An integrated microfluidic chip and a single-cell culture, screening, and export method applying the same are disclosed; the chip includes a base, an inlet flow channel, an outlet flow channel, a plurality of common flow channels and a plurality of functional units, wherein two ends of the common flow channel are connected to the inlet flow channel and the outlet flow channel, respectively, wherein each of the functional units includes a single-cell introduction port, a cell culturing-screening chamber, a cell export chamber, a cell export port, and a drive element, wherein the drive element is used to provide power to liquid to introduce single cells entering the common flow channels into the cell culturing-screening chamber, and after culturing and screening, to export target cell population in the cell culturing-screening chamber through the cell export port.

The bioprocessing perfusion system (10) includes a bioreactor (12) and a feed flow path (14). A first tangential flow filter (16) is coupled to the bioreactor (12) via the feed flow path (14) and a second tangential flow filter (18) is coupled to the bioreactor (12) via the feed flow path (14). The first tangential flow filter (16) is a microfiltration-type filter and the second tangential flow filter (18) is an ultrafiltration-type filter. The first tangential flow filter (16) and the second tangential flow filter (18) are further coupled to a receiving unit (58) via the permeate flow path (60). The first tangential flow filter (16) and the second tangential flow filter (18) are further coupled to the bioreactor (12) via the retentate flow path (46). A control unit (82) is communicatively coupled to the first feed control device (42), the second feed control device (44), the feed drive unit (40), the first permeate control device (64), the second permeate control device (66), the first retentate control device (48), and the second retentate control device (50).

The present invention provides a culture method capable of maturing an organoid through long-term culture, and suitable for producing a conformational organ. The culture method of the present invention is a method for culturing an organoid and/or cells constituting an organ immobilized in a chamber with a culture fluid perfused, and the culture fluid is perfused in such a manner as to generate a turbulent flow in the chamber.

A cell culture matrix is provided that has a substrate with a first side, a second side opposite the first side, a thickness separating the first side and the second side, and a plurality of openings formed in the substrate and passing through the thickness of the substrate. The plurality of openings allow flow of at least one of cell culture media, cells, or cell products through the thickness of the substrate, and provides a uniform, efficient, and scalable matrix for cell seeding, proliferation, and culturing. The substrate can be formed from a woven polymer mesh material that provides a high surface area to volume ratio for cells and good fluid flow through the matrix. Bioreactor systems incorporating the cell culture matrix and related methods are also provided.

A method for achieving microfluidic perfusion of a spheroid, the method being implemented in a microfluidic device that includes a cavity for hydrodynamically trapping the spheroid, the method including performing a first injection of a gel containing the spheroid into the microfluidic network, hydrodynamically trapping the spheroid in the trapping cavity of the microfluidic network, performing a second injection of a fluid that is non-miscible with the gel into the microfluidic network with a view to flushing away gel present in the network, except in the trapping cavity, cross-linking the gel present around the spheroid, in the trapping cavity, performing a third injection of a culture medium into the microfluidic network with a view to perfusing the spheroid petrified in its gelled environment, and located in the trapping cavity.

The present invention relates to cell culture media comprising N-lactoyl derivatives of one or more amino acid. The poor solubility of some amino acids in cell culture media is overcome by substituting them with an N-lactoyl derivative.

The present invention relates to a novel bioreactor system for preparing an engineered three- dimensional biological tissue construct. The bioreactor system comprises a cultivation chamber that is designed to allow the formation, cultivation and the subsequent testing and/or stimulation of tissue constructs on one or more support elements with a minimum risk of microbial contamination or mechanical damage The invention furthermore relates to a method for preparing an engineered tissue construct using the novel bioreactor system. The invention also relates to the use of the bioreactor system for preparing engineered biological tissue constructs, preferably tissue constructs which are suitable for being used in clinical tissue replacement and reconstructive therapy, drug development, drug screening, toxicity testing, cosmetic studies, safety testing, developmental studies, disease modeling, or food purposes.

A cell culture system is provided that includes a cell culture vessel having an interior cavity to house a cell culture substrate in a cell culture space, and at least one port for at least one of fluid inlet to the interior cavity and fluid outlet from the interior cavity. The system further includes a piston having a distal end disposed in the cell culture vessel above the cell culture space, the distal end of the piston being sealed with an airtight seal within the interior cavity. The system also includes a driver coupled to the piston to move the piston so as to increase and decrease a distance between the distal end and the cell culture space. The driver can pressurize the interior cavity via actuation of the piston to harvest cells from the cell culture space through the at least one port.

A perfusion manifold assembly is described that allows for perfusion of a microfluidic device, such as an organ on a chip microfluidic device comprising cells that mimic cells in an organ in the body, that is detachably linked with said assembly so that fluid enters ports of the microfluidic device from a fluid reservoir, optionally without tubing, at a controllable flow rate.

A culture module is contemplated that allows the perfusion and optionally mechanical actuation of one or more microfluidic devices, such as organ-on-a-chip microfluidic devices comprising cells that mimic at least one function of an organ in the body.

A process and system for producing an inoculum for downstream cell production is disclosed. The inoculum is produced in a perfusion bioreactor in which the nutrient media feed is increased as the biomass concentration increases within the bioreactor. A biomass sensor can be used to periodically or continuously monitor biomass concentration. This information can be fed to a controller for automatically increasing nutrient media feed rates in a manner that is directly proportional to producing an inoculum with an increase cell density. The process and system can also include an automated subsystem for maintaining constant volume levels within the perfusion bioreactor during the process.