Abstract: An apparatus and method to maintain pH within a range conducive for cell growth in a bicarbonate-containing cell culture system without the addition of base. The method relies on the gas transfer characteristics of the bioreactor system to modulate the CO2 transfer to and from the cell culture such that the pH of the cell culture can be maintained within a desired range.

Abstract: Described are embodiments for expanding cells in a bioreactor. In one embodiment, methods are provided that distribute cells throughout the bioreactor and attach cells to specific portions of a bioreactor to improve the expansion of the cells in the bioreactor. Embodiments may be implemented on a cell expansion system configured to load, distribute, attach and expand cells.

Abstract: A stem cell production system provided with a preintroduction cell-feeding solution channel 20 through which a solution containing cells passes, an induction factor-feeding solution mechanism 21 for feeding a pluripotency induction factor to the preintroduction cell-feeding solution channel 20, a factor introduction device 30 connected to the preintroduction cell-feeding solution channel 20 for making cells with induction factor introduced by introducing the pluripotency induction factor into the cells, a cell mass-making device 40 for making multiple cell masses comprising stem cells by culturing the cells with induction factor introduced, and a packaging device 100 for sequentially packaging each of the multiple cell masses.

Abstract: A method for treating a flexible plastic substrate is provided herein. The method includes establishing an atmospheric pressure plasma beam from an inert gas using a power of greater than about 90W, directing the plasma beam toward a surface of the flexible polymer substrate, and scanning the plasma beam across the surface of the polymer substrate to form a treated substrate surface.

Abstract: Embodiments described herein generally relate to passively replacing media in a closed cell expansion system to reduce or prevent the dilution of chemical signaling used to inhibit signaling pathways that keep a cell population in the lag phase of cell growth. To prevent such dilution, active inlet fluid flow to the system may be halted. To replace fluid lost by the system, a bag containing media may be attached to the waste line in replacement of the waste or outlet bag connected thereto. By turning off one or more pumps, media from the replacement bag is added to the system at the rate of evaporation. Chemical signaling dilution may be prevented while conserving system resources. Enhancement of chemical signaling to reduce the lag phase of cell growth may further be accomplished by adding molecules, such as chemical-signaling proteins, from a direct source to the system.

Abstract: The present invention pertains to a method for the mass cultivation of cells, and a cell cultivation device and kit. The present invention further pertains to a continuous cell cultivation method and a continuous cell cultivation device in which a carrier is used.

Abstract: A carrier for growing stem cells is provided, the carrier comprises a substrate comprising one or more outer surfaces; and a hydrophilic, water soluble coating material disposed and dried on one or more of the outer surfaces. The carrier comprises one or more structured indentations on one or more of the outer surfaces, wherein the carrier has a length at least about 0.2 mm, a width at least about 0.2 mm, and a height in a range from about 0.05 mm to 1.2 mm and each of the structured indentations has a major axis in a range from about 0.1 mm to 0.5 mm, a minor axis in a range from about 0.1 mm to 0.5 mm and a depth in a range from about 0.025 mm to about 0.5 mm. A method of culturing stem cells and stromal cells using the same carrier are also provided.

Abstract: Described are embodiments for expanding cells in a bioreactor. In one embodiment, methods are provided that distribute cells throughout the bioreactor and attach cells to specific portions of a bioreactor to improve the expansion of the cells in the bioreactor. Embodiments may be implemented on a cell expansion system configured to load, distribute, attach and expand cells.

Abstract: A carrier for expansion of induced pluripotent stem cells is provided, wherein the carrier comprises a substrate comprising one or more outer surfaces, wherein the one or more outer surfaces are modified with gas plasma treatment, and one or more structured indentations on one or more of the outer surfaces. The carrier has a length at least about 0.2 mm, a width at least about 0.2 mm, and a height in a range from about 0.05 mm to 1.2 mm and each of the structured indentations has a major axis in a range from about 0.1 mm to 0.5 mm, a minor axis in a range from about 0.1 mm to 0.5 mm and a depth in a range from about 0.025 mm to about 0.5 mm. A method of making the carrier, and culturing induced pluripotent stem cells using the same carrier are also provided.

