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Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
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Updated: May 30, 2026

Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology
06:24

Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology

Published on: December 15, 2017

Improving cultivation processes for recombinant protein production.

A Kuprijanov1, S Schaepe, M Aehle

  • 1Center for Bioprocess Engineering, Martin-Luther-University Halle Wittenberg, Kurt-Mothes-Straße 3, Halle/Saale, Germany.

Bioprocess and Biosystems Engineering
|July 23, 2011
PubMed
Summary

A new cascade control system enhances recombinant protein production by precisely managing carbon dioxide levels and biomass growth. This improves batch-to-batch consistency in fed-batch cultivations, offering a reliable alternative to complex controllers.

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Area of Science:

  • Biotechnology
  • Process Engineering
  • Bioprocess Control

Background:

  • Recombinant protein production relies on stable and reproducible fermentation processes.
  • Existing control strategies often struggle with long response times and process variability.
  • Enhanced control is crucial for optimizing yield and consistency in biomanufacturing.

Purpose of the Study:

  • To introduce and validate a novel cascade control system for bioprocess cultivation.
  • To improve batch-to-batch reproducibility in fed-batch fermentation.
  • To provide a simple yet effective control alternative for biopharmaceutical production.

Main Methods:

  • Design and tuning of a cascade control system using a virtual plant environment (SIMATIC PCS 7).
  • Direct control of carbon dioxide production rate and mass.
  • Simultaneous regulation of specific biomass growth rates and biomass profiles.
  • Validation through experimental application in Escherichia coli and CHO cell cultures.

Main Results:

  • The cascade control system demonstrated superior performance compared to previous methods in simulations and experiments.
  • Significant improvement in batch-to-batch reproducibility of fermentation processes was achieved.
  • The controller effectively managed processes with long response times and delays.
  • Successful application in both bacterial (E. coli) and mammalian (CHO) cell cultures.

Conclusions:

  • The presented cascade control system offers a robust and reproducible method for managing fed-batch cultivations.
  • It provides a straightforward and reliable alternative to complex model-supported controllers.
  • This approach enhances process consistency and is suitable for various biopharmaceutical production systems.