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Orbitally Shaken Single-Use Bioreactor for Animal Cell Cultivation: Fed-Batch and Perfusion Mode

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Animal Cell Biotechnology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2095))

Abstract

Increasing the cultivation volume from small to large scale can be a rather complex and challenging process when the method of aeration and mixing is different between scales. Orbitally shaken bioreactors (OSBs) utilize the same hydrodynamic principles that define the success of smaller-scale cultures, which are developed on an orbitally shaken platform, and can simplify scale-up. Here we describe the basic working principles of scale-up in terms of the volumetric oxygen transfer coefficient (kLa) and mixing time and how to define these parameters experimentally. The scale-up process from an Erlenmeyer flask shaken on an orbital platform to an orbitally shaken single-use bioreactor (SB10-X, 12 L) is described in terms of both fed-batch and perfusion-based processes. The fed-batch process utilizes a recombinant variant of the mammalian cell line, Chinese hamster ovary (CHO), to express a biosimilar of a therapeutic monoclonal antibody. The perfusion-based process utilizes either an alternating tangential flow filtration (ATF) or a tangential flow filtration (TFF) system for cell retention to cultivate an avian cell line, AGE1.CR.pIX, for the propagation of influenza A virus, H1N1, in high cell density. Based on two example cell cultivations, processes outline the advantages that come with using an orbitally shaken bioreactor for scaling-up a process. The described methods are also applicable to other suspension cell lines.

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Acknowledgments

The authors thank V. Sandig (ProBioGen AG) for kindly providing the AGE1.CR.pIX cell line and I. Behrendt (MPI Magdeburg) for the excellent technical work.

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Authors and Affiliations

  1. Adolf Kühner AG, Birsfelden, Switzerland

    Tim Bürgin & Tibor Anderlei

  2. Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany

    Juliana Coronel, Yvonne Genzel & Udo Reichl

  3. HES-SO University of Applied Sciences and Arts Western Switzerland, Sion, Switzerland

    Gerrit Hagens

  4. Kuhner Shaker Inc., San Carlos, CA, USA

    Michael V. Keebler

Authors
  1. Tim Bürgin
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  2. Juliana Coronel
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  3. Gerrit Hagens
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  4. Michael V. Keebler
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  5. Yvonne Genzel
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  6. Udo Reichl
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  7. Tibor Anderlei
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Corresponding author

Correspondence to Tim Bürgin .

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Editors and Affiliations

  1. Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology (TUHH), Hamburg, Germany

    Ralf Pörtner

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Bürgin, T. et al. (2020). Orbitally Shaken Single-Use Bioreactor for Animal Cell Cultivation: Fed-Batch and Perfusion Mode. In: Pörtner, R. (eds) Animal Cell Biotechnology. Methods in Molecular Biology, vol 2095. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0191-4_7

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  • DOI: https://doi.org/10.1007/978-1-0716-0191-4_7

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0190-7

  • Online ISBN: 978-1-0716-0191-4

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