoculation vessel or at least one further bioreactor.

Abstract: A culture device and a culture method by which a substance to be cultured can be three-dimensionally cultured, and the substance thus cultured can be removed as an integrated product with multiple tubes; and a cultured organ produced by the culture method. The culture device comprises a sealed container (2) which contains the substance to be cultured (A) and is disassembled after the culture is completed; multiple ducts (3, 4, 5) arranged in the sealed container (2) and having a plurality of micropores formed on the outer peripheral surface; a culture medium-feeding device (6, 7) for feeding/circulating the culture medium (B) to at least one duct (3 or 5); an excretory device (8) connected to at least one duct (4) for excreting the waste product (C)permeating into the duct (4) through the micropores of the duct (4) from the substance to be cultured to the outside of the sealed container.

Abstract: A product concentration device that utilizes a reservoir connected to a hollow-fiber filter element where the reservoir can serve as a container for filtrate emanating from another filtering device, such that product in the reservoir can be stored, concentrated and/or further processed as desired. Enclosed reactor systems, each of at least three chambers, fluid flow between the chambers controlled by selectively permeable barriers, flow controlled by an alternating flow diaphragm pump.

Abstract: Systems and methods for containing and manipulating liquids, including vessels and unit operations or components of cell culture, cell containment, bioreactor, and/or pharmaceutical manufacturing systems, are provided. The apparatus may include a disposable, collapsible bag adapted for containing a liquid, the collapsible bag in fluid communication with a liquid-solids (e.g., cell) separation device. For example, an outlet of the collapsible bag may be connected to an inlet of the separation device, and an outlet of the separation device may be connected to an inlet of the collapsible bag for recycle. Accordingly, after separating the cells from the liquid in the separation device, the cells can be flowed back into the collapsible bag where they can be re-harvested. Meanwhile, product contained in the liquid can be collected in a separate container. The efficiency of product formation in such a system may be enhanced by using mixing systems described herein.

Abstract: A method for manufacturing a shaped cross-linked hyaluronic acid product including the step of subjecting a non-cross-linked precipitated hyaluronic acid substrate in a desired shape to a single cross-linking reaction in a liquid medium having a pH of 11.5 or higher and including one or more polyfunctional cross-linking agent(s) and an amount of one or more organic solvent(s) giving precipitating conditions for hyaluronic acid, under suitable conditions to obtain a precipitated, shaped cross-linked hyaluronic acid product having a degree of modification of 1-40 cross-linking agent units per 1000 disaccharide units.

Abstract: The present invention relates to a kit and a method of linear amplification of a least one nucleic acid target in a sample, said method comprising: (a) contacting each target in the sample with a nucleic acid polymerase and a primer comprising a component preventing copying of the primer by the nucleic acid polymerase; and at least one nuclease blocking nucleotide; (b) generating a primer extension product; (c) preventing priming by the 3?-end of the primer extension product, and (d) repeating steps b) and c) at least once.

Abstract: The invention provides methods and reagents for detecting luciferase in biological samples. The methods and reagents of the present invention allow detecting fungal luciferase or a functional analog thereof.

Abstract: A membrane photobioreactor for treating nitrogen and phosphorus that are out of limits in a biogas slurry and treating method thereof, relating to biogas slurry treatment. The membrane photobioreactor for treating nitrogen and phosphorus that are out of limits in a biogas slurry is provided with a biogas slurry storage tank, peristaltic pumps, a microalgae cultivating tank, an air pump, a membrane photobioreactor and a hollow fiber membrane.

Abstract: Bone cages are disclosed including devices for biocompatible implantation. The structures of bone are useful for providing living cells and tissues as well as biologically active molecules to subjects.

Abstract: Cell expansion systems and methods of use are provided. The cell expansion systems generally include a hollow fiber cell growth chamber, and first and second circulation loops (intracapillary loops and extracapillary loops) associated with the interior of the hollow fibers and exterior of the hollow fibers, respectively. Detachable flow circuits and methods of expanding cells are also provided.

