Toward intensifying design of experiments in upstream bioprocess development: An industrial Escherichia coli feasibility study

Moritz von Stosch, Jan Martijn Hamelink, Rui Oliveira

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

In this study, step variations in temperature, pH, and carbon substrate feeding rate were performed within five high cell density Escherichia coli fermentations to assess whether intraexperiment step changes, can principally be used to exploit the process operation space in a design of experiment manner. A dynamic process modeling approach was adopted to determine parameter interactions. A bioreactor model was integrated with an artificial neural network that describes biomass and product formation rates as function of varied fed-batch fermentation conditions for heterologous protein production. A model reliability measure was introduced to assess in which process region the model can be expected to predict process states accurately. It was found that the model could accurately predict process states of multiple fermentations performed at fixed conditions within the determined validity domain. The results suggest that intraexperimental variations of process conditions could be used to reduce the number of experiments by a factor, which in limit would be equivalent to the number of intraexperimental variations per experiment.

Original languageEnglish
Pages (from-to)1343-1352
Number of pages10
JournalBiotechnology Progress
Volume32
Issue number5
DOIs
Publication statusPublished - 1 Sep 2016

Fingerprint

Feasibility Studies
Fermentation
Escherichia coli
Bioreactors
Biomass
Carbon
Cell Count
Temperature
Proteins

Keywords

  • dynamic excitations
  • hybrid modeling
  • intensified design of experiments
  • PAT
  • QbD
  • upstream bioprocess development/optimization

Cite this

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abstract = "In this study, step variations in temperature, pH, and carbon substrate feeding rate were performed within five high cell density Escherichia coli fermentations to assess whether intraexperiment step changes, can principally be used to exploit the process operation space in a design of experiment manner. A dynamic process modeling approach was adopted to determine parameter interactions. A bioreactor model was integrated with an artificial neural network that describes biomass and product formation rates as function of varied fed-batch fermentation conditions for heterologous protein production. A model reliability measure was introduced to assess in which process region the model can be expected to predict process states accurately. It was found that the model could accurately predict process states of multiple fermentations performed at fixed conditions within the determined validity domain. The results suggest that intraexperimental variations of process conditions could be used to reduce the number of experiments by a factor, which in limit would be equivalent to the number of intraexperimental variations per experiment.",
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Toward intensifying design of experiments in upstream bioprocess development: An industrial Escherichia coli feasibility study. / von Stosch, Moritz; Hamelink, Jan Martijn; Oliveira, Rui.

In: Biotechnology Progress, Vol. 32, No. 5, 01.09.2016, p. 1343-1352.

Research output: Contribution to journalArticle

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