Disposable Bioreactors pp 33-53

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

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
Chapter

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.

Keywords

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

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

References

  1. 1.
    Wurm FM (2004) Nat Biotechnol 22:1393CrossRefGoogle Scholar
  2. 2.
    Büchs J (2001) Biochem Eng J 7:91CrossRefGoogle Scholar
  3. 3.
    Liu C, Hong L (2001) Biochem Eng J 7:121CrossRefGoogle Scholar
  4. 4.
    De Jesus MJ, Girard P, Bourgeois M, Baumgartner G, Jacko B, Amstutz H, Wurm FM (2004) Biochem Eng J 17:217CrossRefGoogle Scholar
  5. 5.
    Muller N, Girard P, Hacker DL, Jordan M, Wurm FM (2005) Biotechnol Bioeng 89:400CrossRefGoogle Scholar
  6. 6.
    Micheletti M, Barrett T, Doig SD, Bagany F, Levy MS, Woodley JM, Lye GJ (2006) Chem Eng Sci 61:2939CrossRefGoogle Scholar
  7. 7.
    Muller N, Derouazi M, Van Tilborgh F, Wulhfard S, Hacker DL, Jordan M, Wurm FM (2007) Biotechnol Lett 29:703CrossRefGoogle Scholar
  8. 8.
    Stettler M, Zhang XW, Hacker DL, DeJesus MD, Wurm FM (2007) Biotech Prog 23:1340CrossRefGoogle Scholar
  9. 9.
    D’Aquino R (2006) Chem Eng Prog 102:8Google Scholar
  10. 10.
    Girard P, Jordan M, Tsao M, Wurm FM (2001) Biochem Eng J 7:117CrossRefGoogle Scholar
  11. 11.
    Stettler M, De Jesus M, Ouertatani H, Engelhardt E-M, Muller N, Chenuet S, Bertschinger M, Baldi L, Hacker D, Jordan M, Wurm FM (2007) 1,000 non-instrumented bioreactors in a week. In: Smith R (ed.) Cell technology for cell products. Springer, Dordrecht, The NetherlandsGoogle Scholar
  12. 12.
    Derouazi M, Girard P, Van Tilborgh F, Iglesias K, Muller N, Bertschinger M, Wurm FM (2004) Biotechnol Bioeng 87:537CrossRefGoogle Scholar
  13. 13.
    Stettler M, Jaccard N, Hacker D, DeJesus M, Wurm FM, Jordan M (2006) Biotechnol Bioeng 95:1228–1233CrossRefGoogle Scholar
  14. 14.
    Pham PL, Perret S, Doan HC, Cass B, St-Laurent G, Kamen A, Durocher Y (2003) Biotechnol Bioeng 84:332–342.CrossRefGoogle Scholar
  15. 15.
    Pham PL, Perret S, Cass B, Carpentier E, St-Laurent G, Bisson L, Kamen A, Durocher Y (2005) Biotechnol Bioeng 90:332CrossRefGoogle Scholar
  16. 18.
    Krahe M (2002) Biochemical Engineering. In: Ullmann’s Encyclopedia of Industrial Chemistry. 6th Edition. pp. 171-240. Wiley-VCH Verlag GmbH & Co., Weinheim, GermanyGoogle Scholar
  17. 17.
    Maier U, Büchs J (2001) Biochem Eng J 7:99CrossRefGoogle Scholar
  18. 18.
    Zhang H, Williams-Dalson W, Keshavarz-Moore E, Shamlou PA (2005) Biotechnol Appl Biochem 41:1–8CrossRefGoogle Scholar
  19. 19.
    Deshpande RR, Heinzle E (2004) Biotechnol Lett 26:763CrossRefGoogle Scholar
  20. 20.
    Deshpande RR, Koch-Kirsch Y, Maas R, John GT, Krause C, Heinzle E 2005) Assay Drug Dev Technol 3:299CrossRefGoogle Scholar
  21. 21.
    Kensy F, Zimmermann HF, Knabben I, Anderlei T, Trauthwein H, Dingerdissen U, Büchs J (2005) Biotechnol Bioeng 89:698CrossRefGoogle Scholar
  22. 22.
    Gupta A, Rao G (2003) Biotechnol Bioeng 84:351CrossRefGoogle Scholar
  23. 23.
    Wittmann C, Kim HM, John G, Heinzle E (2003) Biotechnol Lett 25:377CrossRefGoogle Scholar
  24. 24.
    Amoabediny G, Büchs J (2007) Biotechnol Appl Biochem 46:57CrossRefGoogle Scholar
  25. 25.
    John GT, Klimant I, Wittmann C, Heinzle E (2003) Biotechnol Bioeng 81:829CrossRefGoogle Scholar
  26. 26.
    Suijdam JCV, Kossen NWF, Joha AC (1978) Biotechnol Bioeng 20:1695CrossRefGoogle Scholar
  27. 27.
    Hermann R, Lehmann M, Büchs J (2003) Biotechnol Bioeng 81:178CrossRefGoogle Scholar
  28. 28.
    Marks DM (2003) Cytotechnology 42:21CrossRefGoogle Scholar
  29. 29.
    Raval K, Liu C, Büchs J (2006) BioProcess Int 4:46Google Scholar
  30. 30.
    Kato Y, Peter CP, Akgün A, Büchs J (2004) Biochem Eng J 21:83CrossRefGoogle Scholar
  31. 31.
    Nikakhtari H, Hill G (2005) Can J Chem Eng 83:493CrossRefGoogle Scholar
  32. 32.
    Büchs J, Maier U, Lotter S, Peter CP (2007) Biochem Eng J 34:200CrossRefGoogle Scholar
  33. 33.
    Peter PC, Suzuki Y, Buchs J (2006) Biotech Bioeng 93:1164CrossRefGoogle Scholar
  34. 34.
    Varley J, Birch J (1999). Cytotechnology 29:177CrossRefGoogle Scholar
  35. 35.
    Morrow J (2006) GEN 26:52Google Scholar
  36. 36.
    Senger RS, Karim MN (2003) Biotechnol Prog 19:1199CrossRefGoogle Scholar

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

Personalised recommendations