Design of a prototype miniature bioreactor for high throughput automated bioprocessing

Abstract

A new miniature bioreactor with a diameter equal to that of a single well of a 24-well plate is described and its engineering performance as a fermenter assessed. Mixing in the miniature bioreactor is provided by a set of three impellers mechanically driven via a microfabricated electric motor and aeration is achieved with a single tube sparger. Parameter sensitive fluorophors are used with fibre optic probes for continuous monitoring of dissolved oxygen tension and an optical based method is employed to monitor cell biomass concentration during fermentation. Experimental measurements are provided on volumetric mass transfer coefficient for air–water and bacterial fermentation data are presented for Escherichia coli. The local and average power input, energy dissipation rate and bubble size are derived from an analysis of the multiphase flow in the miniature bioreactor using computational fluid dynamics (CFD). Volumetric mass transfer coefficients are predicted using Higbie's penetration model with the contact time obtained from the CFD simulations of the turbulent flow in the bioreactor. Comparative data are provided from parallel experiments carried out in a 20 l (15 l working volume) conventional fermenter. Predicted and measured volumetric mass transfer coefficients in the miniature bioreactor are in the range 100–400 h−1, typical of those reported for large-scale fermentation.