Provided herein are tubular membrane filter elements, tangential flow filtration systems comprising such filter elements and methods of using such filter elements and filtration systems.

Acoustic perfusion devices for separating biological cells from other material in a fluid medium are disclosed. The devices include an inlet port, an outlet port, and a collection port that are connected to an acoustic chamber. An ultrasonic transducer creates an acoustic standing wave in the acoustic chamber that permits a continuous flow of fluid to be recovered through the collection port while keeping the biological cells within the acoustic chamber to be returned to the bioreactor from which the fluid medium is being drawn.

Bioreactor systems and controlled operation of bioreactor systems are disclosed herein. The bioreactor systems can include at least one bioreactor chamber, at least one reservoir, a plurality of sensors, and a fluid circuit. The operational methods disclosed herein are directed towards growing cells or tissue while measuring various parameters, and a controlled operation of the various parameters during the operation of the bioreactor systems. The controlled operation of the parameters includes, for example, cell concentration; a rate of flow; a volume; a pH; a temperature; a level of oxygen; a level of carbon dioxide; a level of bicarbonate ion; nutrient compound; and any combination thereof.

Methods of treating cells are disclosed. The methods include introducing a media comprising at least about 1×10.sup.6 cells/mL into a perfusion chamber having a volume of 50 mL or less, introducing a volume effective to treat the cells of at least one additive selected from cell culture media, a transducing agent, a pH control agent, and a cell activator into the perfusion chamber, and withdrawing cell waste and byproducts from the perfusion chamber, and harvesting the treated cells. The methods may include introducing the media comprising at least about 3×10.sup.6 cells/mL into the perfusion chamber. The methods may include measuring and/or controlling at least one parameter of the cells or the media selected from pH, optical density, dissolved oxygen concentration, temperature, and light scattering.

The method for producing a three-dimensional artificial tissue is a method in which a three-dimensional artificial tissue extending in a predetermined direction is produced. The method includes: preparing a device including a culture tank having a culturing space surrounded by sidewalls, and a flow channel-forming member that penetrates through the sidewalls that face each other and is suspended in the culturing space along a predetermined direction; culturing cells in the culturing space and thereby forming a three-dimensional artificial tissue through which the flow channel-forming member penetrates; and removing the flow channel-forming member from the three-dimensional artificial tissue and thereby forming a perfusion flow channel that penetrates through the three-dimensional artificial tissue.

A cell culture apparatus is provided with: a cell culture bag that is formed of a tubular membrane material that can accommodate cells and a culture medium therein and that has openings at both ends in the longitudinal direction, and that forms a flow passage for the culture medium from one opening toward the other opening in the longitudinal direction of the tubular membrane material; a solution supply portion that is connected to the one opening and that supplies a solution to the inside of the cell culture bag; and a solution discharge portion that is connected to the other opening and that discharges the solution from the inside of the cell culture bag.

Acoustic perfusion devices for separating biological cells from other material in a fluid mixture are disclosed. The devices include an inlet port, an outlet port, and a collection port that are connected to an acoustic chamber. An ultrasonic transducer creates an acoustic standing wave in the acoustic chamber that permits a continuous flow of fluid to be recovered through the collection port while keeping the biological cells within the acoustic chamber to be returned to the bioreactor from which the fluid mixture is being drawn.

A microfluidic device, method and kit for assaying and/or culturing cells are provided. The microfluidic device comprises a well block comprising a plurality of microwells; at least one cell culture layer selected from a first cell culture layer comprising a plurality of microchannels, each microchannel being aligned with one of the plurality of microwells and being in fluid communication with the aligned microwells; and a second cell culture layer comprising a plurality of cell culture chamber wells, each cell culture chamber well being aligned with one of the plurality of microwells and being in fluid communication with the aligned microwells, and a plurality of outlets, each of the plurality of outlets corresponding to one of the plurality of cell culture chamber wells; and a base block, wherein the at least one cell culture layer is sealably coupled between the well block and the base block, thereby allowing fluid communication between the plurality of microwells in the well block and the at least one cell culture layer.

We have modified a commercially-available adherent cell culture bioreactor, developing a new sampling manifold configuration and new way of taking samples to reduce contamination risk.

The invention provides a bioreactor and methods for tissue cultivation. A bioreactor module comprises a container, a holder adapted to hold a scaffold containing an inherent vascular network, an inlet connectable to a vessel of the inherent vascular network, an inflatable device disposed within the container, and a pair of electrodes attached to opposing walls of the container, wherein the holder is removably receivable in the container and the inflatable device has a conduit extending through a wall of the container. An alternative embodiment provides an in-vitro method for tissue cultivation, comprising seeding an interior and an exterior of a vessel of an inherent vascular network of a scaffold with a first and a second cell type, respectively, and perfusing through the inherent vascular network with culture medium to facilitate compartmentalized co-cultivation of the first and the second cell type in different niches of the tissue. A further embodiment provides an in-vitro method for tissue cultivation, comprising seeding a surface of a scaffold with a predetermined cell type, and perfusing the scaffold with culture medium from an opposite surface of the scaffold through the scaffold and towards the seeded surface to create a nutrient/oxygen gradient and cause migratory diffusion induced penetration of cells towards the opposite surface.