Abstract: A carrier for expansion of pluripotent stem cells is provided, wherein the carrier comprises a substrate comprising one or more outer surfaces, wherein the one or more outer surfaces are modified with gas plasma treatment, and one or more structured indentations on one or more of the outer surfaces. The carrier has a length at least about 0.2 mm, a width at least about 0.2 mm, and a height in a range from about 0.05 mm to 1.2 mm and each of the structured indentations has a major axis in a range from about 0.1 mm to 0.5 mm, a minor axis in a range from about 0.1 mm to 0.5 mm and a depth in a range from about 0.025 mm to about 0.5 mm. A method of making the carrier, and culturing stromal cells using the same carrier are also provided.

Abstract: A method of culturing adherent cells is provided, wherein the method comprises providing a carrier for growing the cells, comprising one or more surfaces; and one or more relief features/indentations are present on one or more of the surfaces, wherein the carrier has a length at least about 0.2 mm, a width at least about 0.2 mm, and a height in a range from about 0.012 mm to 0.5 mm; and wherein each of the relief features/indentations has a height above the surfaces in a range from about 2 to 200 ?m, and width in a range from about 20 to 200 ?m; seeding the cells on the carriers; and growing the cells on the carrier.

Abstract: Pressurized hermetically sealed bags disposed inside a cylindrical support and containing a septum with variable density of porosity and dividing the bag into two chambers are used to provide optimal mixing and gasification of nutrient media to grow a variety of biological cultures, particularly the cell cultures to produce a multitude of pharmaceutical and biotechnology products in a disposable system.

Abstract: A large scale cell harvesting method for a pack-bed culture device by providing cell growing space that is packed with a plurality of porous matrices and/or matrix means. When a cell detaching step at least comprising shaking or spinning the culture chamber is performed, the unoccupied space is large enough for the porous matrices collide to each other or to the culture chamber to generate momentum whereby the cells detach from the porous matrices to harvest the cells.

Abstract: A flexible disposable bioreactor having three, stagger-baffled compartments wherein the middle compartment houses a sparging rod is described to provide the highest degree of sparging and mixing to produce biological products.

Abstract: One or more embodiments are described directed to a method and system for loading and distributing cells in a bioreactor of a cell expansion system. Accordingly, embodiments include methods and systems that may provide for adding a plurality of cells to a fluid within a bioreactor of the cell expansion system. A first percentage of the plurality of cells is allowed to settle in the bioreactor and a second percentage of the plurality of cells is allowed to settle outside of the bioreactor. The first percentage of cells is then expanded in the bioreactor. The second percentage of cells is wasted.

Abstract: The present invention is generally in the field of continuous and high-cell-density cultivation in laboratory- or large-scale liquid shaken cultures. More particularly it relates to a method of enzyme-based fed-batch (EnBase) for liquid microbial prokaryotic or eukaryotic cell cultivation having the possibility to manipulate the growth rate of the cultured organisms by a controlled enzymatic release of the growth-limiting substrate-monomer from substrate-polymers or substrate-oligomers.

Abstract: A method and system for achieving a gas-liquid mass transfer includes delivering into a compartment of a container a liquid, the liquid having an exposed top surface disposed within the compartment. A stream of a gas is passed over the top surface of the liquid so that the stream of gas produces turbulence on the top surface that is sufficient to achieve the gas-liquid mass transfer. In one embodiment the liquid is a culture that includes cells or microorganisms and the mass transfer functions to oxygenate the culture sufficient to sustain the cells or microorganisms.

Abstract: The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions.

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: An apparatus for cultivating cells utilizing wave motion comprising a container, a retaining member configured to retain the container, a drive assembly for swiveling the container with respect to the substantially horizontal pivot axis and to swivel, such that during swiveling the pivot axis follows a cyclical closed-loop path.

Abstract: A system and method for rotating a cell growth chamber of a cell expansion system includes a rotatable member for engaging a chamber coupling attached to the cell growth chamber. The rotatable member includes an independently operable mechanism for engaging a rotatable fitting associated with the chamber coupling. In at least one embodiment, the chamber coupling is selectively rotatable by turning the rotatable member, thereby rotating the cell growth chamber around a first axis. The cell growth chamber is also selectively rotatable around a second axis by turning the rotatable fitting associated with the chamber coupling. Other novel aspects include a way of attaching the cell growth chamber to the shaft assembly, and a new tube routing clip.