Abstract: A nanostructure composed of a plurality of peptides, each peptide containing at least one aromatic amino acid, whereby one or more of these peptides is end-capping modified, is disclosed. The nanostructure can take a tubular, fibrillar, planar or spherical shape, and can encapsulate, entrap or be coated by other materials. Methods of preparing the nanostructure, and devices and methods utilizing same are also disclosed.

Abstract: The present invention provides a hepatic lobule-like bioreactor. The bioreactor includes a nanofiber scaffold enclosed within a housing. An intrahepatic fibrous vascular network, a bile capillary network, upper hepatic bile ducts, lower hepatic bile ducts, a common bile duct connecting the upper and the lower hepatic bile ducts, and collagen fibrous microchannels for hepatocytes surrounded by the bile capillary network are distributed throughout the nanofiber scaffold. Bile capillaries in the bile capillary network are provided with two or more inlet ports for biliary epithelial cells. The collagen fibrous microchannels for hepatocytes are provided with two or more inlet ports for hepatocytes. The intrahepatic vascular network is provided with a liquid inlet port and a liquid outlet port. These ports extend through the housing.

Abstract: A bioartificial kidney equivalent and a process for producing the bioartificial kidney equivalent. The hybrid bioartificial kidney comprises human proximal and distal renal tubule cells grown on particular synthetic membranes.

Abstract: A fiber includes one or more layers of polymer surrounding a central lumen, and living animal cells disposed within the lumen and/or within at least one of the one or more layers, wherein the fiber has an outer diameter of between 5 and 8000 microns and wherein each individual layer of polymer has a thickness of between 0.1 and 250 microns. Also disclosed are model tissues including such fibers, and method of making such fibers. The fibers can serve as synthetic blood vessels, ducts, or nerves.

Abstract: The present invention provides a device for activating a self-contained biological indicator. The biological indicator includes a casing, an ampule having a growth-promoting medium disposed therein and microorganisms. The ampule and microorganisms are disposed within the casing. The device is comprised of a first lever arm having a cavity formed therein. The cavity is dimensioned to receive a biological indicator. A second lever arm has a protrusion extending from a surface thereof and is moveable relative to the first lever arm to deform a casing of the biological indicator thereby fracturing an ampule in the casing and exposing microorganisms in the casing to a growth-promoting medium in the ampule of the biological indicator.

Abstract: Two cell lines, PICM-19H and PICM-19B, were derived from the bipotent ARS-PICM-19 pig liver stem cell line. The unipotent porcine stem cell line PICM-19H differentiates exclusively into hepatocytes and can be induced to express CYP450 enzymes. The growth rate and cell density in culture, morphological features, and hepatocyte detoxification functions, i.e., inducible CYP450 activity, ammonia clearance, and urea production of the PICM-19H cells were evaluated for their application in artificial liver devices. PICM-19H cells contain numerous mitochondria, Golgi apparatus, smooth and rough endoplasmic reticulum, vesicular bodies and occasional lipid vacuoles and display inducible CYP450 activity, clear ammonia, and produce urea in a glutamine-free medium. The data indicate that both cell lines, either together or alone, may be useful as the cellular substrate for an artificial liver device. The results demonstrate the potential for the use of PICM-19H cells in drug biotransformation and toxicity testing.

Abstract: Diatom devices are disclosed including devices for biocompatible implantation. The diatom structures are useful for providing living cells and tissues as well as biologically active molecules to subjects.

Abstract: The invention is directed to producing large numbers of cells using hollow fiber bioreactor technology. The cells are non-embryonic stem, non-germ cells that can be characterized by one or more of the following: extended replication in culture and markers of extended replication, such as telomerase, markers of pluripotentiality, and broad differentiation potential, without being transformed.

Abstract: A manipulation tool is disclosed for producing cell material having multiple biological cells, which have a predefined geometrical arrangement. The tool includes a tool body, whose surface at least partially contacts the cell material, and a setting device for adjusting the tool body by a continuous expansion, so that geometrical properties of the surface change and an interior of the tool body is enlarged. The setting device is adapted to expand the tool body at an advance velocity in a range from 0.1 ?m/h to 1 mm/h.

Abstract: In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, embodiments of the present disclosure, in one aspect, relate to methods of making a structure including nanotubes, a structure including nanotubes, methods of delivering a fluid to a cell, methods of removing a fluid to a cell, methods of accessing intracellular space, and the like.

