Described herein are bioreactor support structures configured to be used with containers having different designs, and methods for making and using such bioreactors. The support structures described herein may include two or more agitator motors and control systems or an adjustable-position agitator motor, a removable spacer and/or lid, multiple configurations for ports and probes, and multiple exhaust filter heating blankets. Also described herein are methods of manufacturing a multi-agitator motor or adjustable-position agitator motor bioreactor, as well as methods of modifying an existing support structure to be used with a container not originally designed to be used with the existing support structure, and methods for operating these bioreactors.

A system for receiving a disposable bag (44) has a receiving container (10) with a container interior for receiving the disposable bag (44) and a temperature-control hollow wall (20) that at least partially surrounds the container interior of the receiving container (10). A temperature-control unit controls the temperature of the container interior by will a temperature-control medium arranged in the temperature-control hollow wall (20) at a maximum pressure of about 1 bar.

Digester (1) having an agitating device (10) and an agitating device (10) and a method for manufacturing an agitating device (10), the agitating device (10) comprising multiple agitator blades (21-29) which agitator blades (11-13) comprise a plurality of blade sections (21-29) angled relative to one another. The blade sections (21-29) of the agitator blade (11-13) are angled relative to one another such that the agitator blade gradient (11-13) decreases with the distance (30) from a central rotational axis (19) increasing to configure the agitator blade in a flow-optimized three-dimensional shape.

An agitator comprising a rotatable impeller comprising blades, magnets, and a shaft, wherein the impeller is configured to be driven by a drive unit magnetically coupled to the impeller, and an impeller seat receiving the rotatable impeller, the impeller seat comprising an upwardly arranged cylindrical housing, a flange, and a base, the cylindrical housing comprising a central opening for the impeller shaft, and the base comprising a collar and pins arranged to engage with a locking and centering mechanism, as well as a mixer engagement unit including the agitator, a mixer system, a mixing vessel, and methods of using the agitator, mixer engagement unit, mixer system, and mixing vessel, are disclosed.

A mixing system for mixing a liquid includes a first impeller segment having a first mount and a first mixing blade secured to the first mount and a second impeller segment having a second mount and a first mixing blade secured to the second mount, the second impeller segment being separate and discrete from the first impeller segment. One or more drive members are secured to the first impeller segment and the second impeller segment for concurrently rotating the first impeller segment and the second impeller segment about a rotational axis. The first impeller segment and the second impeller segment are secured to the one or more drive members so that a plane extending normal to the axis of rotation intersects with the first mixing blade of the first impeller segment and the first mixing blade of the second impeller segment.

A bladeless mixer for mixing a liquid, includes a cylindrical or truncated cone-shaped receptacle having an axis A and a radius R, the radius R being the shortest distance between the axis A and a side wall of the receptacle, the liquid to be mixed being placed in the receptacle and having an exposed surface at a height H measured along axis A; a member for tilting the receptacle such that axis A forms a non-zero-degree angle of up to 30° relative to the vertical direction; a member for imparting a rotational movement to the receptacle along axis A at an angular speed of rotation Ω; wherein the aspect ratio H/R of the height H to the radius R and the angular speed of rotation Ω are selected such that an inherent mode of inertia of the liquid has an unstable resonance when the receptacle is tilted and rotates.

A method for operating an agitating device and a digester, wherein the digester is filled with a substrate and an agitating device is in the digester. These steps are performed: a) A target load curve is lodged in the control device; b) the control device prescribes a target rotation speed; c) the control device operates the agitating device at an actual speed corresponding to a target speed; d) the control device captures an actual agitating device torque measurement value at the actual speed of rotation; e) the control device derives from the actual measurement value an actual characteristic value of the agitating device applied torque; f) the control device compares the derived actual characteristic value against the target characteristic value of the substrate resulting from the target load curve at the prescribed target speed; and g) the control device controls the agitating device in dependence on the result of comparison.

A vessel configured to contain a liquid is provided. The vessel includes a collapsible bad, a reusable support structure, a sensor, and a controller. The collapsible bag is operative to contain the liquid. The reusable support structure is operative to support the collapsible bag. The sensor is operative to measure a parameter within the collapsible bag. The controller is in electronic communication with the sensor and operative to introduce an antifoaming agent into the collapsible bag based at least in part on a signal received from the sensor.

A vessel configured to contain a liquid is provided. The vessel includes a collapsible bad, a reusable support structure, a sensor, and a controller. The collapsible bag is operative to contain the liquid. The reusable support structure is operative to support the collapsible bag. The sensor is operative to measure a parameter within the collapsible bag. The controller is in electronic communication with the sensor and operative to introduce an antifoaming agent into the collapsible bag based at least in part on a signal received from the sensor.

The present invention provides a continuous upstream manufacturing process for the production of bispecific antibody products, which comprise at least two binding domains. The process comprises at least the steps of (i) providing in a perfusion bioreactor at least one mammalian cell culture, which is capable of expressing the bispecific antibody product, (ii) growing the mammalian cell culture at a first perfusion rate until a set point viable cell density is reached, and (iii) maintaining perfusion culture at a second perfusion rate, wherein the bispecific antibody product concentration in the bioreactor is kept below a threshold value. The bispecific antibody product is then subject to subsequent downstream processing. Moreover, the invention provides a bispecific antibody product produced by the continuous upstream manufacturing process.