The subject invention provides methods and systems for producing microbe-based compositions that can be used in the oil and gas industry, environmental cleanup, agriculture, and many other applications. More specifically, the subject invention provides methods and systems for producing microorganisms and/or growth by-products thereof using a hybrid solid state-submerged fermentation method, wherein a matrix comprised of a solid material covered in an alginate coating is formed inside a liquid fermentation vessel. In some embodiments, the solid material is a plurality of natural loofa sponges.

A fixed-bed bioreactor system is provided that includes a vessel with a media inlet, a media outlet, and an interior cavity disposed between and in fluid communication with the media inlet and media outlet. The vessel further includes a cell culture substrate disposed in the interior cavity between the media inlet and the media outlet in a packed-bed configuration, the cell culture substrate including a plurality of porous disks in a stacked arrangement. The interior cavity includes a cell culture section and a spacer section, the cell culture substrate defining the cell culture section and the spacer section being disposed between the cell culture section and the media outlet, and each of the plurality of porous disks has a surface configured to culture cells thereon.

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.

A cell culturing container including a fixed bed is provided for forming a bioreactor (100). In one version, a container in the form of a tubular body is formed by first and second interlocking portions (115a, 115b). The container forms a compartment for receiving the fixed bed (122) for culturing cells, which container may be removably inserted into an inner compartment of the bioreactor so as form an outer chamber for circulating fluid to or from the fixed bed. The container may also include a removable base (130) for receiving an agitator (118) for agitating and thus circulating the fluid. Related methods are also disclosed.

There is provided a bioreactor including: a chamber unit having an accommodating space therein; an upper fixing member and a lower fixing member that are disposed at respective planes perpendicular to a central axis of the chamber unit inside the chamber unit and are movable in a central-axis direction of the chamber unit; and a filling layer that is formed in a space between the upper fixing member and the lower fixing member inside the chamber unit and contains a plurality of carriers.

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.

We have found a way to make possible large-scale plasmid transfection using PEI to produce high titer viral vectors in fixed bed or adherent cell culture bioreactors by using PEI as a transfection agent, while avoiding formation of the PEI-plasmid precipitate which in prior art approaches clogged adherent bioreactor substrates. We have also found a way to improve PEI-based transfection by modifying how pH and CO.sub.2 are managed during transfection.

A cell culture tool configured to be produced in a simple facility to obtain a cell mass having a desired shape. The cell culture tool includes a cell culture base layer that contains a cell culture base. The cell culture base layer has a cell adhesive area to which a cell is adherable and a cell adhesion inhibitory area where cell adhesion is inhibited. The cell adhesion inhibitory area includes a modified product of the cell culture base.

A cell culture device comprising a fixed bed arranged in a housing, the fixed bed comprising a continuous pleated porous medium comprising a top end, a bottom end, a front side, a rear side, a right side, and a left side, and a plurality of pleats folded on the right side and the left side, and having vertical fluid flow channels along the longitudinal axis between adjacent pleats, is disclosed.

A packed bed bioreactor is fabricated as a monolith entirely using additive manufacturing techniques, also known as 3D printing. Construction of a bioreactor in this manner enables control over the reactor dimensions and properties (such as void volume) as well as the dimensions, shape, and pattern of the media bed. Together these attributes give the end-user control over the size, shape, material, and flow characteristics of the bioreactor.