Exemplary embodiments describe apparatuses and related processes for improving mixing and sheer in a fixed film reactor. One process can include recycling at least a portion of a biogas product through at least one sparger below a fixed film zone in the fixed film reactor at conditions sufficient for mixing and sheering the film from an internal structure within the fixed film zone. Often, a cross-sectional area of the fixed film zone fills at least about 90% of a cross-sectional area of the fixed film reactor.

A macrocarrier for the propagation of biological cells is described. The macrocarrier comprises substrate particles that are coated with a thermoresponsive polymer, which is capable of providing the macrocarrier with a cell-receiving surface and responding to a change in temperature to release cells from the macrocarrier. At least 50% of the substrate particles have a particle size of at least 1 mm. A system for the propagation of biological cells and a process for the propagation of biological cells are also described.

An apparatus is provided for bioprocessing, such as for culturing cells. The apparatus includes a bioreactor with a chamber having cells and a chamber for) temperature regulation of the cells. In some embodiments, a freezer is connected to the bioreactor for freezing the cells in the chamber, and a heater may also be provided for actively thawing the cells. Related methods are also disclosed.

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 bio reactor. 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 beds 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.

The present invention relates to improved methods for producing biosynthetic products in a cascade of bioreactors. In particular the present invention relates to methods and a cascade of bioreactor systems comprising at least two bioreactors and at least one concentration unit.

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.

The present invention pertains to an economic packed-bed perfusion system for the production of pharmaceutical grade of recombinant TNK-tPA. The present invention involves a cell culture process utilizing CHO cells more specifically in a micro/macro carriers based packed-bed perfusion system. The process of the present invention results in optimum cell growth and maintenance, and minimal build-up of toxic by-products such as lactate and ammonia. The system of the present invention discloses optimized process parameters to enable a resultant TNK-tPA with high yield and pharmaceutical grade purity. The process of the present invention is industrially applicable and possesses economy of scale.

A sampler for use with a bioreactor for growing a cell culture is disclosed. In one embodiment, the bioreactor includes a structured fixed bed including a removable sample portion for recovering a sample of cells from the cell culture. Related apparatuses and methods are also disclosed.

A fixed-bed bioreactor system for culturing cells is provided. The system includes a plurality of cell culture subunits, each cell culture subunit including a distribution plate with a major surface to support a cell culture substrate, an inlet, and a plurality of outlets disposed on the major surface and in fluid communication with the inlet. The subunit also includes a cell culture substrate disposed on the major surface of the distribution plate. The system further includes a plurality of input lines for supplying at least one of cells, cell culture media, nutrients, and reagents to the plurality of cell culture subunits, each input line of the plurality of input lines being fluidly connected to the inlet. The plurality of outlets is configured to distribute at least one of cells, cell culture media, nutrients, and reagents from the plurality of input lines substantially uniformly across the cell culture substrate.