Fluid dynamics and mixing behavior in orbitally shaken bioreactors for mammalian cell cultivation

Rationale and significance. Recombinant therapeutic proteins are frequently produced in mammalian cells cultivated in suspension in large-scale stirred tank bioreactors. There are three major drawbacks to stirred-tank bioreactors. First, they are expensive to purchase and maintain, limiting their availability to some potential users. Second, they have not been adapted to volumetric scales less than a liter, making studies at small-scale difficult to extrapolate to large-scale. Third, non-homogeneous mixing and limited mass transfer capacity are frequently observed in these bioreactors since mild agitation must be employed to prevent shear stress to cells. As an alternative, the LBTC has begun to develop orbitally shaken bioreactors for suspension cultivation of mammalian cells at scales of operation from a few mLs to 1,000 L. Orbital shaking is scalable and it confers less shear stress on cells than observed in stirred-tank vessels [13, 74].