Methods and milliliter scale devices for high-throughput bioprocess design

Dirk Weuster-Botz, Robert Puskeiler, Andreas Kusterer, Klaus Kaufmann, Gernot T. John, Matthias Arnold

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Based on electromagnetic simulations as well as on computational fluid dynamics simulations gas-inducing impellers and their magnetic inductive drive were optimized for stirred-tank reactors on a 10 ml-scale arranged in a bioreaction block with 48 bioreactors. High impeller speeds of up to 4,000 rpm were achieved at very small electrical power inputs (63 W with 48 bioreactors). The maxima of local energy dissipation in the reaction medium were estimated to be up to 50 W L-1 at 2,800 rpm. Total power input and local energy dissipation are thus well comparable to standard stirred-tank bioreactors. A prototype fluorescence reader for 8 bioreactors with immobilized fluorometric sensor spots was applied for online measurement of dissolved oxygen concentration making use of the phase detection method. A self-optimizing scheduling software was developed for parallel control of 48 bioreactors with a liquid-handling system for automation of titration and sampling. It was shown on the examples of simple parallel batch cultivations of Escherichia coli with different media compositions that high cell densities of up to 16.5 g L -1 dry cell mass can be achieved without pH-control within 5 h with a high parallel reproducibility (standard deviation < 3.5%, n = 48) due to the high oxygen transfer capability of the gas-inducing stirred-tank bioreactors.

Original languageEnglish
Pages (from-to)109-119
Number of pages11
JournalBioprocess and Biosystems Engineering
Volume28
Issue number2
DOIs
StatePublished - Nov 2005

Keywords

  • Automation
  • Bioprocess development
  • Escherichia coli
  • Microorganisms
  • Parallel stirred-tank bioreactors

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