Miniaturized parallel bioreactors for high-throughput bioprocess design

Robert Puskeiler, doctoral thesis Technische Universität München, 2004

To enable more effective bioprocess design, a milliliter-scale bioreactor equipped with a gas-inducing impeller was developed. The sorption characteristics of this novel, magnetic-inductive stirring system allows for oxygen transfer coefficients of more than 0.4 1/s. Up to 48 milliliter-scale bioreactors can be operated in a reaction block. A sterile barrier permits the maintenance of monoseptic conditions. A liquid-handling system was used for fed-batch operation, titration of pH, automatic sampling and automated atline analytics. Growth of Escherichia coli in a pH-controlled fed-batch corresponded to a reference cultivation in a lab-scale stirred-tank reactor. Within 21 h process time, a dry cell weight concentration of 24 g/L was reached.


  • Weuster-Botz D, Hekmat D, Puskeiler R, Franco-Lara E (2007): Enabling Technologies: Fermentation and Downstream Processing. Adv Biochem Eng Biotechnol 105: 205-247.
  • Puskeiler R, Weuster-Botz D (2005): Combined sulfite method for the measurement of the oxygen transfer coefficient kLa in bioreactors. J Biotechnol 120: 430-438.
  • Weuster-Botz D, Puskeiler R, Kusterer A, Kaufmann K, John GT, Arnold M (2005): Methods and milliliter scale devices for high-throughput bioprocess design. Bioprocess Biosyst Eng 28: 109-119.
  • Puskeiler R, Kusterer A, John GT, Weuster-Botz D (2005): Miniature bioreactors for automated high-throughput bioprocess design (HTBD): reproducibility of parallel fed-batch cultivations with Escherichia coli. Biotechnol Appl Biochem 42: 227-235.
  • Puskeiler R, Kaufmann K, Weuster-Botz D (2005): Development, parallelization, and automation of a gas-inducing milliliter-scale bioreactor for high-throughput bioprocess design (HTBD). Biotechnol Bioeng 89: 512-523.