Does the BioBLU 0.3f single-use scale to the BioFlo® 320 reuseable bioreactor on a matched volumetric oxygen mass transfer coefficient?

The volumetric oxygen mass transfer coefficient ([Formula: see text]) is an essential parameter in aerobic high-cell density fermentation where the availability of oxygen to growing microorganisms is a limiting factor. Bioprocess teams looking to scale-up/down between the Eppendorf BioBLU 0.3f single-use vessel and the BioFlo® 320 reusable vessel bioreactors may find it challenging using a matched [Formula: see text]. The maximum [Formula: see text] of the BioFlo® 320 reusable bioreactor was 109 h-1, which was approximately twice that of the BioBLU 0.3f single-use vessel. The results here show no overlap in [Formula: see text] values when both bioreactors were compared and thus conclude that scalability based on [Formula: see text] is not viable. The maximum [Formula: see text] of the Eppendorf BioBLU 0.3f single-use reported here was 47 h-1 compared to that of the manufacturer's value of 2500 h-1, indicating a 53-fold difference. This discrepancy was attributed to the incompatible sulfite addition method used by the manufacturer for estimation.

Scale-down studies for the scale-up of a recombinant Corynebacterium glutamicum fed-batch fermentation: loss of homogeneity leads to lower levels of cadaverine production.

BACKGROUND: The loss of efficiency and performance of bioprocesses on scale-up is well known, but not fully understood. This work addresses this problem, by studying the effect of some fermentation gradients (pH, glucose and oxygen) that occur at the larger scale in a bench-scale two-compartment reactor [plug flow reactor (PFR) + stirred tank reactor (STR)] using the cadaverine-producing recombinant Corynebacterium glutamicum DM1945 Δact3 Ptuf-ldcC_OPT. The new scale-down strategy developed here studied the effect of increasing the magnitude of fermentation gradients by considering not only the average cell residence time in the PFR (τ PFR), but also the mean frequency at which the bacterial cells entered the PFR (f m) section of the two-compartment reactor. RESULTS: On implementing this strategy the cadaverine production decreased on average by 26%, 49% and 59% when the τ PFR was increased from 1 to 2 min and then 5 min respectively compared to the control fermentation. The carbon dioxide productivity was highest (3.1-fold that of the control) at a τ PFR of 5 min, but no losses were observed in biomass production. However, the population of viable but non-culturable cells increased as the magnitude of fermentation gradients was increased. The new scale-down approach was also shown to have a bigger impact on fermentation performance than the traditional one. CONCLUSION: This study demonstrated that C. glutamicum DM1945 Δact3 Ptuf-ldcC_OPT physiological response was a function of the magnitude of fermentation gradients simulated. The adaptations of a bacterial cell within a heterogeneous environment ultimately result in losses in fermentation productivity as observed here. © 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.