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Use of Orbital Shaken Disposable Bioreactors for Mammalian Cell Cultures from the Milliliter-Scale to the 1,000-Liter Scale

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Disposable Bioreactors

Part of the book series: Advances in Biochemical Engineering / Biotechnology ((ABE,volume 115))

Abstract

Driven by the commercial success of recombinant biopharmaceuticals, there is an increasing demand for novel mammalian cell culture bioreactor systems for the rapid production of biologicals that require mammalian protein processing. Recently, orbitally shaken bioreactors at scales from 50 mL to 1,000 L have been explored for the cultivation of mammalian cells and are considered to be attractive alternatives to conventional stirred-tank bioreactors because of increased flexibility and reduced costs. Adequate oxygen transfer capacity was maintained during the scale-up, and strategies to increase further oxygen transfer rates (OTR) were explored, while maintaining favorable mixing parameters and low-stress conditions for sensitive lipid membrane-enclosed cells. Investigations from process development to the engineering properties of shaken bioreactors are underway, but the feasibility of establishing a robust, standardized, and transferable technical platform for mammalian cell culture based on orbital shaking and disposable materials has been established with further optimizations and studies ongoing.

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Notes

  1. 1.

    Richard August Carl Emil Erlenmeyer (28 June 1825–22 January 1909): He studied at Gießen under Justus von Liebig and at Heidelberg under Friedrich Kekulé. He also associated himself with Robert Bunsen in the study of fertilizers. Erlenmeyer was professor of chemistry at the Munich Polytechnic School from 1868 to 1883. His experimental work included the discovery and synthesis of several organic compounds, e.g., isobutyric acid (1865); in 1861 he invented the conical flask that bears his name. Among the first to adopt structural formulas based on valence, he proposed the modern naphthalene formula of two benzene rings sharing two carbon atoms.

  2. 2.

    2 The 50-mL shake tubes with filter cap originally sold under the name TubeSpin®-bioreactors (Techno Plastic Products AG, Trasadingen, Switzerland) are also available under the tradename CultiFlask 50 Tube by Sartorius Stedim AG (Göttingen, Germany). A second generation CultiFlask 50 tube with a modified geometry is expected to be released soon.

  3. 3.

    The DO was 6.72 mg L −1 at 37°C, assuming normal pressure conditions (1,013 mbar).

Abbreviations

CFD:

Computational fluid dynamics

CHO:

Chinese hamster ovary

DO:

Dissolved oxygen

HEK:

Human embryonic kidney

OTR:

Oxygen transfer rate

PCV:

Packed cell volume

SIP:

sterilization in place

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Author information

Authors and Affiliations

  1. Laboratory of Cellular Biotechnology, École Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland

    Xiaowei Zhang, Matthieu Stettler, David Hacker & Florian Wurm

  2. Chair of Modelling and Scientific Computing, École Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland

    Dario De Sanctis, Marco Perrone, Nicola Parolini, Marco Discacciati & Alfio Quarteroni

  3. ExcellGene SA, CH-1870, Monthey, Switzerland

    Maria De Jesus & Florian Wurm

Authors
  1. Xiaowei Zhang
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  2. Matthieu Stettler
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  3. Dario De Sanctis
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  4. Marco Perrone
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  5. Nicola Parolini
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  6. Marco Discacciati
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  7. Maria De Jesus
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  8. David Hacker
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  9. Alfio Quarteroni
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  10. Florian Wurm
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Corresponding author

Correspondence to Florian Wurm .

Editor information

Editors and Affiliations

  1. Hochschule Wädenswil, Wädenswil, Switzerland

    Regine Eibl

  2. Hochschule Wädenswil, Wädenswil, Switzerland

    Dieter Eibl

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© 2009 Springer-Verlag Berlin Heidelberg

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Zhang, X. et al. (2009). Use of Orbital Shaken Disposable Bioreactors for Mammalian Cell Cultures from the Milliliter-Scale to the 1,000-Liter Scale. In: Eibl, R., Eibl, D. (eds) Disposable Bioreactors. Advances in Biochemical Engineering / Biotechnology, vol 115. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2008_18

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