Abstract: The invention relates to a process for the culturing of cells, preferably E1-immortalized HER cells, more preferably PER.C6 cells in a reactor in suspension in a cell culture medium, wherein the cells produce a biological substance, preferably an antibody, wherein at least one cell culture medium component is fed to the cell culture and wherein the cell culture comprising the cells, the biological substance and cell culture medium is circulated over a separation system and wherein the separation system separates the biological substance from substances having a lower molecular weight than the biological substance and wherein the biological substance is retained in or fed back into the reactor. Preferably part of the substances of lower molecular weight is continuously removed from the cell culture.

Abstract: A device for culturing, storing and expanding adherent renal cells. The device permits the adhesion and proliferation of the cells and the surface characteristics of the membrane material used in said device further permit the cellular matrix components (EMC). A method for expanding adherent renal cells and methods of using particular membranes for culturing, storing and expanding adherent renal cells. The membranes comprise a copolymer of acrylonitrile and sodium methallyl sulfonate as well as polyethylenimine.

Abstract: The invention relates to a process for the culturing of cells, preferably E1-immortalized HER cells, more preferably PER.C6 cells in a reactor in suspension in a cell culture medium, wherein the cells produce a biological substance, preferably an antibody, wherein at least one cell culture medium component is fed to the cell culture and wherein the cell culture comprising the cells, the biological substance and cell culture medium is circulated over a separation system and wherein the separation system separates the biological substance from substances having a lower molecular weight than the biological substance and wherein the biological substance is retained in or fed back into the reactor. Preferably part of the substances of lower molecular weight is continuously removed from the cell culture.

Abstract: The present invention relates to a method for preparing fibers, notably of polysaccharide or collagen, by wet spinning under coagulation, said method notably comprising: a step for extruding a coagulable macromolecular assembly solution through a normal die; at least one partial coagulation cycle comprising a coagulation step on the one hand and a step for interrupting the coagulation on the other hand; and a step for receiving, notably by winding up, the obtained hollow fiber. The invention also relates to multi-membrane hollow fibers consisting of a same macromolecular assembly which may be spun by coagulation, notably a natural or modified natural polysaccharide in the physical hydrogel or partly dehydrated state. Said fibers including at least over their length two superposed coaxial membranes separated from each other by an inter-membrane space. The invention also relates to the spinning device for applying said method.

Abstract: A membrane supported bioreactor arrangement and method for anerobic conversion of gas into liquid products including membrane modules having hollow fibers, each of the hollow fibers formed from an asymmetric membrane wall having a porous outer layer defining biopores for retaining a porous biolayer about the outer surface of the membrane wall and a less permeable hydration layer around the hollow fiber lumen; a membrane vessel for retaining the membrane modules in a process gas for formation of the biolayer on the outer surface of the hollow fiber wall by interaction of microorganisms with a process gas and for the production of a liquid product, wherein the membrane vessel retains the membrane modules in a common horizontal plane; provides a seal between contents of the membrane tank and ambient atmosphere; and includes a liquid supply conduit for communicating the process liquid with the hollow fiber lumens of the hollow fibers.

Abstract: The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.

Abstract: A perfusable bioreactor is used for the production of human tissues, animal tissues or tissue equivalents. Their production is based on a structure cultivated in the interior, the interior being enclosed by an envelope and containing at least one inlet and one outlet for a liquid nutrient medium. Accordingly, the bioreactor can be connected to a unit for producing a perfusion pressure of the nutrient medium. This tissue replacement is particularly suitable for use in clinical/therapeutical applications.

Abstract: The present invention relates to filtration devices and related methods of use. In particular, the present invention relates to implantable filtration devices used, for example, for filtering impurities from a body fluid of a subject.

Abstract: The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.

Abstract: A method for producing cell material (20) having multiple biological cells (21), which have a predefined geometrical arrangement, includes the steps of providing a manipulation tool (10) having a tool body (11), whose surface (12, 14) at least partially contacts the cell material (20), and adjusting the manipulation tool (10) using a change of geometrical properties of the surface (12, 14) in such a way that the geometrical arrangement of the cells (21) is changed. A manipulation tool for performing a method of this type is also described.

