A chemostat comprises a chamber containing media with cells; an input tube for delivering nutrient-laden media that support cell growth and division within the chamber at an inflow rate; and an output tube for withdrawing a sample from the chamber at an outflow rate. The inflow and outflow rates are regulated such that the chemostat is operable in a sample accumulation phase in which the outflow rate is zero and the inflow rate increases in proportion to an instantaneous volume of media in the chamber so as to accumulate the sample without changes in a metabolic state within the chamber, or a sample withdrawal phase in which the outflow rate is regulated at a higher rate than the inflow rate to withdraw the accumulated sample from the chamber rapidly at one time and the inflow rate remains in proportion to the instantaneous volume to maintain chemostasis in the chamber.

The present invention relates to a method for synthesizing an RNA molecule of a given sequence, comprising the step of determining the fraction (1) for each of the four nucleotides G, A, C and U in said RNA molecule, and the step of synthesizing said RNA molecule by in vitro transcription in a sequence-optimized reaction mix, wherein said sequence-optimized reaction mix comprises the four ribonucleoside triphosphates GTP, ATP, CTP and UTP, wherein the fraction (2) of each of the four ribonucleoside triphosphates in the sequence-optimized reaction mix corresponds to the fraction (1) of the respective nucleotide in said RNA molecule, a buffer, a DNA template, and an RNA polymerase.

Further, the present invention relates to a bioreactor (1) for synthesizing RNA molecules of a given sequence, the bioreactor (1) having a reaction module (2) for carrying out in vitro RNA transcription reactions in a sequence-optimized reaction mix, a capture module (3) for temporarily capturing the transcribed RNA molecules, and a control module (4) for controlling the infeed of components of the sequence-optimized reaction mix into the reaction module (2), wherein the reaction module (2) comprises a filtration membrane (21) for separating nucleotides from the reaction mix, and the control of the infeed of components of the sequence-optimized reaction mix by the control module (4) is based on a measured concentration of separated nucleotides.

This invention describes a design for a multiwell plate that contains integrated pumps that are used to stir each well of the plate. The device employs microfluidic logic technology to drive each peristaltic pump. This enables the plates to run autonomously, requiring only a static vacuum supply for power. The devices are entirely constructed out of low-cost polymers, with no electronics, and yet contains simple digital logic circuits to control the pumps. A stack of these plates may be run continuously in a standard cell culture incubator, allowing high-throughput culture of organoids.

Described are systems, methods, and devices relating to normothermic extracorporeal support of an organ, tissue, or bioengineered graft comprising cross-circulation (XC) perfusion for prolonged periods (days to weeks) via an XC perfusion circuit in connection with an extracorporeal host (e.g., animal, patient, organ transplant recipient) are disclosed. The XC perfusion circuit comprises auto-regulation of blood flow based on the trans-organ blood pressure difference between arterial and venous pressure. Recipient support enabled 36 h of normothermic perfusion that maintained healthy lungs with no significant changes in physiologic parameters and allowed for the recovery of injured lungs. Extended support enabled multiscale therapeutic interventions in all extracorporeal lungs. Lungs exceeded transplantation criteria.

A recipient for cell cultivation having an inner compartment adapted for cell growth, in one embodiment, an outer tubular wall extends in a longitudinal direction and delimits an outer boundary of the inner compartment in a radial direction. First and second ends delimit the inner compartment at the first respectively the second outer end of the outer tubular wall. A fixed packing in the inner compartment comprises a packing, such as a fiber matrix. Additional embodiments and related methods are also disclosed.

A cell processing system includes a first processor connectable to a source container filled with a biological fluid, a second processor, and a controller coupled to the processors. The first processor includes a separator configured to separate the biological fluid into at least two streams of material, and a first container configured to receive one of the streams. The second processor includes a magnetic separator configured to select target cells, the target cells being associated with magnetic particles, a second, pass-through container associated with the magnetic separator, the second container connected at a first end to the first container, and a third container connected to a second end of the pass-through container. One of the processors includes at least one pump configured to transfer material between the separator and the first container, and between the first container and the second container.

This large-scale cell culture system is for performing large-scale culture of cells by performing, in a closed system, subculture and transfer of spheroids and a culture medium by use of a vessel having a syringe structure, wherein the vessel comprises a front flange and a back flange which have a same circular outer shape and which are provided integrally with both ends of an outer cylinder part of the vessel, and the vessel allows rotary culture, utilizing the front flange and the back flange in a state where a head of the vessel is closed by a detachable cap and a space, in the vessel, closed by a gasket of a plunger is filled with a cell liquid obtained by suspending cells in a culture medium.

Described are systems, methods, and devices relating to normothermic extracorporeal support of an organ, tissue, or bioengineered graft comprising cross-circulation (XC) perfusion for prolonged periods (days to weeks) via an XC perfusion circuit in connection with an extracorporeal host (e.g., animal, patient, organ transplant recipient) are disclosed. The XC perfusion circuit comprises auto-regulation of blood flow based on the trans-organ blood pressure difference between arterial and venous pressure. Recipient support enabled 36 h of normothermic perfusion that maintained healthy lungs with no significant changes in physiologic parameters and allowed for the recovery of injured lungs. Extended support enabled multiscale therapeutic interventions in all extracorporeal lungs. Lungs exceeded transplantation criteria.

A microfluidic chip is configured to determine DILI parameters. The microfluidic chip includes a cell chamber hosting a tissue culture comprising liver tissue; a reoxygenation chamber configured to add oxygen to a fluid media; a fluid loop configured to recirculate the fluid media through the cell chamber and the reoxygenation chamber and supply oxygenated fluid media to the tissue culture; and an oxygen sensor configured to measure an oxygen concentration within the fluid media. The microfluidic chip includes a controller configured to perform operations including recirculating the fluid media in the fluid loop, the fluid media comprising a drug dose; obtaining measurements of the oxygen concentration at a sequence of time points during recirculating; and determining, based on the measured oxygen concentration, at least one physiologic parameter value of the tissue culture that describes a clinical test metric describing a damage level to the tissue culture.

The present invention provides a membrane bioreactor for deep-sea cold seeps. The bioreactor is used for simulating a biomembrane growth process during anaerobic oxidation of methane (AOM) in the cold seeps and monitoring changes of environmental conditions thereof. The present invention further provides an online environmental parameter measurement system for a membrane biological reaction in the deep-sea cold seeps. The system includes a fluid supply unit used for generating saturated methane fluid and injecting the saturated methane fluid into the membrane bioreactor for the deep-sea cold seeps at a microflow, and a pressurization system used for ensuring stability and consistency of internal environmental pressure of the system in a simulation process.