A conjugation device includes at least one flow reactor having an inlet and an outlet, the flow reactor(s) being completely filled with a support such as a matrix including 1) chromatography beads, fibers or membranes, and 2) a biologic catalyzer, namely the enzyme ligase, which is immobilized onto this support; a fluid delivery unit in fluid communication with the inlet of the flow reactor(s) and configured to continuously provide the flow reactor(s) with at least one kind of reaction fluid such as antibody and linker-payload according to stages of the conjugation process, the at least one kind of process fluid including a first moiety and a second moiety of a conjugate to be produced; and a fluid collection unit in fluid communication with the outlet of the flow reactor(s) and configured to control collection of fluid flowing out of the outlet of the flow reactor(s) according to the stages of the conjugation process. In a period of enabling the at least one kind of reaction fluid to continuously flow through the flow reactor(s), a conjugation reaction is conducted between the first moiety and the second moiety under catalysis of the ligase to produce the conjugate.

The present invention provides for a fully integrated microfluidic system capable of producing single-dose amounts of biotherapeutics at the point-of-care wherein protein production, purification and product harvest are all integrated as a single microfluidic device which is portable and capable of continuous-flow production of biotherapeutics at the microscale using a cell-free reaction system.

A device for homogenizing a multicomponent fluid including a main channel, a first and a second buffer channels, a collector connected to the main channel with a main conduct, to the first buffer channel with a first fiber and to the second buffer channel with a second fiber. The collector further includes a flow separation point aimed at dividing the main conduct into the first and second fibers, a pumping unit configured to move the multicomponent fluid from the main channel to the first or the second buffer channels through the collector and move the multicomponent fluid from the first or the second buffer channels to the main channel through the collector.

The invention relates to a modular processing system for biopharmaceutical and/or chemical processes, comprising: at least one processing unit; at least one adapter plate, which can be directly or indirectly fluidically connected to the processing unit, wherein the adapter plate has at least one adapter channel, through which at least one fluid flow can flow to the processing unit, wherein the adapter plate also has at least one deflection element and/or a pump and/or at least one valve; and an external control device. The adapter plate is designed in such a way that the fluid flow to the processing unit can be at least partially deflected with the at least one deflection element in the adapter channel and/or the fluid flow, preferably its pressure, is controllable with the at least one valve and/or the pump in the adapter channel. A respective at least one sensor is embedded in the processing unit and/or in the adapter plate, in order to detect at least one property of the fluid flow in the processing unit or the adapter plate. The external control device can be coupled to the at least one sensor in such a way that measurement data of at least one sensor can be read out, and the fluid flow in the processing unit and or the adapter plate can be centrally controlled based on the read-out measurement data. The invention also relates to a method for centrally controlling a modular processing system for biopharmaceutical and/or chemical processes.

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.

Disclosed herein are compositions, devices, methods, processes, and systems for culturing of large quantities of mammalian cells in suspension culture. Also disclosed are unique and surprising cell populations derived from the disclosed methods, processes, and systems. In many embodiments, the cells are cultured in suspension in liquid culture media that is agitated to maintain the cells in suspension, and agitation increases to maintain cells in suspension while growing and dividing to create cell spheres. The disclosed devices, methods, processes, and systems are useful in tailoring characteristics of the resulting cells based on characteristics of donor subject/initial cells. The disclosed cell populations are useful in treating subjects with cell based therapies in need thereof for various diseases and conditions.

An apparatus for culturing cells includes a bioreactor. The bioreactor may be modular and may include in a chamber a fixed bed, such as an unstructured or structured fixed bed (such as a spiral bed) for culturing cells, with a return column arranged centrally within the chamber. The modular bioreactor may include a plurality of structured fixed bed arranged in a stacked configuration. The modular bioreactor may include an outer casing forming a space for conditioning (e.g., insulating, heating, cooling) at least a chamber in which cells are cultured. The bioreactor may also include an impeller with radially curved blades, and may also suspend the impeller so that it may move from side-to-side and align with an external drive. Related methods are also disclosed.

A process is provided for isolating and analyzing microorganisms contained in a sample by collecting a determined volume in a sample, the determined volume representing all or part of this sample, likely to contain at least one microorganism. The collected volume is then split up into a plurality of compartments having a culture medium, the volume of each compartment being smaller than 10 μL, each compartment being isolated from the other compartments and having no interface with the ambient atmosphere. At least one microorganism is incubated in the compartments for determined durations, and compartments are detected that contain at least one microorganism. The incubation may be extended after detecting compartments so that at least one microorganism having a defined quantity can be detected, and then the content of the detected compartments can be recovered. Finally, at least one functional parameter relative to a microorganism in the compartments is determined.

The present invention relates to methods and systems for performing perfusion cell culture whereby the supernatant of the bleed stream is recovered.

A device for treatment of cells with particles is disclosed. The device includes a semi-permeable membrane positioned between two plates, the first plate defining a first flow chamber and comprising a port, a flow channel, a transverse port, and a transverse flow channel, the first flow chamber constructed and arranged to deliver fluid in a transverse direction along the first side of the semi-permeable membrane, the second plate defining a second flow chamber and comprising a port. A method for transducing cells is disclosed. The method includes introducing a fluid with cells and viral particles into a flow chamber adjacent a semi-permeable membrane such that the cells and the viral particles are substantially evenly distributed on the semi-permeable membrane. The method also includes introducing a recovery fluid to suspend the cells and the viral particles, and separating the cells from the viral particles. A method of activating cells is disclosed.