Bioprocess development is typically performed at laboratory scale conditions, which differ a lot from the conditions at industrial scale, since large scale bioreactors are not ideally mixed and consist of zones with changing environmental conditions. Microbial cells are experiencing changing environmental conditions, such as switches from high and low oxygen supply as well as surplus or depletion of important nutrients. Such effects can be a source of bioprocess performance losses.
Modeling of heterogeneities
The conditions inside a bioreactor vessel can be approached by computational fluid dynamics. The visualization of mixing characteristics and the distribution of nutrients and oxygen give insight into the formation of gradients in the bioreactor. Moreover, computational life lines of single cells can be simulated and the different environmental conditions are analysed taking the cells perspective.
Scale-down bioreactor setup
In order to mimic bioreactor heterogeneity at the laboratory level, the scale-down bioreactor approach can be used. Here, two lab-scale bioreactors are connected and the cells frequently change between the compartments. One compartment represents the well mixed bulk zone of a large bioreactor and the second mimics a disturbance zone and such disturbance could be oxygen depletion or substrate surplus. Such experiments help to evaluate the metabolic robustness for a biological system of bioprocess for scale-up.