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: This invention provides a culture control method and a cell culture apparatus that enable stable cell culture by regulating shear stress to be applied to cells within an adequate range. With the application of such culture control method and cell culture apparatus, cell culture is performed under agitation culture conditions in which the shear stress distribution is 0.5 Pa to 20 Pa in 80% or more of the culture vessel by volume.

Abstract: Provided herein are improved methods of culturing a mammalian cell in a conical container, and methods that utilize these culturing methods.

Abstract: A method of mixing a fluid includes positioning a flexible bag into the chamber of a support housing, the support housing having a plurality of baffles positioned so that the bag folds around the baffles. A fluid is delivered into a compartment of the flexible bag. A mixing element, such as an impeller, is moved within the compartment of the flexible bag so as to mix the fluid therein.

Abstract: The invention relates to a process for the culturing of cells by continuous perfusion culturing of a cell culture comprising cell culture medium and cells, wherein cell culture medium is added to the cell culture, the cell culture is circulated over a filter module comprising hollow fibers resulting in an outflow of liquid having a lower cell density than the cell culture and the flow within the filter module is an alternating tangential flow. Preferably, culture medium is added at a particular perfusion rate and/or biomass is removed form the culture at least once. The method is especially suitable for the culturing of aggregating cells. The invention also relates to such a process wherein a biological substance, preferably an antibody, is produced by the cells, which biological substance may be further purified in downstream processing.

Abstract: The invention relates to a reactor driven in an oscillatory-rotary manner about its fixed, preferably vertical, axis, for preferably biotechnological and pharmaceutical applications. By means of its process-intensifying properties for mixing, suspension, gaseous material transport, heat transfer, irradiation and particle retention, the applicability on the industrial scale is ensured. The reactor which succeeds without a shaft seal permits particularly robust production with respect to sterile technique with avoidance of cleaning and cleaning validation required when the reactor is constructed as a single-use reactor.

Abstract: One or more embodiments are described directed to a method and system for loading and distributing cells in a bioreactor of a cell expansion system. Accordingly, embodiments include methods and systems that may provide for adding a plurality of cells to a fluid within a bioreactor of the cell expansion system. A first percentage of the plurality of cells is avowed to settle in the bioreactor and a second percentage of the plurality of cells is allowed to settle outside of the bioreactor. The first percentage of cells is then expanded in the bioreactor. The second percentage of cells is wasted.

Abstract: The present invention provides a vehicle for delivering various chemicals, compositions and proteins to stem cells and embryoid bodies. The vehicle may be biocompatible and biodegradable polymer microparticles. Typically the particles will contain at least a growth factor for delivery to the embryoid bodies, and generally the growth factor induces differentiation of the cells in the embryoid body along a specific lineage. The present invention also provides methods for directing differentiation of the cells in the embryoid body.

Abstract: An inflatable bioreactor bag for cell cultivation, which comprising a top and a bottom sheet of flexible material, joined together to form two end edges and two side edges, wherein one baffle or a plurality of baffles extend from the bottom sheet in a region where the shortest distance to any one of the two end edges is higher than about one fourth of the shortest distance between the two end edges.

Abstract: The presently disclosed subject matter is directed to a polymeric films suitable for use in a wide variety of applications, including (but not limited to) the formation of bioprocessing containers. Particularly, the disclosed films comprise a first barrier layer comprising polyglycolic acid, polyamide, EVOH, and/or an EVOH blend and a second barrier layer comprising EVOH. The dual barrier layers of the film maintain a high gas barrier under a variety of relative humidity conditions. In addition, the disclosed film is biologically inert and free from film surface-modifying additives such that the film does not inhibit the growth of biological cell cultures.

Abstract: Provided herein are methods for culturing cells, tissues or organoid bodies in the presence of a pulsating alternating ionic magnetic resonance field and models comprising a tissue-like assembly of the cells so cultured. The cells, tissues or organoid bodies are introduced into a culture unit comprising growth and nutrient modules in which the gravity vector of the growth unit is continually randomized and cultured in the presence of the alternating ionic magnetic resonance field.

