Characterisation of a novel miniaturised bubble column bioreactor for high throughput cell cultivation

A miniature (2 ml) bioreactor has been developed for the high throughput cultivation of microorganisms. The microplate bubble column bioreactor (MBCB) consists of a static deep well microtiter plate with polyethylene frits (pore size 20 μm) inserted into the base of each of the 48 wells. Air was supplied at a controlled flow rate to the underside of each well and in this way the air passing through the pores of the frit formed bubbles in the liquid biomedium. A volumetric mass transfer coefficient for oxygen (kLa) of up to 220 h−1 could be achieved in this novel system. Since the system was not shaken, as is usually required with cell cultivations in microtiter plates, its performance was simpler to model and predict. A miniature optical oxygen probe was used to measure the dissolved oxygen concentration and it was found that the derived kLa values were proportional to the superficial gas velocity over the range 0-0.02 m s−1. The usefulness of this new device was demonstrated by carrying out 25 parallel experiments to optimise the growth conditions of Bacillus subtilis ATCC6633, a strict aerobe, over a range of pH values and C/N ratios.