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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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Process Optimization using High Throughput Automated Micro-Bioreactors in Chinese Hamster Ovary Cell Cultivation
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On-line multiple component analysis for efficient quantitative bioprocess development.

Christian Dietzsch1, Oliver Spadiut, Christoph Herwig

  • 1Vienna University of Technology, Institute of Chemical Engineering, Research Area Biochemical Engineering, Vienna, Austria.

Journal of Biotechnology
|April 10, 2012
PubMed
Summary

This study introduces a novel on-line monitoring device for real-time bioprocess analysis. The system ensures high data quality, enabling accurate quantification and physiological insights for Pichia pastoris cultivations.

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Published on: May 11, 2017

Area of Science:

  • Biotechnology
  • Process Analytical Technology (PAT)
  • Microbial Cultivation

Background:

  • Accurate on-line monitoring is crucial for rapid bioprocess quantification.
  • Real-time data quality assessment is essential for reliable quantitative information extraction.
  • Existing methods may lack the precision and automation required for comprehensive bioprocess analysis.

Purpose of the Study:

  • To characterize a novel on-line sampling and analysis device for bioprocess monitoring.
  • To evaluate the device's performance in real-time measurement of multiple components during Pichia pastoris cultivation.
  • To demonstrate the utility of high-quality on-line data for bioprocess understanding and control.

Main Methods:

  • Development and implementation of an automated photometric robot for on-line sampling and analysis.
  • Connection of the on-line device to a bioreactor for Pichia pastoris batch cultivations.
  • Concomitant measurement of six key components: glucose, glycerol, ethanol, acetate, phosphate, and ammonium.

Main Results:

  • On-line measurements showed no significant deviation compared to off-line samples, confirming data accuracy.
  • Calculated on-line rates and yields accurately reflected Pichia pastoris physiological responses.
  • Integration with off-line biomass data enabled detailed analysis of specific rates and cellular physiology.

Conclusions:

  • The novel on-line device provides high-quality, real-time data for bioprocess monitoring.
  • This technology is a valuable tool for Process Analytical Technology (PAT), enhancing bioprocess understanding.
  • Accurate on-line data facilitates precise rate and yield calculations, crucial for optimizing microbial cultivations.