Scale-down of microbial processes

A multidimensional approach is used to identify suitable scale-down workflows to mimic and subsequently optimize laboratory-scale industrial bioprocesses. The effects of different scale-down configurations on cultivation performance are compared to industrial cultivation with a focus on the oleogenic yeast Yarrowia lipolytica and single-cell analysis of its macromorphology and lipid droplet formation. This concept is followed up to the industrial production scale.
With advanced in-situ microscopy, macromorphological changes to elongated cells, a sign for cell stress, can be measured with sufficient time and size resolution. This allows a better assignment of occurring macromorphological changes to specific cultivation conditions, including scale-up effects.

In general, so far a greater agreement between population heterogeneities across scales was found with multi-compartment systems than with single-compartment systems. Overall, oscillatory conditions have effects on product formation behavior and amino acid incorporation in Yarrowia lipolytica in this regard. Interestingly, the addition of complex components in the medium does not lead to a noticeable improvement of resistance against typical scale-related stress factors.