Abstract: The present invention relates generally to the field of cell culture, which is a laboratory process used primarily for the growth, propagation, and production of cells for analysis and the production and harvesting of cell products. The present invention comprises functionalized and/or engineered hydrogel microcarriers that exhibit any or all of the following properties: controllable buoyancy, ferro- or paramagnetism, molecular or fabricated reporting elements, and optical clarity. The microcarriers are used in a bioreactor that employs external forces to control said microcarrier kinetic energy and translational or positional orientation in order to facilitate cell growth and/or cellular analysis. The bioreactor can be part of an automated system that employs any or all of the following; a microcarrier manufacturing method, a monitoring method, a cell culture method, and an analytical method.

Abstract: A system and method for rotating a cell growth chamber of a cell expansion system includes a rotatable member for engaging a chamber coupling attached to the cell growth chamber. The rotatable member includes an independently operable mechanism for engaging a rotatable fitting associated with the chamber coupling. In at least one embodiment, the chamber coupling is selectively rotatable by turning the rotatable member, thereby rotating the cell growth chamber around a first axis. The cell growth chamber is also selectively rotatable around a second axis by turning the rotatable fitting associated with the chamber coupling. Other novel aspects include a way of attaching the cell growth chamber to the shaft assembly, and a new tube routing clip.

Abstract: A system and method for rotating a cell growth chamber of a cell expansion system includes a rotatable member for engaging a chamber coupling attached to the cell growth chamber. The rotatable member includes an independently operable mechanism for engaging a rotatable fitting associated with the chamber coupling. In at least one embodiment, the chamber coupling is selectively rotatable by turning the rotatable member, thereby rotating the cell growth chamber around a first axis. The cell growth chamber is also selectively rotatable around a second axis by turning the rotatable fitting associated with the chamber coupling. Other novel aspects include a way of attaching the cell growth chamber to the shaft assembly, and a new tube routing clip.

Abstract: The present disclosure provides systems and methods of using a semipermeable membrane in a dialysis fermenter as a separation layer between a cell-containing liquid culture medium and a non-cell-containing dialysis medium. In some embodiments, the semipermeable membrane may have a molecular cut-off of 15 kDa to 50 kDa. The instant disclosure also provides a dialysis fermenter with compartments for cell-containing culture medium, non-cell-containing nutrient solution as well as an exchange unit having a semipermeable membrane, wherein mass transfer takes place between the culture medium and the dialysis medium by means of diffusion and/or ultrafiltration. Methods for culturing cells are also disclosed.

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: The invention relates to a process for the culturing of cells by continuous perfusion culturing of a cell culture comprising cell culture medium and cells, wherein cell culture medium is added to the cell culture, the cell culture is circulated over a filter module comprising hollow fibers resulting in an outflow of liquid having a lower cell density than the cell culture and the flow within the filter module is an alternating tangential flow. Preferably, culture medium is added at a particular perfusion rate and/or biomass is removed form the culture at least once. The method is especially suitable for the culturing of aggregating cells. The invention also relates to such a process wherein a biological substance, preferably an antibody, is produced by the cells, which biological substance may be further purified in downstream processing.

Abstract: The invention relates to methods for preparing and performing quantitative PCR analyses, a new sealing device and a new use. According to the invention, a sample vessel containing the samples to be analyzed is sealed by placing a planar sealing device on the vessel to cover the samples and applying pressure on the sealing device in order to deform the sealing device so as to form a light-refracting geometry individually for the samples to be analyzed. The invention offers a convenient way of sealing the vessel and forming analysis-improving optical lenses over the samples simultaneously.

Abstract: Methods for controlling the level of dissolved carbon dioxide and limiting osmolality in a mammalian cell culture process to enhance cell growth, viability and density, and increase biologic product concentration and yield are provided. Such control of the level of dissolved carbon dioxide and pH as well as the resulting ability to limit osmolality in a mammalian cell culture process is achieved by adopting alternative pH control strategies and CO2 stripping techniques during a mammalian cell culture process. Such pH control techniques and carbon dioxide stripping occur without foam and with little or no damage to the mammalian cells.

