Comparison of Perfusion Culture Performance in Orbitally Shaken Bioreactors and Stirred Tank Bioreactors: A Spatiotemporal Dynamic Analysis of Shear Stress and Mass Transfer Based on Suspension Rheology

This study examines the differences in performance between orbitally shaken bioreactors (OSBs) and stirred tank bioreactors (STBs) in Chinese Hamster Ovary (CHO) cell perfusion culture in response to the growing market demand for monoclonal antibodies (mAbs). Although OSBs demonstrated higher cell densities, a notable reduction in specific antibody production rates was observed during the mid-to-late phases of the culture compared with STBs. To elucidate the underlying mechanisms, the rheological behaviour of high-density cell suspensions in both reactor types was initially characterised, confirming their adherence to the Sisko fluid model. Computational Fluid Dynamics (CFD) analysis revealed the influence of these rheological properties on the shear stress distribution and mass transfer. This analysis identified the key limiting factors for achieving higher cell densities: mass transfer efficiency in OSBs and shear stress in STBs. Using an Euler–Lagrangian cell-tracking methodology to analyse cellular “lifelines”, it was determined that OSBs exhibited approximately twice the number and frequency of shear stress peak occurrences compared to STBs. This persistent mechanical stimulation likely contributes to the reduced specific antibody production rates observed. This comprehensive investigation not only clarifies the comparative advantages and limitations of different bioreactor types in perfusion culture but also provides a robust theoretical basis and technical guidance for informed reactor selection, optimisation, and scale-up in industrial production environments.