Bioprocess scale-up/down as integrative enabling technology
from fluid mechanics to systems biology and beyond
Frank Delvigne (Sart Tilman B52)
Ralf Takors (University of Stuttgart)
Rob Mudde (TU Delft - ImPhys/Imaging Physics, TU Delft - ChemE/Transport Phenomena)
Walter van Gulik (TU Delft - OLD BT/Cell Systems Engineering)
Henk Noorman (DSM, TU Delft - BT/Bioprocess Engineering)
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Abstract
Efficient optimization of microbial processes is a critical issue for achieving a number of sustainable development goals, considering the impact of microbial biotechnology in agrofood, environment, biopharmaceutical and chemical industries. Many of these applications require scale-up after proof of concept. However, the behaviour of microbial systems remains unpredictable (at least partially) when shifting from laboratory-scale to industrial conditions. The need for robust microbial systems is thus highly needed in this context, as well as a better understanding of the interactions between fluid mechanics and cell physiology. For that purpose, a full scale-up/down computational framework is already available. This framework links computational fluid dynamics (CFD), metabolic flux analysis and agent-based modelling (ABM) for a better understanding of the cell lifelines in a heterogeneous environment. Ultimately, this framework can be used for the design of scale-down simulators and/or metabolically engineered cells able to cope with environmental fluctuations typically found in large-scale bioreactors. However, this framework still needs some refinements, such as a better integration of gas–liquid flows in CFD, and taking into account intrinsic biological noise in ABM.
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