A recipient for cell cultivation having an inner compartment adapted for cell growth, in one embodiment, an outer tubular wall extends in a longitudinal direction and delimits an outer boundary of the inner compartment in a radial direction. First and second ends delimit the inner compartment at the first respectively the second outer end of the outer tubular wall. A fixed packing in the inner compartment comprises a packing, such as a fiber matrix. Additional embodiments and related methods are also disclosed.

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 bioreactor system for culturing cells is provided. The system includes a cell culture vessel with an interior reservoir. an inlet and an outlet fluidly connected to the reservoir. A fluid flow path supplies fluid to the inlet and receives fluid from the outlet. and a media conditioning vessel is fluidly connected to the cell culture vessel. The system also includes an outlet sensor arranged at the outlet of the cell culture vessel. The outlet sensor can detect a property of cell culture media exiting the cell culture vessel via the outlet, and the bioreactor system can adjust a property of the cell culture media based on the property detected by the outlet sensor.

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 fixed-bed bioreactor system (300) is provided that includes a vessel with a media inlet (310), a media outlet (312), and an interior cavity disposed between and in fluid communication with the media inlet and media outlet; 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 having a plurality of porous disks (308) in a stacked arrangement; and a harvesting volume (2010,2020) to hold a fluid, the harvesting volume being in fluid communication with the interior cavity, wherein each of the plurality of porous disks comprises a surface configured to culture cells thereon. The harvesting volume can be inside or outside of the vessel.

The invention relates to a device and a method for compressing a hydrogel layer (H), wherein a separate piston (600) that is designed to be connected to a second component (400) of the device in a releasable manner in an operating mode of the device, particularly by means of a latching connection, presses along a compression direction (C) against said hydrogel layer (H) residing on a membrane bottom (501) of a graft frame (500) so as to compress the hydrogel layer (H) between the piston (600) and the membrane bottom (501).

We have modified a commercially-available adherent cell culture bioreactor in several ways to increase productivity of cultured cells, while decreasing contamination risk. We found that modifying a commercially-available adherent cell culture bioreactor to provide for slower cell culture medium flow unexpectedly and dramatically increases the productivity of the cultured adherent cells. We also developed a new sampling manifold configuration and new way of taking samples, to reduce contamination risk.

Systems and methods for harvesting cells include a bioreactor with a structure for cell entrapment/adherence and growth, such as a fixed bed structure. A cell harvest mechanism is adapted to agitate the bioreactor, such as by vibrating or shaking the fixed bed, and to move a liquid level relative to the structure, such as by repeatedly flushing and filling the bioreactor. A cell detaching solution is provided to the bioreactor, such as an enzymatic cocktail for the detachment of cells without producing clumps or aggregates. The bioreactor may comprise a preculture vessel upstream of another bioreactor.

A fixed-bed cell culture matrix formed from a rolled cell culture substrate is provided that includes a cell culture vessel having an inlet, an outlet, and an interior reservoir fluidly disposed in a fluid pathway between the inlet and the outlet. A cell culture matrix is disposed in the reservoir in a wound configuration around a winding axis. The cell culture matrix includes a structurally defined substrate from a substrate material defining a plurality of pores, the substrate material being designed for adhering cells thereto. A plurality of permeability zones are provided in the cell culture matrix, which include an opening in the substrate, where the opening being larger than a diameter of any of the plurality of pores. The plurality of permeability zones are arranged with a variable periodicity along a length of the substrate in the wound configuration.

The present invention relates to an apparatus and a method for fermenting, separating, and refining a product, which is produced by cultivating a microorganism. The apparatus and the method for fermenting, separating, and refining, of the present invention, can separate and refine the product that is produced by microbial fermentation in a simple, continuous manner and with high efficiency.