Bioprocess scale-up/down as integrative enabling technology: from fluid mechanics to systems biology and beyond

Microb Biotechnol. 2017 Sep;10(5):1267-1274. doi: 10.1111/1751-7915.12803. Epub 2017 Aug 14.


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.

MeSH terms

  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bioreactors / microbiology
  • Fungi / genetics
  • Fungi / metabolism*
  • Industrial Microbiology*
  • Metabolic Engineering
  • Systems Biology