Insight into the large-scale upstream fermentation environment using scaled-down models

Scaled‐down models are small‐scale bioreactors, used to mimic the chemical (pH, nutrient and dissolved oxygen) and physical (pressure, viscosity and temperature) gradients known to occur in the large‐scale fermenter. Conventionally, before scaling up any bioprocess, small‐scale bioreactors are used for strain selection, characterisation and optimisation. The typical small‐scale environment is homogenous, hence all the cells held within the small‐scale bioreactor can be assumed to experience the same condition at any point in time. However, for the large‐scale bioreactor, this is not the case, due to its inhomogeneous environment. Three different scaled‐down models are reviewed here, and the results suggest that a bacterium responds to changes in its environment rapidly and the magnitude of response to environmental oscillations is organism‐specific. The reaction and adaption of a bacterium to an inhomogeneous environment in most cases result in productivity and quality losses. This review concludes that consideration of fermentation gradients should be paramount when researchers screen for high yielding mutants in bioprocess development and doing this would help mitigate performance loss on scale‐up.