Embodiments described herein generally provide for the expansion of cells in a cell expansion system using an active promotion of a coating agent(s) to a cell growth surface in some embodiments. A coating agent may be applied to a surface, such as the cell growth surface of a hollow fiber in a bioreactor, by controlling the movement of a fluid in which a coating agent is suspended, by changing flow rates, by changing flow directions, by rotation of the bioreactor, and/or combinations thereof.

A bioprocessing system (100, 200) including a storage unit (102, 202) for storing a feed fluid (103, 203), a filter (106, 206) coupled to the storage unit (102, 202) via a feed path (104, 204), and a feed pump (114, 212) coupled to the feed path (104, 204). The bioprocessing system (100, 200) further includes a collection unit (102, 216) coupled to the filter (106, 206) via a downstream path (118, 218) and a turbidity sensor (134, 224) coupled to the downstream path (118, 218). Furthermore, the bioprocessing system (100, 200) includes a processing unit (136, 226) configured to receive an output from the turbidity sensor (134, 224) and determine a concentration of a product in a filtration fluid (121, 222) based on the output. The processing unit (136, 226) is further configured to monitor an operating condition of the filter (106, 206) on-line based on concentration of the product.

Multiplanar microfluidic devices are provided that facilitate direct transverse fluid communication between a first microfluidic channel a plurality of adjacent microfluidic channels, where the adjacent microfluidic channels reside both laterally adjacent and vertically adjacent to the first microfluidic channel, thereby facilitating transverse diffusion to or from the adjacent microfluidic channels in both lateral and vertical directions. Geometrical meniscus-pinning features, such as meniscus-pinning ridge structures, are provided between adjacent microfluidic channels to restrict transverse flow between the microfluidic channels. Accordingly, a gel structure may be formed within the first microfluidic channel and one or more of the adjacent microfluidic channels can function as a perfusion channel, for example, for delivering media to cells residing withing the gel structure. Such devices may be extended and/or arrayed to include multiple channels with laterally and vertically adjacent perfusion microfluidic channels, optionally with shared lateral perfusion microfluidic channels among adjacent pairs of devices.

This disclosure relates to the use of a hydrophobic hollow fiber filter for the filtration of cell cultures and other biological perfusions, due to its resistance to fouling, as well as the ability to filter solutions with a high solid content. A hydrophobic hollow fiber filter may be used within a filter housing in conjunction with a process vessel and a traditional separation system. When the system is used with alternating tangential flow or tangential flow filtration, the hydrophobic hollow fiber filter results in more effective filtration of the filtrate, leading to greater concentration of the retentate, even in solution containing high levels of solids.

Disclosed herein is a bioreactor system that allows active perfusive flow through a porous support medium enabling 3D growth of biological samples. In some embodiments, the system comprises a sample well filled with a three-dimensional (3D) cell growth medium. The system can further comprise a liquid medium reservoir fluidly connected to the sample well by a first filter material. The system can further comprises a medium collection chamber fluidly connected to the sample well by a second filter material. In some embodiments, application of negative gage pressure to the medium collection chamber or positive pressure to the liquid medium reservoir draws fluid from the liquid medium reservoir, through the first filter material, into the sample well where it permeates the three-dimensional cell growth medium, through the second filter material, and finally into the medium collection chamber.

System and method includes a body having a central microchannel separated by one or more porous membranes. The membranes are configured to divide the central microchannel into a two or more parallel central microchannels, wherein one or more first fluids are applied through the first central microchannel and one or more second fluids are applied through the second or more central microchannels. The surfaces of each porous membrane can be coated with cell adhesive molecules to support the attachment of cells and promote their organization into tissues on the upper and lower surface of the membrane. The pores may be large enough to only permit exchange of gases and small chemicals, or to permit migration and transchannel passage of large proteins and whole living cells. Fluid pressure, flow and channel geometry also may be varied to apply a desired mechanical force to one or both tissue layers.

Embodiments described herein generally provide for the expansion of cells in a cell expansion system using an active promotion of a coating agent(s) to a cell growth surface in some embodiments. A coating agent may be applied to a surface, such as the cell growth surface of a hollow fiber in a bioreactor, by controlling the movement of a fluid in which a coating agent is suspended, by changing flow rates, by changing flow directions, by rotation of the bioreactor, and/or combinations thereof.

A method for displacing a fluid and simultaneously gas enriching a liquid cell culture medium with a gas. The method includes injecting a controlled volume of a gas or gas mixture into a one chamber by using a gas flow controller, the injection taking place through a gas inlet into a volume of liquid. This injection produces bubbling and agitation of the volume of liquid; a build-up of gas or gas mixture due to buoyancy in a hermetic space formed by the volume of liquid and the chamber, and a pressure increase in the chamber until a sufficient controlled pressure is reached of less than or equal to 10 bar. This increase displaces the volume of liquid by a fluid outlet connecting the volume of liquid to the exterior of the chamber. Also provided are a device implementing the method and a cell culture system in a multi-well culture plate.

The invention relates to the field of microcarrier perfusion culture of adherent cells. Specifically, the present invention relates to a high-density microcarrier retention device for perfusion culture of adherent cells, a microcarrier perfusion culture system for adherent cells containing the device, and methods of use thereof. The retention device of the present invention includes a sedimentation chamber, a pipeline connected to a bioreactor, a microcarrier retention filter membrane, a liquid backflushing device, an air backflushing device, a peristaltic pump and a pipeline connected to a receiver. The device has high efficiency in promoting the separation of microcarriers from cell culture medium and is helpful for perfusion culture of adherent cells and microcarriers. The retention device makes the culture volume in the bioreactor more flexible, can perform perfusion culture of 20%-100% of the maximum culture volume of the bioreactor, and the retention device can be linearly amplified according to the amplification of the bioreactor volume.

Described herein is a cell culture system for constructing a perfusable network of self-assembled cells comprising a multi-well plate embedded with microchannels connecting a central well with at least one inlet well and at least one outlet well, the central well for culturing seeded cells within an extracellular matrix, wherein the perfusable network allows perfusion through the microchannels connecting the central well with at least one inlet well and at least one outlet well. The cell culture system allows the array of perfusable networks formed, connected, and perfused inside the multi-well plate to be accessible and/or extractable from the top of the central well. In aspect, the cell culture system can improve the experimental throughputs of organ-on-a-chip systems and expand the application of microphysiological systems to regenerative cell therapy. A perfusable network of self-assembled cells and method of making thereof using the cell culture system described herein are also provided.