Bioreactor Models and Modeling Approaches

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Industrial biotechnology is a large and fast-growing field involving the utilization of cell factories to produce added-value products, but has yet to reach the level of maturity and cost-effectiveness of petrochemical industries. To reach this goal, many technological and operational challenges around the design of optimal bioreactor systems need to be addressed. Mathematical modeling plays an indispensable role in tackling important challenges toward this goal, by significantly improving process understanding and predicting complex biological phenomena. A bioreactor system is known for its hierarchically-arranged subsystems spanning multiple tiers of spatio-temporal scales from genome to metabolic network to culture broth, all of which contribute to bioreactor performance. Consequently, a bioreactor model needs to be constructed with sufficient information that allows it to generate a computationally trackable description for the target subsystems according to the challenges it aims to tackle.

Herein, we review the hierarchy of bioreactor modeling approaches starting from available black-box models, i.e. dynamic bioreactor models based on phenomenological description of kinetics. Incorporating such kinetics with topological information of the underlying metabolic network further generates grey-box models. We also discuss the development of white-box models with explicit description of intracellular kinetics, though such models are currently not suitable for routine industrial application. At the top hierarchy level, we finally review the reactor modeling approaches for studying mixing patterns in large-scale bioreactors.

Original languageEnglish
Title of host publicationComprehensive Biotechnology
EditorsMichael Butler
PublisherElsevier BV
Edition3rd edition
ISBN (Electronic)9780444640475
ISBN (Print) 9780444640468
Publication statusPublished - 17 Jul 2019

Publication series

NameComprehensive Biotechnology


  • Black-box model
  • grey-box model
  • white-box model
  • bioreactor model
  • modeling approach
  • biotechnology
  • bioprocess
  • metabolic modeling
  • dynamic modeling
  • Computational fluid dynamics
  • scale up


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