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).

An inverted conical bioreactor is provided for growing cells or microorganisms. The bioreactor has an internal space and a perforated barrier within the vessel, through which a liquid may flow, where cells or microorganisms cannot pass through the perforated barrier. The perforated barrier divides the internal space of the bioreactor into a first chamber and a second chamber. Cells are grown within the second chamber and can be perfused by re-circulating the liquid, for example a growth medium, through the bioreactor. Various inlet ports and outlet ports allow controlling the parameters of flow of the growth medium.

A system and method for the production of microbial consortiums and by-product material is provided. A physical containment system comprising phase spaces arranged in a discrete order to favor specific biological reactions is also provided. Phase profiles and phase data sets include the pre-determined physical and biological parameters for the phase space transitions. Movement of material from one phase to the next is hydraulically balanced enabling working fluid to continuously move in a fixed direction and rate of flow. Continuous monitoring of phase profiles and phase data sets provide feedback to the system enabling alteration of the conditions in the system to control reactions therein.

This invention concerns an integrated microfluidic system that utilizes microfluidic chip technology to receive a patient sample including cells, expand the cells, reprogram the expanded cells and then store the reprogrammed cells in a microfluidic chip. These microfluidic chips with stored reprogrammed cells may then be used in scenarios of genetic differentiation into specific cell types. Overall this system and workflow is suitable as a hospital based device that will allow the generation of iPSCs from every patient for downstream diagnostic or therapeutic use.

Techniques for predicting an amount of at least one biomaterial produced or consumed by a biological system in a bioreactor are provided. Process conditions and metabolite concentrations are measured for the biological system as a function of time. Metabolic rates for the biological system, including specific consumption rates of metabolites and specific production rates of metabolites are determined. The process conditions and the metabolic rates are provided to a hybrid system model configured to predict production of the biomaterial. The hybrid system model includes a kinetic growth model configured to estimate cell growth as a function of time and a metabolic condition model based on metabolite specific consumption or secretion rates and select process conditions, wherein the metabolic condition model is configured to classify the biological system into a metabolic state. An amount of the biomaterial based on the hybrid system model is predicted.

A method for optimizing a process (PROC) to produce a biochemical product (P) defined by a quality attribute, the process being controlled by an actuation parameter (C) and being monitored to get a measured value (T). The method includes training a predictive model (PRED) on a training database; and deploying the trained predictive model (PRED) to provide a correction actuation parameter (dC) when a predicted quality attribute (pQA) is out of a targeted quality attribute interval (QAmin, QAmax). The method also includes a step of designing a physical model of the process (PROC) able to provide a simulated quality attribute, the training database comprising simulated quality attributes computed from the physical model and experimental quality attributes computed from biochemical products (P) previously produced.

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.

The present subject matter discloses a bioreactor apparatus. The bioreactor apparatus comprises a bioreactor vessel configured to culture cells. The bioreactor apparatus furthermore comprises a sensor configured to measure Dissolved Oxygen (DO) in the bioreactor vessel. The DO measurements comprise a plurality of DO values recorded at, at least, a plurality of time instances during operation of the bioreactor apparatus. The bioreactor apparatus furthermore comprises a controller configured to obtain the DO measurements. The controller furthermore is to determine, in real-time or approximately real-time, an oxygen mass transfer co-efficient (kLa) associated with the operation of the bioreactor apparatus. Furthermore, the controller is configured to control, in real-time or approximately real-time, at least one cell culture parameter associated with the operation of the bioreactor apparatus based on the kLa.

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.

A calibration apparatus comprises estimation circuitry configured to estimate, based on a calibration factor, an estimated number of cells of a first type in a dyed biological sample containing an unknown number of cells. Determination circuitry determines the actual number of cells of the first type in the dyed biological sample. Processing circuitry adjusts the calibration factor. The estimation circuitry is configured with the processing circuitry to estimate the estimated number of the cells of the first type in the dyed biological sample one or more times, based on a different value of the calibration factor for each of the one or more times, until the estimated number of the cells of the first type approaches the actual number of cells of the first type.