Abstract: The present invention provides methods and compositions for the propagation and expansion of neural precursor cells (NPCs). NPCs may be used in the clinical implementation of stem cell therapy to treat disorders such as Parkinson's disease, Huntington's disease, neuropathic pain and other diseases of the central nervous system. The large-scale production of NPCs in bioreactors allows for the generation of clinical quantities of these cells.

Abstract: A system for mixing a liquid solution or suspension includes a support housing bounding a compartment and a collapsible bag disposed within the compartment. A mixer is disposed within the collapsible bag while a sparger delivers a gas to the lower end of the collapsible bag. A gas outlet line extends from an upper end of the collapsible bag to a condenser assembly. A gas exhaust line and a fluid collection line both extend from the condenser assembly.

Abstract: The invention relates to a process for reducing the amount of deposits during the culture of organisms, and in particular of cell cultures, where these have a tendency towards agglomeration or adhesion to the bioreactor and to its elements, or where these are readily susceptible to agglomeration or adhesion of cell debris or of substances.

Abstract: The present invention is of a method of dynamically generating human embryoid bodies which can be used for generating lineage specific cells and cell lines. Specifically, the present invention can be used to generate ESC-differentiated cells for cell-replacement therapy.

Abstract: We disclose a particle comprising a matrix coated thereon and having a positive charge, the particle being of a size to allow aggregation of primate or human stem cells attached thereto. The particle may comprise a substantially elongate, cylindrical or rod shaped particle having a longest dimension of between 50 ?m and 400 ?m, such as about 200 ?m. It may have a cross sectional dimension of between 20 ?m and 30 ?m. The particle may comprise a substantially compact or spherical shaped particle having a size of between about 20 ?m and about 120 ?m, for example about 65 ?m. We also disclose a method of propagating primate or human stem cells, the method comprising: providing first and second primate or human stem cells attached to first and second respective particles, allowing the first primate or human stem cell to contact the second primate or human stem cell to form an aggregate of cells and culturing the aggregate to propagate the primate or human stem cells for at least one passage.

Abstract: The present disclosure provides ex vivo-derived mineralized three-dimensional bone constructs. The bone constructs are obtained by culturing osteoblasts under randomized gravity vector conditions. Preferably, the randomized gravity vector conditions are obtained using a low shear stress rotating bioreactor, such as a High Aspect Ratio Vessel (HARV) culture system. The bone constructs of the disclosure have utility in physiological studies of bone formation and bone function, in drug discovery, and in orthopedics.

Abstract: The present invention is of a method of dynamically generating human embryoid bodies which can be used for generating lineage specific cells and cell lines. Specifically, the present invention can be used to generate ESC-differentiated cells for cell-replacement therapy.

Abstract: A bioreactor and a method for growing engineered tissue provide facing surfaces in a vessel for containing cell-culture media. The facing surfaces are equidistant and define a gap therebetween while providing substrates for cell tissue growth. By maintaining conditions within the vessel conducive to cell tissue growth and moving the surfaces relative to one another within such cell culture media, tissue growing thereupon is subjected to physiological flow and shear stress, preferably through the use of oscillating motion, and engineered tissue is produced.

Abstract: A system and method for rotating a cell growth chamber of a cell expansion system includes a rotatable member for engaging a chamber coupling attached to the cell growth chamber. The rotatable member includes an independently operable mechanism for engaging a rotatable fitting associated with the chamber coupling. In at least one embodiment, the chamber coupling is selectively rotatable by turning the rotatable member, thereby rotating the cell growth chamber around a first axis. The cell growth chamber is also selectively rotatable around a second axis by turning the rotatable fitting associated with the chamber coupling. Other novel aspects include a way of attaching the cell growth chamber to the shaft assembly, and a new tube routing clip.

Abstract: Methods for controlling the level of dissolved carbon dioxide and limiting osmolality in a mammalian cell culture process to enhance cell growth, viability and density, and increase biologic product concentration and yield are provided. Such control of the level of dissolved carbon dioxide and pH as well as the resulting ability to limit osmolality in a mammalian cell culture process is achieved by adopting alternative pH control strategies and CO2 stripping techniques during a mammalian cell culture process. Such pH control techniques and carbon dioxide stripping occur without foam and with little or no damage to the mammalian cells.