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

  • Xiaowei Zhang
  • Matthieu Stettler
  • Dario De Sanctis
  • Marco Perrone
  • Nicola Parolini
  • Marco Discacciati
  • Maria De Jesus
  • David Hacker
  • Alfio Quarteroni
  • Florian Wurm
Part of the Advances in Biochemical Engineering / Biotechnology book series (ABE, volume 115)


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.


Disposable bioreactor Mammalian cell culture Orbital shaking Oxygen transfer rate Scale-up Shaken bioreactor 



Computational fluid dynamics


Chinese hamster ovary


Dissolved oxygen


Human embryonic kidney


Oxygen transfer rate


Packed cell volume


sterilization in place


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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Xiaowei Zhang
    • 1
  • Matthieu Stettler
    • 1
  • Dario De Sanctis
    • 2
  • Marco Perrone
    • 2
  • Nicola Parolini
    • 2
  • Marco Discacciati
    • 2
  • Maria De Jesus
    • 3
  • David Hacker
    • 1
  • Alfio Quarteroni
    • 2
  • Florian Wurm
    • 1
    • 3
  1. 1.Laboratory of Cellular BiotechnologyÉcole Polytechnique Fédérale de LausanneLausanneSwitzerland
  2. 2.Chair of Modelling and Scientific ComputingÉcole Polytechnique Fédérale de LausanneLausanneSwitzerland
  3. 3.ExcellGene SAMontheySwitzerland

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