Applying mechanistic models in bioprocess development.

Rita Lencastre Fernandes, Vijaya Krishna Bodla, Magnus Carlquist, Anna-Lena Heins, Anna Eliasson Lantz, Gürkan Sin, Krist V Gernaey

Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

1 Downloads (Pure)

Abstract

The available knowledge on the mechanisms of a bioprocess system is central to process analytical technology. In this respect, mechanistic modeling has gained renewed attention, since a mechanistic model can provide an excellent summary of available process knowledge. Such a model therefore incorporates process-relevant input (critical process variables)-output (product concentration and product quality attributes) relations. The model therefore has great value in planning experiments, or in determining which critical process variables need to be monitored and controlled tightly. Mechanistic models should be combined with proper model analysis tools, such as uncertainty and sensitivity analysis. When assuming distributed inputs, the resulting uncertainty in the model outputs can be decomposed using sensitivity analysis to determine which input parameters are responsible for the major part of the output uncertainty. Such information can be used as guidance for experimental work; i.e., only parameters with a significant influence on model outputs need to be determined experimentally. The use of mechanistic models and model analysis tools is demonstrated in this chapter. As a practical case study, experimental data from Saccharomyces cerevisiae fermentations are used. The data are described with the well-known model of Sonnleitner and Käppeli (Biotechnol Bioeng 28:927-937, 1986) and the model is analyzed further. The methods used are generic, and can be transferred easily to other, more complex case studies as well.
Original languageEnglish
Title of host publicationAdvances in Biochemical Engineering/Biotechnology
PublisherSpringer
Publication date2013
Pages137–166
ISBN (Print)978-3-642-36837-0
ISBN (Electronic)978-3-642-36838-7
DOIs
Publication statusPublished - 2013
SeriesAdvances in Biochemical Engineering/Biotechnology
Volume132
ISSN0724-6145

Keywords

  • Fermentation
  • Identifiability
  • Modeling
  • Monte Carlo
  • PAT
  • Saccharomyces cerevisiae
  • Sensitivity
  • Uncertainty

Cite this

Lencastre Fernandes, R., Bodla, V. K., Carlquist, M., Heins, A-L., Eliasson Lantz, A., Sin, G., & Gernaey, K. V. (2013). Applying mechanistic models in bioprocess development. In Advances in Biochemical Engineering/Biotechnology (pp. 137–166). Springer. Advances in Biochemical Engineering/Biotechnology, Vol.. 132 https://doi.org/10.1007/10_2012_166