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Turbidimetry and Dielectric Spectroscopy as Process Analytical Technologies for Mammalian and Insect Cell Cultures

  • Lukas Käßer
  • Jan Zitzmann
  • Tanja Grein
  • Tobias Weidner
  • Denise Salzig
  • Peter CzermakEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2095)

Abstract

The production of biopharmaceuticals in cell culture involves stringent controls to ensure product safety and quality. To meet these requirements, quality by design principles must be applied during the development of cell culture processes so that quality is built into the product by understanding the manufacturing process. One key aspect is process analytical technology, in which comprehensive online monitoring is used to identify and control critical process parameters that affect critical quality attributes such as the product titer and purity. The application of industry-ready technologies such as turbidimetry and dielectric spectroscopy provides a deeper understanding of biological processes within the bioreactor and allows the physiological status of the cells to be monitored on a continuous basis. This in turn enables selective and targeted process controls to respond in an appropriate manner to process disturbances. This chapter outlines the principles of online dielectric spectroscopy and turbidimetry for the measurement of optical density as applied to mammalian and insect cells cultivated in stirred-tank bioreactors either in suspension or as adherent cells on microcarriers.

Key words

Process analytical technology Online process monitoring Optical density Dielectric spectroscopy Drosophila melanogaster S2 cells Vero cells Measles virus Cell cultivation 

Notes

Acknowledgments

We thank the Federal Ministry of Education and Research (BMBF) for financial support (Grant No. 13FH001IX5), the Hessen State Ministry of Higher Education, Research and the Arts for financial support within the Hessen initiative for scientific and economic excellence (LOEWE Center for Insect Biotechnology and Bioresources), and Richard M. Twyman for professional editing of the manuscript.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Lukas Käßer
    • 1
  • Jan Zitzmann
    • 1
  • Tanja Grein
    • 1
  • Tobias Weidner
    • 1
  • Denise Salzig
    • 1
  • Peter Czermak
    • 1
    • 2
    • 3
    Email author
  1. 1.Institute of Bioprocess Engineering and Pharmaceutical Technology (IBPT)Technische Hochschule Mittelhessen (THM)—University of Applied SciencesGiessenGermany
  2. 2.Faculty of Biology and ChemistryJustus-Liebig-University GiessenGiessenGermany
  3. 3.Division BioresourcesFraunhofer Institute for Molecular Biology and Applied Ecology (IME)GiessenGermany

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