ABSTRACT
Scale-down of bioreactors to the range of microliters or milliliters favors obtaining optimal results at production process conditions. Nevertheless, there is a lack of understanding about the impact of scale-down of some multiphase bioreactors on transport phenomena and kinetics, which has delayed its successful implementation today. This work aims to evaluate the effect of the scale-down on hydrodynamics, mass transfer, and bioconversion in a stirred tank multiphase partitioning bioreactor where the oxidation of bicyclic ketone bicyclo[3.2.0]hept-2-to-6-one to bicyclic lactone (1S,5R)-(−)-2-oxabiciclo[3.3.0]oct-6-en-3-ona is catalyzed on whole cells of Escherichia coli strain TOP10 pQR239. Well-accepted scale-down criteria, based on geometric and dynamic similitude, are applied to this bioreactor under three different reactor volumes, 1000, 100, and 10 mL. To identify factors influencing the product yield, hydrodynamics and mass transfer under abiotic conditions were examined in the three scales using a full face-centered central composite experimental design. Criteria tested might have failed to scale-down a multiphase bioreactor as a consequence of the inadequate consideration in the three scales of viscous and interfacial forces on mass transfer. Based on this, the establishment of new criteria involving multiphase reactions but focusing on hydrodynamics is mandatory to scale-down a multiphase reactor.