Abstract: To provide a cell-filled device that is suitable for use in, for example, an implantable or circulation type hybrid artificial organ. In a cell-filled device including hollow fiber membranes whose hollow portions are filled with cells, the hollow fiber membranes have modified cross sections, and a cell aggregate provided in each of the hollow portions has cells formed into two or more layers in arbitrary directions, provided that the distance from an arbitrary point of the cell aggregate to the nearest inner wall of hollow fiber membrane is less than 75 ?m. This cell-filled device enables effective use of cells without the necrosis thereof. Further, according to the present invention, there is provided a method of manufacturing the cell-filled device.

Abstract: Provided are tubular structures of a biocompatible, triggerably-dissolvable material such as cellulose or a copolymer having an LCST below physiological temperatures. The structures may be embedded within a cell growth scaffold. The tubular structures are useful in growing 3-dimensional tissue structures because nutrients, cytokines or other cell growth and/or differentiation compounds, as well as drugs, such as antibiotics and steroids, can be administered over time, and the tubular structures can be dissolved non-invasively.

Abstract: A method of immunomodulation by contacting the bodily fluid of a patient with renal tubule cells outside of the kidney.

Abstract: The present invention relates to treatment of polymeric bioreactor surfaces, to promote the proliferation of adherent cells.

Abstract: A method and apparatus for preparing biological cell samples for intracellular analysis. The invention is based upon the recognition that many of the steps of the conventional methods for such sample preparation can be eliminated, leading to a process that readily lends itself to automation and the advantages associated therewith. The method of the invention comprises the steps of (a) cell-fixation, (b) permeabilization and (c) staining (or labeling) of intracellular molecules of interest by probes that are readily detectable by flow cytometric techniques, all without any intervening cell-washing (and re-suspension) steps. Rather, the single cell-washing step is effected after these three steps have been carried out. Preferably, the washing step is carried out by passing the fixed, permeabilized and stained cell sample through a semi-permeable membrane that serves to filter out (by transmission) interferants to waste while retaining the cells of interest.

Abstract: Described are compositions with tethered growth effector molecules, and methods of using these compositions for growing cells and tissues. Growth effector molecules, including growth factors and extracellular matrix molecules, are flexibly tethered to a solid substrate. The compositions can be used either in vitro or in vivo to grow cells and tissues. By tethering the growth factors, they will not diffuse away from the desired location. By making the attachment flexible, the growth effector molecules can more naturally bind to cell surface receptors. A significant feature of these compositions and methods is that they enhance the biological response to the growth factors. The method also offers other advantages over the traditional methods, in which growth factors are delivered in soluble form: (1) the growth factor is localized to a desired target cell population; (2) significantly less growth factor is needed to exert a biologic response.

Abstract: The invention concerns a process for producing a three-dimensional bioartificial tissue having viable cells in or on a matrix, and by which cells and matrix can be cultivated into a tissue or a precursor of a tissue, a vascularized tissue of biological materials, obtained by this process, and an experimental reactor for scientific purposes and for producing clinically usable tissues and organs.

Abstract: A method for obtaining lineage committed human cells imbued with enhanced proliferative potential, biological function, or both, comprising culturing lineage committed human cells under physiologically acceptable liquid culture conditions, where the liquid culture medium is replaced at a rate and for a time sufficient to obtain the human lineage committed cells imbued with enhanced proliferative potential, biological function, or both; and isolating the cultured cells.

Abstract: A method and structure for growing living organic tissue in which a scaffold is provided on which cells of the tissue may be seeded and on which the tissue may be grown and a plurality of membrane capillaries are provided for conveying a nutrient fluid, the plurality of membrane capillaries being interspersed through the scaffold and having membranes which are permeable to nutrients and oxygen such that the tissue may be grown throughout the scaffold and whereby upon in vivo implantation a supporting nutrient tissue supply rapidly establishes.

