A cell culture substrate (200, 308) for a fixed bed bioreactor and a fixed bed bioreactor having such a cell culture substrate is provided. The substrate has a structurally defined surface for culturing cells thereon, where the structurally defined surface defines an ordered and regular array of openings through a thickness of the cell culture substrate. At least a portion of the cell culture substrate includes a sample substrate, the sample substrate being defined by a separation boundary between the sample substrate and a remainder of the cell culture substrate, and the separation boundary allows separation of the sample substrate from the remainder of the cell culture substrate. A bioreactor (300) having ports for aseptic removal of the sample substrate is also provided.

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.

This disclosure describes a biochemical reactor with fixed feed conduit. The biochemical reactor may include a tank configured to house immobilized carriers and fluid. The biochemical reactor may include a circulation conduit at least partially disposed within the tank. The circulation conduit may include a circulation inlet opening and a circulation outlet opening. The biochemical reactor may include one or more vanes disposed proximate to the circulation outlet opening. The one or more vanes may be configured to cause the immobilized carrier and the fluid exiting the circulation outlet opening to enter into a helical pattern. The biochemical reactor may include a feed conduit having a feed outlet. The feed outlet may be disposed between a first end and the circulation inlet opening. The feed conduit outlet may be immovable with respect to the circulation inlet opening.

The present invention provides an immobilized reaction device and a method for carrying out reaction by utilizing the immobilization technology. The immobilized reaction device includes a columnar reactor with an inlet and an outlet. The reactor is provided with an interior cavity which is defined by a top portion and a bottom portion opposite to each other, and a side wall connecting the top portion and the bottom portion.

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.

A fixed bed bioreactor assembly for culturing cells is provided and methods for sampling cell culture substrates from such assemblies. The assembly includes a bioreactor vessel having an interior space for culturing cells and a sidewall at least partly defining the interior space; and a plurality of cell culture substrate layers in the interior space, each layer having a structurally defined surface for culturing cells thereon. The structurally defined surface defines an ordered and regular array of openings through a thickness of the layer. The assembly further includes a sleeve at least partially surrounding the plurality of cell culture substrate layers and having at least one sample access window. The sample access window includes an opening in the sleeve to allow one or more layers of the cell culture substrate to be removed from the sleeve through the opening.

Methods for using vibration to harvest cells grown in 3D culture are provided. The methods entail the application of force cells attached to a 3D matrix of sufficient amplitude, frequency, and duration to detach cells from the matrix and to flush the detached cells out of the matrix material. An apparatus for performing the methods of the invention as provided.

A compact, high-yield, bio-reactor for use as small, medium and large-scale production unit for hosting and culturing of stem cells or living cells or micro organism and producing by multiplication or expression one or more biologic compounds for medical and biological applications.

The present invention relates a method for creating organoids, each simulating a biological organ having an organ development state. A substrate is provided, which has a plurality of cavities, each cavity being designed, in its size and form, to receive the organ to be simulated having the organ development state to be achieved. The cavities each have the form of a recess. The recesses have a length and a width, the length being greater than the width. Microfilaments are provided, each having a length which is greater than the width of the recesses and less than the length of the recesses. The individual microfilaments are arranged in the cavities. Living culturable cells are also arranged in the cavities. Conditions provided in the cavities for the culture of the cells on the individual microfilaments. The invention relates to a cell culture and a device for producing an arrangement for creating organoids.

Methods for using vibration to harvest cells grown in 3D culture are provided. The methods entail the application of force to cells attached to a 3D matrix of sufficient amplitude, frequency, and duration to detach cells from the matrix and to flush the detached cells out of the matrix material. An apparatus for performing the methods of the invention as provided.