The present disclosure relates to multistep chromatographic methods for preparing extracellular vesicles (EVs). The methods were demonstrated to be effective in preparing highquality EVs in a large scale. The methods enable preparation of EVs for therapeutic and diagnostic applications, and isolation and/or sub-fractionation of EVs with desired properties for specific use.

There is provided a process for the separation of molecules from a suspension comprising cells at a concentration of at least 56×10.sup.6 cells/ml, comprising the steps of: a) providing magnetic particles having a specific interaction with said molecules to be separated, b) mixing the magnetic particles with the cell suspension containing the molecules, c) bringing the cell suspension in contact with a magnetic field provided by a magnetic separation device to collect the magnetic particles, d) decreasing or removing said magnetic field and collecting said magnetic particles carrying said molecules, and e) removing said molecules from said magnetic particles, to provide a concentrated fraction of said molecules, and/or provide partial or complete removal of impurities and cells from the fraction containing the molecules. Advantages include that the yield increases, the volume of the bioreactor and other equipment can be made smaller so that the process becomes more economical.

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

Systems (100) and methods for perfusion control in a bioreactor (120) are provided. The system (100) comprises a media container (110) connected to the bioreactor (120) and weighing scales (113, 123) measure weight of the bioreactor (120) and the media container (110). A plurality of controllers (225, 245) are connected to the weighing scales and configured to continuously feed the media from media container (110) to the bioreactor (120) at a user defined rate using a motor pump (112). A filter (130) is provided to receive feed from the bioreactor (120) through a recirculation line (121) and a permeate flow line (141) is connected to the filter (130) to flow out the permeate from the filter (130). When weight of the bioreactor (120) goes beyond the upper (U) or lower (L) permissible weight limit, a controller (225) connected to the weighing scale of the bioreactor (120) sends a signal to operate the permeate motor pump (142) either to flow out the permeate from the filter (130) or to stop the motor pump (142).

A bioreactor for producing hydrogen gas and other metabolites. The bioreactor utilizes light, fermentation, and other metabolic processes for the production of metabolites, derived from various microorganisms contained within the bioreactor through respective metabolic pathways. The bioreactor comprises a main reactor chamber, a semipermeable membrane, a sleeve, a power supply, a substrate medium, a heating member, a plurality of tubing members, a collection reservoir, a pressure-sealed connecter member, and an agitator.

A device for simulating a function of a tissue includes a first structure, a second structure, and a membrane. The first structure defines a first chamber. The first chamber includes a matrix disposed therein and an opened region. The second structure defines a second chamber. The membrane is located at an interface region between the first chamber and the second chamber. The membrane includes a first side facing toward the first chamber and a second side facing toward the second chamber. The membrane separates the first chamber from the second chamber.

Aspects of the present disclosure relate to systems and methods for manufacturing biologically-produced pharmaceutical products. Some of the systems described herein comprise an upstream component comprising a bioreactor and at least one filter (e.g., a filter probe) integrated with a downstream component comprising a purification module comprising at least a first partitioning unit and a second partitioning unit. In some embodiments; these integrated biomanufacturing systems may be operated under continuous or conditions and may be capable of efficiently producing pure, high-quality pharmaceutical products.

Provided are a method and a system for culturing cells and harvesting biologics. More particularly process for cell culture by intensified perfusion with continuous harvest and without cell bleeding is provided.

The invention relates to a substrate for testing samples, in particular cells or molecules, wherein the substrate comprises a fluid system comprising a sample chamber configured in the substrate for storing and testing samples and at least one liquid reservoir in fluid communication with the sample chamber, and wherein the substrate comprises a passive blocking element capable of assuming a closed position and an open position, wherein in the closed position a fluid exchange between the sample chamber and the liquid reservoir is blocked.

A Disposable Bioprocess System having a Single-Use-Bioreactor, a Single-Use-Pump and a single-use micro-organism retention filter. Combined most suitable for cultivation of suspended micro-organisms in a liquid media at high micro-organism concentration in a perfusion mode continuous process for expression of biological material. The inlet port of the liquid Single-Use-Pump connects via a valve to the broth reservoir of the Single-Use-Bioreactor through a liquid conveying port. The outlet port of the liquid pumping Single-Use-Pump connects via a valve to a micro-organism retention filter. And a method for operating the sterile Disposable Bioprocess System in perfusion mode for continuously processing.