Abstract: This invention provides for a pharmaceutical or veterinary paste formulation comprising: an effective amount of a therapeutic agent; fumed silica; a viscosity modifier; a hydrophilic carrier; optionally, an absorbent; and optionally, a colorant, stabilizer, surfactant, or preservative. This invention also provides for methods of using these formulations for treating various disease states as well.

Abstract: The present invention relates to a reactor module constructed of hollow fibers and cells as well as to reactors comprising this reactor module.

Abstract: A cell culture unit is disclosed herewith comprising a shell having two ends with an elongated chamber there between. A liquid and a gas perfusion port are located on each end. Liquid perfusion fibers are connected to the liquid perfusion ports and gas perfusion fibers are connected to the gas perfusion ports. These fibers thereby define an extracapillary and intracapillary space. The cell culture unit further comprises means for communicating with the intracapillary space of the gas perfusion fibers means for communicating with the intracapillary space of the liquid perfusion fibers, and means for communicating with the extracapillary space.

Abstract: A cell and tissue culture modeling device comprising a housing having an interior chamber, an inlet port in fluid communication with the internal chamber, an outlet port in fluid communication with the internal chamber, a plurality of hollow fibers disposed within the interior chamber and traversing the length of the housing between the inlet port and the outlet port. Each of the plurality of hollow fibers has an interior defining an intracapillary space and the interior chamber defines an extracapillary space unoccupied by the plurality of hollow fibers. To access the extracapillary space of the device, a portion of the housing is removable. The device can be used to conduct permeability, drug efficacy, and gene expression studies.

Abstract: A method for treating systemic inflammatory response syndrome (SIRS) by contacting the bodily fluid of a patient with renal tubule cells outside of the kidney.

Abstract: A bi-component microporous hollow fiber membrane structure is provided for in vivo propagation of cells and use in testing of the effect of medical treatments on cells within the structure. The structure has an inner structure fabricated from a first bio-compatible polymer and an outer structure fabricated from a different polymer that has a lower tendency for cell adhesion than the inner structure polymer. In this way, the inner structure can be selected to optimize cell propagation and the outer structure can be fabricated from a polymer which optimizes the removal of the bi-component structure from its implanted location. The inner and outer structures may have a pore size between 10 and 1000 Angstroms and 100 and 2000 Angstroms, respectively, and be formed from polysulfone or polyether sulfone and polyvinyledene difuoride, respectively. The membrane structure can form macrocapsules containing media and living cells for implanting.

Abstract: A cell and tissue culture modeling device comprising a housing having an interior chamber, an inlet port in fluid communication with the internal chamber, an outlet port in fluid communication with the internal chamber, a plurality of hollow fibers disposed within the interior chamber and traversing the length of the housing between the inlet port and the outlet port. Each of the plurality of hollow fibers has an interior defining an intracapillary space and the interior chamber defines an extracapillary space unoccupied by the plurality of hollow fibers. To access the extracapillary space of the device, a portion of the housing is removable. The device can be used to conduct permeability, drug efficacy, and gene expression studies.

Abstract: The present invention provides novel isothermal, single primer linear nucleic acid amplification methods. Methods for amplifying complementary DNA using a composite primer, primer extension, strand displacement, and optionally a termination sequence, are provided. Methods for amplifying sense RNA using a composite primer, primer extension, strand displacement, optionally template switching, a propromoter oligonucleotide and transcription are also provided. The invention further provides compositions and kits for practicing said methods, as well as methods which use the amplification products.

Abstract: A bioreactor having an outer shell compartment containing many coaxial pairs of hollow microporous fibers. An annular compartment exists between an outer surface of the inner hollow microporous fiver and the inner surface of the outer hollow microporous fiber. The annular compartment preferably contains blood or plasma. The blood or plasma is, thus, exposed to two microporous hollow fibers which have fluids which can purify or otherwise affect the blood through the walls of two different microporous hollow fibers. An artificial liver or kidney can result when liver or kidney cells are placed in the shell compartment.

Abstract: The present invention provides cell compositions for in vivo implantation, and designed for the sustained and controlled delivery of therapeutic substances.

Abstract: The invention relates to the use of microscopic nematodes such as C. elegans in functional high throughput in vivo assays suitable for the detection of inhibitors or activators of intestinal lipid uptake.