Small-scale stirred tank reactors for the cultivation of microorganisms with varying morphology

Ralf Hortsch, doctoral thesis Technische Universität München, 2011

The miniaturization and parallelization of bioreactors can help to significantly reduce process development times. A new impeller for parallel milliliter-scale bioreactors was developed that allows the cultivation of microorganisms with varying morphology, which are often used in industrial production processes. The impeller ensures uniform energy dissipation, efficiently prevents wall growth and generates sufficient mass transfer area. Based on an extensive process engineering characterization of the new bioreactors, a reliable and robust scale up of processes is possible. This was demonstrated with the successful production of an antimycotic using the mycelium forming microorganism Streptomyces tendae. The process performances were equivalent with regard to growth, substrate consumption and product formation over a process time of more than 120 h in the milliliter-bioreactors compared to a reference liter-scale bioreactor.

Publications

• Dennewald D, Hortsch R, Weuster-Botz D (2012): Evaluation of parallel millilitre-scale stirred-tank bioreactors for the study of biphasic whole-cell biocatalysis with ionic liquids. J Biotechnol 157: 253-257.
• Gebhardt G, Hortsch R, Kaufmann K, Arnold M, Weuster-Botz D (2011): A new microfluidic concept for parallel operated millilitre-scale stirred-tank bioreactors. Biotechnol Prog 27: 684-690.
• Hortsch R, Weuster-Botz D (2011): Growth and recombinant protein expression with Escherichia coli in different batch cultivation media. Appl Microbiol Biotechnol 90: 69-76.
• Hortsch R, Krispin H, Weuster-Botz D (2010): Process performance of parallel bioreactors for batch cultivation of Streptomyces tendae. Bioproc Biosys Eng, 34: 297-304.
• Hortsch R, Weuster-Botz D (2010): Milliliter-scale stirred tank reactors for the cultivation of microorganisms. Adv Appl Microbiol 73: 61-82.
• Hortsch R, Stratmann A, Weuster-Botz D (2010): New milliliter-scale stirred tank bioreactors for the cultivation of mycelium forming microorganisms. Biotechnol Bioeng 106: 443-451.
• Hortsch R, Weuster-Botz D (2010): Power consumption and maximum energy dissipation in a milliliter-scale bioreactor. Biotechnol Prog 26: 595-599.