The requirements of a bioreactor/fermenter for microbial fermentations are fundamentally different to those for mammalian cell cultivations. Microbial processes require higher gas flow rates, tip speeds and greater cooling capacities to support the higher growth rates and greater oxygen demands of microbial cultures.
Moreover, highly dynamic microbial processes cause rapid changes in process parameters and place great demands on the performance of the bioreactor controller. The precise control of critical process parameters is needed to achieve optimal product quality and prevent the formation of unwanted byproducts.
This application note describes a highly demanding Escherichia coli fed-batch cultivation and evaluates the performance of the new BIOSTAT B-DCU in such a process. It focuses on describing the control accuracy of the main process control parameters for pO2, pH and temperature.
Maintaining a constant pO2 during the course of a microbial cultivation is a challenging task for a bioreactor system and requires the precise control of a large range of gas flow rates. In addition, a microbial bioreactor system for process development and characterisation should be capable of being used with a range of different cultivation volumes. The BIOSTAT B-DCU meets these requirements and features digital mass flow controllers with a gas flow range of 1:200 (0.05–10 L/min) in combination with the possibility to combine additional mass flow controllers to further extend the flow rate ranges. This enables different cultivation volumes with the same bioreactor controller.
High growth rate cultivation reactions with E. coli generate a large amount of biological heat. To remove this requires an adequate cooling system that provides effective heat transfer and temperature control close to a set point.
To deliver the optimum product quality, scientists must have a thorough understanding of the manufacturing processes. The BIOSTAT B-DCU features advanced sensors and analytics that form the basis for comprehensive process understanding. Off-gas analysis supports the characterisation of cell metabolism during processing. During these experiments, the BIOSTAT B-DCU was equipped with the BioPAT Xgas off-gas analyser. In addition, online glucose, ethanol and methanol determination — as well as inline turbidity and capacitance sensors — provide even greater process understanding when used in conjunction with the BIOSTAT B-DCU.
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