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Scale-down Bioreactor Facility

10L Scale-down reactor: all compartments are sterilizable. Fifteen ports at each plug flow module allow a distinct sampling and monitoring of conditions.

The fed-batch technique is the most frequently applied operation mode for an efficient biotechnological production. Feed addition leads usually to severe concentration gradients of substrate and other additives, oxygen and carbon dioxide in industrial-scale bioreactors. For example, dissolved oxygen becomes limited when substrate concentrations are increased near the feeding point. Hence, cells are opposed to oscillating conditions: from zones with substrate excess and limiting oxygen availability to zones with oxygen excess, but no substrate availability.

The following aspects are focused in research:

  • How can conditions in industrial scale be mimicked in lab scale?
  • How do cells respond to an oscillating environment?
  • What are consequences for strain and process engineering?


In order to observe the behavior of cells at these production conditions, a multi-compartment scale-down reactor concept is applied (fig. beside). It consists of one or several plug flow reactor modules, which are connected to a traditional stirred tank bioreactor.

Currently, the response of Escherichia coli, Corynebacterium glutamicum and Saccharomyces cerevisiae, which are opposed to oscillating conditions in a scale-down bioreactor is observed with several analytical tools for metabolome analysis, cell physiology and morphology:


  • on line electrooptical monitoring and laser-based single-cell size analysis
  • 3-dimensional holographic microcopy
  • metabolome analysis (main carbon metabolites, amino and fatty acids, sterols and nucleotides)
  • flow cytometry
  • metabolic flux analysis

Rapid sampling unit BioScope (TU Delft) for the observation of responses to perturbations in the sec.-scale.

The rapid sampling device BioScope (TU Delft) is applied in combination with scale-down cultivations in order to investigate the impact of oscillating conditions on the fast response of cells to a sudden substrate excess. In this approach, labeling experiments and other techniques are applied, bridging the gap between process development and traditional systems biology approaches.

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Dr.-Ing. Stefan Junne
+49 30 314 72527
Room 261