Simulation and Optimization of Essential Amino Acids in Dynamic Mammalian Cell Culture

  • Carolyn M. C. Lam
  • Alexandros Kiparissides
  • Danny C.F. Wong
  • Miranda G.S. Yap
  • Efstratios N. Pistikopoulos
  • Athanasios Mantalaris
Conference paper
Part of the ESACT Proceedings book series (ESACT, volume 5)

Abstract

Optimization in mammalian cell culture systems is currently exclusively experimental, which is an expensive and time-consuming process. Mathematical models have become established practice in many process industries. Herein, a systematic framework has been developed that allows the simulation and off-line optimization of fed-batch monoclonal antibody-producing hybridoma cell cultures. The model describes major cellular functions as well as the uptake of amino acids and how it affects growth and productivity. The model-based optimization approach was able to provide an estimation of the optimal dynamic profile of essential amino acids in order to improve the IFNγ yield.

Keywords

Essential Amino Acid Dynamic Optimization Mammalian Cell Culture Global Sensitivity Analysis Model Amino Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We would like to thank Dr. Sergei Kucherenko for his help with the GSA analysis and the Hutchinson-Whampoa BBSRC Dorothy Hodgkin Postgraduate Award for supporting this research.

References

  1. Frahm B, Lane P, Markl H, Portner R (2003) Improvement of a mammalian cell culture process by adaptive, model-based dialysis fed-batch cultivation and suppression of apoptosis. Bioprocess Biosyst Eng 26:1–10.PubMedCrossRefGoogle Scholar
  2. Kiparissides A, Kucherenko S, Mantalaris A, Pistikopoulos EN (2009) Global Sensitivity Analysis Challenges in Biological Systems Modeling. Ind Eng Chem Res 48(15):7168–7180.CrossRefGoogle Scholar
  3. Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22:1393–1398.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Carolyn M. C. Lam
    • 1
  • Alexandros Kiparissides
    • 1
  • Danny C.F. Wong
    • 2
  • Miranda G.S. Yap
    • 4
    • 3
  • Efstratios N. Pistikopoulos
    • 1
  • Athanasios Mantalaris
    • 1
  1. 1.Department of Chemical EngineeringCentre for Process Systems Engineering, Imperial College LondonLondonUK
  2. 2.Bioprocessing Technology Institute, Agency for Science and Technology Research (A*STAR)CentrosSingapore
  3. 3.Singapore-MIT AllianceNational University of SingaporeSingaporeSingapore
  4. 4.Bioprocessing Technology Institute, Agency for Science and Technology Research (A*STAR)CentrosSingapore

Personalised recommendations