Hydrodynamics and mass transfer in spinner flasks: Implications for large scale cultured meat production.

• The hydrodynamics characteristics of spinner flasks cannot be reproduced at scale. • Stirred tank reactors are unsuitable for microcarrier based cultured meat at scale. • Sparging causes more hydrodynamic stress than agitation in stirred tank reactors. • Stirring at >120 rpm in a 250 mL spinner flask is needed to mimic scaling-up effects. Cultured meat has emerged as a potential alternative source of animal proteins and fat. Commercially viable cultured meat production likely requires proliferation bioreactors much larger than those used in the pharmaceutical industry today. However, most lab-scale process developments are carried out in spinner flasks that cannot be readily scaled-up using conventional, semi-empirical methods. We systematically investigated the hydrodynamics and mass transfer characteristics of a 250 mL spinner flask under 30−120 rpm stirring speeds and 50 or 100 mL filling volumes, as well as 0−30 g/L microcarriers, to facilitate scale-down experiment design hence the transfer of lab-generated knowledge to large scale bioreactors. It was found that meat cells are typically cultured under operating conditions that give a combination of <10 s mixing time and about 1 mW/kg energy dissipation rate, but with high dissolved oxygen concentrations. Computational fluid dynamics moelling was performed for both the spinner flask and a generic cell culture reactor of 20 m³ working volume. Simulations suggested that it might not be possible to reproduce the most favourable conditions in large scale reactors. In particular, even when operated at a stirring speed close to the N js , the shear exerted by the impellers alone could cause cell detachment from microcarriers, while even more hydrodynamic stress is introduced via sparging. [ABSTRACT FROM AUTHOR]