An apparatus and method for the delivery and deposition of particles air-liquid-interface (ALI) cell cultures includes a sample inlet coupled to a growth tube having interior walls that are wet. The growth tube is configured to operate at a first temperature along a first length of the tube and a second temperature along a second length positioned between the first length and a growth tube outlet. The apparatus also includes a nozzle plate having a plurality of nozzles. The exposure chamber adapted to hold cell cultures at an air-liquid interface positioned underneath the plurality of nozzles and a temperature regulator adapted to control a temperature of the exposure chamber. The apparatus also includes a controller including instructions operable to cause the controller to maintain a relative humidity within the exposure chamber by controlling at least the second temperature of the growth tube and the temperature of the exposure chamber.

A method of making a flowable, dried agglomerated nutrient medium is provided. The method comprises introducing a nutrient component comprising a powdered nutrient, and an agglomeration liquid, into an agglomerator comprising a flow-through-type agglomeration chamber, wet-massing the nutrient component with the agglomeration liquid in the agglomeration chamber for a predetermined period of time to form agglomerated nutrient medium particles, and exposing the agglomerated nutrient medium particles to drying conditions for a period of time to form the dried, agglomerated nutrient medium. The nutrient component facilitates the growth of a microorganism. Compositions, articles, and kits comprising the flowable, dried agglomerated nutrient medium are also provided.

Processes for culturing mammalian cells, and for producing recombinant products expressed by mammalian cells, involving a pH up-shift are provided. The processes are particularly suitable for industrial-scale cell culture, and for culture of cells that produce therapeutic products. The processes comprise a first culture stage, carried out at a first pH, and a second culture stage, carried out at a second pH that is higher than the first pH.

Herein is reported a feed mixing device for adding feed solutions with a non-physiologically pH value to a cell cultivation vessel comprising a chamber for mixing the feed solutions prior to their addition to the cell cultivation vessel as well as its use. With the feed mixing device as reported herein feed components can be provided in solution at a pH value at which they have good solubility and/or good stability whereby the pH value can be clearly different from the pH value of the cultivation medium, i.e. different from the physiological pH value. This allows performing the cultivation with more flexibility compared to a cultivation in which the pH value of the feed solution is limited to a small range around the pH value of the cultivation.

The present invention relates to methods of modulating (e.g., reducing) the mannose content, particularly high-mannose content of recombinant glycoproteins.

Systems and methods (S/M) to detect stress in stem cells are described. The S/M, including modified stem cells, assays and high throughput screens, can be used to identify compounds or other potential stressors that can negatively affect development potential.

The present invention is directed generally to dry cell culture media or feeds in pellet formats which can be reconstituted into liquid media for culturing cells in vitro. Each pellet composition may comprise the same or a different composition; for example, different vitamins, amino acids, buffers, trace salts, pH, iron chelators, etc. The invention also relates to methods of making dry cell culture media by altering ratios of different pellet compositions, or, methods of making modular dry cell culture media, or customizing media formulations for growing a cell type using pellets. According to the invention, media pellets may be easier to handle either before reconstitution, during shipping and handling; and/or during reconstitution. Media pellets may be used in any container like bags including sterile, single use bags for preparing media formulations. The invention also relates to kits and culture systems using media pellets.

The present invention relates to a chemically defined medium for eukaryotic cell culture, comprising water, at least one carbon source, one or more vitamins, one or more salts, one or more fatty acids, one or more buffer components, selenium, at least one substance of the group of Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) and at least one polypeptide of the GF- superfamily with the ability to inhibit stem cell differentiation, its use in the culture of human pluripotent stem cells, a cell culture system comprising human pluripotent stem cells and the chemically defined medium, as well as a kit for proliferation and/or maintenance of human pluripotent stem cells.

Methods and compositions are provided for generating targeted genetic modifications on the Y chromosome or a challenging target locus. Compositions include an in vitro culture comprising an XY pluripotent and/or totipotent animal cell (i.e., XY ES cells or XY iPS cells) having a modification that decreases the level and/or activity of an Sry protein; and, culturing these cells in a medium that promotes development of XY F0 fertile females. Such compositions find use in various methods for making a fertile female XY non-human mammal in an F0 generation.

The present invention pertains to a method for the generation of neurotoxin-sensitive, neuronal differentiated cells comprising the steps of: a) cultivating tumor cells which are able to differentiate into neuronal cells in a culture medium under conditions and for a time which primes said tumor cells for neuronal differentiation; and b) cultivating the tumor cells primed for neuronal differentiation of a) in a differentiation medium having an osmolality of 100 to 270 mOsm/kg, and comprising (i) B27 supplement and/or (ii) N2 supplement, for at least 3 days, thereby obtaining neurotoxin-sensitive, neuronal differentiated cells. The invention further relates to neurotoxin-sensitive, neuronal differentiated cells obtainable by the method of the invention. In addition, the invention encompasses a method for determining the activity of a neurotoxin polypeptide comprising the steps of: a) contacting the neurotoxin-sensitive, neuronal differentiated cells obtainable by the method of the invention with a neurotoxin polypeptide; b) cultivating the neurotoxin-sensitive, neuronal differentiated cells of step a) for 3 to 74 hours or 72 hours under conditions which allow for the neurotoxin polypeptide to exert its biological activity; and c) determining the activity of the neurotoxin polypeptide in the said cells after cultivation according to step b). Finally, the invention provides for a medium comprising OptiMEM, FBS, B27 supplement, and N2 supplement.