A modular and stacked cell culture system that includes a standalone cell culture subunit with an interior cavity to house a cell culture substrate in a cell culture space, a fluid inlet to supply fluid to the cell culture space, and a fluid outlet to remove fluid from the cavity. The cavity is arranged for fluid to flow in from the fluid inlet, then through the cell culture space, and then out through the fluid outlet. The subunit further includes an alignment feature on at least one of a top and a bottom of the standalone cell culture subunit, wherein the alignment feature aligns with an alignment feature of another standalone cell culture subunit, such that multiple standalone cell culture subunits are stackable.

The invention relates to a method of increasing the yield of virus, virus particles, or viral vectors from host cells in a bioreactor. The invention provides a reproducible and robust method and system of determining and controlling the optimal time of infection of host cells using a correlation of process air parameters including Air flow, O.sub.2 flow, and respective trends thereof resulting in increased virus yield.

An apparatus for culturing cells with enhanced gas transfer and thermal regulation is provided. The apparatus includes a bioreactor with a cell culture bed, such as a fixed structured bed. A pump, such as an agitator, serves to pump liquid through the cell culture bed, and a container is provided for the agitator. A first conduit may be associated with the container, such as by being connected to it or adjacent an opening into it. The bioreactor may also include flow extenders to enhance the gas transfer to a liquid used as media to culture the cells, as well as optional thermoregulators. Related methods are also disclosed.

A system and method for the production of microbial consortiums and by-product material is provided. A physical containment system comprising phase spaces arranged in a discrete order to favor specific biological reactions is also provided. Phase profiles and phase data sets include the pre-determined physical and biological parameters for the phase space transitions. Movement of material from one phase to the next is hydraulically balanced enabling working fluid to continuously move in a fixed direction and rate of flow. Continuous monitoring of phase profiles and phase data sets provide feedback to the system enabling alteration of the conditions in the system to control reactions therein.

An apparatus for culturing cells includes a bioreactor. The bioreactor may be modular and may include in a chamber a fixed bed, such as an unstructured or structured fixed bed (such as a spiral bed) for culturing cells, with a return column arranged centrally within the chamber. The modular bioreactor may include a plurality of structured fixed bed arranged in a stacked configuration. The modular bioreactor may include an outer casing forming a space for conditioning (e.g., insulating, heating, cooling) at least a chamber in which cells are cultured. The bioreactor may also include an impeller with radially curved blades, and may also suspend the impeller so that it may move from side-to-side and align with an external drive. Related methods are also disclosed.

An active solid state fermentation bioreactor for producing gases, liquid(s) or solids from gaseous or gaseous and liquid starting materials and a fermentation process using the reactor are disclosed, The bioreactor includes three major phases; a solid phase including the porous solid support, a liquid phase comprising liquid, and a gaseous phase. The solid phase includes a porous solid support, in which at least 20% of the pore volumes have a size resulting in a liquid suction of about 0.01 to about 0.1 bars if these pores are filled with liquid, the porous solid support is inoculated with desired micro-organisms, the volume of the gaseous phase is 20% to 60% of the volume of the bioreactor, and the liquid phase is at least 20% of the reactor volume, The unsaturated capillary conductivity of filling/packing solid material of the bioreactor is at least 0.1 cm/ h. The solid state fermentation bioreactor enables a large gas-liquid interface, in which the filling material has a good capillary conductivity despite the unsaturated state.

Described herein is a beads-free bioprocessor as an automated and cost-effective T cell processing and manufacturing platform. T cells are a core component in CAR T cell therapies for cancer treatment, but are difficult to manufacture to scale in clinically relevant quantities. The 3D bioprocessor provides an alternative device that is scalable, beads-free, easy-to-use, and cost-effective for using CAR T cell therapy in cancer immunotherapy. Besides CAR T cell application, this platform technology has potential for many other applications such as cancer cell isolation.

Described herein are compositions, methods, kits, and systems relating to smooth, spherical microgels which can be charge-neutral. The microgels can be made using an emulsification process. In certain aspects, charge-neutral microgels as described herein are suitable for 3D cell culture, use in perfusion bioreactors, and/or 3D printing of cells for 3D cell culture.

A system and method for the production of microbial consortiums and by-product material is provided. A physical containment system comprising phase spaces arranged in a discrete order to favor specific biological reactions is also provided. Phase profiles and phase data sets include the pre-determined physical and biological parameters for the phase space transitions. Movement of material from one phase to the next is hydraulically balanced enabling working fluid to continuously move in a fixed direction and rate of flow. Continuous monitoring of phase profiles and phase data sets provide feedback to the system enabling alteration of the conditions in the system to control reactions therein.

Described herein are genetically-engineered organisms comprising synthetic operons for the production of isoprenoids, carotenoids, and retinoids, optimized for use in a hydrocarbonoclastic organism, and methods for the synthesis and extraction of isoprenoids in a biofilm bioreactor comprising the genetically-engineered organisms.