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Methodologies for Scale-down of Microbial Bioprocesses

Maria Papagianni

Much research has been done on bioreactor hydrodynamics and their interactions with various microbial cell mechanisms and several methodologies have been proposed in order to resolve scale-up problems. Among them is the approach of scale-down and regime analysis. Regime analysis at production scale has to define the rate-limiting mechanisms of the process and identify the ruling regime. Such an analysis, based on characteristic times, can give valuable information for scale translation and optimization of bioprocesses. An efficient scale-down bioreactor has to create conditions that will be representative for the conditions occurring at large scale. Miniaturised bioreactor (MBR) systems may serve as scale-down tools especially in early-stage process operations. In later stages, e.g. optimization of process conditions and operations, only scaleable apparatus can be applied successfully. The choice of the scale-down method, and therefore the kind of the applied scale-down bioreactor, should be based on the characteristics of the process. The constructed models and the rules used to scale-down the process will be used in scaling-up the optimized conditions at production scale. The paper reviews the systematic approach of scale-down methodologies.