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Advanced microscale bioreactor system: a representative scale-down model for bench-top bioreactors

Abstract

In recent years, several automated scale-down bioreactor systems have been developed to increase efficiency in cell culture process development. ambr™ is an automated workstation that provides individual monitoring and control of culture dissolved oxygen and pH in single-use, stirred-tank bioreactors at a working volume of 10–15 mL. To evaluate the ambr™ system, we compared the performance of four recombinant Chinese hamster ovary cell lines in a fed-batch process in parallel ambr™, 2-L bench-top bioreactors, and shake flasks. Cultures in ambr™ matched 2-L bioreactors in controlling the environment (temperature, dissolved oxygen, and pH) and in culture performance (growth, viability, glucose, lactate, Na+, osmolality, titer, and product quality). However, cultures in shake flasks did not show comparable performance to the ambr™ and 2-L bioreactors.

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Acknowledgments

The authors thank cell line development groups for generating the CHO cell lines evaluated; B6 media preparation group for supplying all the media and solutions used; cell banking group for supplying ampoules; Peter Harms and Louis Cheung for discussions on methods of higher throughput for off-line analysis; Analytical Operations group, especially Yun Tang, Kevin Lin, and Renee Yang, for providing analytical support for titer, product quality and amino acid assays; Andy Lin and John Joly for guidance and support.

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Correspondence to Wei-Ting Hsu.

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Hsu, WT., Aulakh, R.P.S., Traul, D.L. et al. Advanced microscale bioreactor system: a representative scale-down model for bench-top bioreactors. Cytotechnology 64, 667–678 (2012). https://doi.org/10.1007/s10616-012-9446-1

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  • DOI: https://doi.org/10.1007/s10616-012-9446-1

Keywords

  • Scale-down system
  • Chinese hamster ovary
  • Cell culture automation
  • ambr™
  • Single-use bioreactor