In the biopharmaceutical industry, accurate prediction of the oxygen
uptake rate (OUR) by the cells is critical to understanding cell health.
Accurate estimation of the oxygen transfer rate (OTR) presents a
significant challenge in predicting OUR, and OTR is dependent on the
volumetric oxygen mass transfer coefficient (kLa). Often
kLa is assumed to be constant throughout a fermentation
and estimated from experiments using no cells and in a buffer solutions.
Yet, it is well-known that additions (i.e., glucose, base, and
antifoam), cell secretions, and stir speed markedly effect
kLa. Currently, there are three standard methods used to
estimate kLa; however, all three have significant
issues. This rapid communication describes a novel, non-disruptive
method to estimate kLa by modulating the gas flow rate.
This approach allowed accurate kLa estimates at multiple
times throughout Escherichia coli batch fermentations using a
non-disruptive technique, thus lowering the risk of losing a
fermentation due to inadequate oxygenation.