A bioreactor for culturing of cells is described. Screens suitable as a cell growth scaffold may comprise crossed fibers. Screens may be contained loosely in a screen holder, which in turn may be contained inside a manifold assembly. A lower manifold, screen holder and upper manifold may have identical or similar interior open cross-sections. Flow of liquid medium can occur upwardly through the array of screens, then flowing over a weir in the presence of an air pocket, and into a moat and a pump. The screen holder may have slots whose exterior-facing ligaments are rounded, and may have grooves whose interior-facing edges are rounded. These components may be located inside an incubator suitable to maintain desired environmental conditions and cleanliness.

An in vitro microfluidic intestine on-chip is described herein that mimics the structure and at least one function of specific areas of the gastrointestinal system in vivo. In particular, a multicellular, layered, microfluidic intestinal cell culture, which is some embodiments is derived from patient's enteroids-derived cells, is described comprising L cells, allowing for interactions between L cells and gastrointestinal epithelial cells, endothelial cells and immune cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal autoimmune tissue, e.g., diabetes, obesity, intestinal insufficiency and other inflammatory gastrointestinal disorders. These multicellular-layered microfluidic intestine on-chips further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal duodenum, small intestinal jejunum, small intestinal ileum, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic gut-on-chips allow identification of cells and cellular derived factors driving disease states and drug testing for reducing inflammation.

A process and system for efficiently producing reference data that can be fed into a predictive model for predicting quality attribute concentrations in cell culture processes. A perfusion bioreactor is operated at pseudo-steady-state conditions and one or more attribute influencing parameters are manipulated and changed over time. As the one or more attribute influencing parameters are manipulated, one or more quality attributes are monitored and measured. In one embodiment, multiple quality attributes are monitored and measured in parallel. The quality attribute information is recorded in conjunction with the changes in the attribute influencing parameters. This information is then fed to the predictive model for propagating cell cultures in commercial processes and maintaining the cell cultures within desired preset limits.

Described are embodiments for expanding cells in a bioreactor. In one embodiment, methods are provided that distribute cells throughout the bioreactor and attach cells to specific portions of a bioreactor to improve the expansion of the cells in the bioreactor. Embodiments may be implemented on a cell expansion system configured to load, distribute, attach and expand cells.

A reversible liquid filtration system for cell culture perfusion comprises: a bioreactor vessel (B4), for storing the cell culture (L4); a perfusion pump (P7), comprising a reciprocable element (P71) which is movable in opposing first and second pumping directions (dF, dR); a filter (F4); and first and second bi-directional valves (BV1, BV2), each selectively controllable between open and closed positions. The perfusion pump (P7), the filter (F4), and the first and second bi-directional valves (BV1, BV2), together comprise a fluidic circuit in communication with the bioreactor vessel (B4). The bi-directional valves (BV1, BV2) are controllable to open and close in co-ordination with the reciprocating perfusion pump (P7), in order to enable both a two-way filtering flow around the fluidic circuit and also an alternating filtering flow between the bioreactor vessel (B4) and the perfusion pump (P7).

Disclosed herein are compositions and methods to decellularize an isolated organ or portion thereof. Also disclosed herein are compositions and methods for treatment of disease utilizing a decellularized or recellularized organ. Also disclosed herein are methods of improving decellularization and/or recellularization of an isolated organ or portion thereof.

A cell culture microdevice for maintaining and culturing a cell therein comprising a cell culture unit having at least a first cell carrier unit defining a cell culture chamber formed therein, the first cell carrier unit formed from at least, a chamber base shaped to support the cell thereon, and one or more chamber walls having one or more chamber wall surfaces enclosing the cell culture chamber about a chamber boundary, the first cell carrier unit further providing a guiding surface to guide instruments or fluids into the cell culture chamber located at an aperture through a chamber wall, wherein the cell culture microdevice is configured at a scale to substantially enclose a single cell or cell mass therein. Embodiments of the cell culture microdevice may be suitable for in vitro fertilisation procedures and drug efficacy testing.

Embodiments of the present disclosure relate generally to systems and methods for perfusion cell culture involving alternating fluid flows between first and second flexible vessels. For example, a hollow fiber filter module may be attached to first and second culture vessels which each include inner and outer vessels. A pressure source may cause a pressure differential between the outer vessels, which may cause a responsive fluid flow between the inner vessels across a hollow fiber filtration unit.

Embodiments described herein generally provide for expanding cells in a cell expansion system. The cells may be grown in a bioreactor, and the cells may be activated by an activator (e.g., a soluble activator complex). Nutrient and gas exchange capabilities of a closed, automated cell expansion system may allow cells to be seeded at reduced cell seeding densities, for example. Parameters of the cell growth environment may be manipulated to load the cells into a particular position in the bioreactor for the efficient exchange of nutrients and gases. System parameters may be adjusted to shear any cell colonies that may form during the expansion phase. Metabolic concentrations may be controlled to improve cell growth and viability. Cell residence in the bioreactor may be controlled. In embodiments, the cells may include T cells. In further embodiments, the cells may include T cell subpopulations, including regulatory T cells (Tregs), for example.

The invention generally relates to a microfluidic platforms or “chips” for testing and conducting experiments on the International Space Station (ISS). More specifically, microfluidic Brain-On-Chip, comprising neuronal and vascular endothelial cells, will be analyzed in both healthy and inflamed states to assess how the circumstances of space travel affect the human brain.