Mixing performance in a litre-scale rocking disposable bioreactor: DoE-based investigation of mixing time dependence on operational parameters

Abstract

• Study on mixing time in disposable bioreactor by sensor method and DoE-methodology. • Mixing time in a 2-litre disposable container ranges from 3 to 1350 s. • Mixing intensity influenced by rocking angle, frequency, and the volume of liquid. • Correlation based on dimensionless terms predicts t 95% for vessels of various sizes. • A step towards the better systematization of liquid flow inside rocking bioreactors. Rocking single-use bioreactors (SUBs) adopt an effective mixing mechanism based on the rocking movement of a platform on which a disposable bag-like container is placed. Non-typical liquid flow patterns make the hydrodynamical properties of rocking SUBs not yet well systematized. The aim of the study was to determine a quantitative characteristic of mixing time in a ReadyToProcess WAVE 25 system equipped with a 2-litre Cellbag disposable container, with the use of a sensor method and the Design of Experiment (DoE) methodology. The DoE-based approach has been used to screen significant operational parameters and evaluate their impact on the values of mixing time reached in the studied rocking SUB system. To quantify relations between operational parameters and important process quantities in rocking disposable bag-like containers of different sizes, a set of original formulas for generalization of experimental data and predicting mixing time values has been proposed. The set includes exponential correlations and a correlation involving a dimensionless filling level term and a modified Reynolds number expression. Comparisons between estimations and experimental data have shown satisfactory levels of accuracy within ± 30% of experimental values. The correlation involving dimensionless terms can be applied for disposable bag-like containers offered by different manufacturers and of various sizes.