P24: Mixing and flow dynamics in a cylindrical shaken bioreactor

Shaken microwell plate formats are largely employed in the early stages of bioprocess development because they offer a low power consumption solution to screen several processes in parallel (Lye et al, 2003).  These bioreactors have recently become available in larger pilot and industrial scale in the form of single-use cylindrical bags on a controllable shaken platform.

The current work provides a thorough characterization of the flow and mixing dynamics occurring in a cylindrical shaken bioreactor for different operating parameters: medium height H, bioreactor diameter, D, orbital shaken diameter, d, Reynolds number, Re and Froude number, Fr. Phase resolved velocity and mixing time measurements were obtained by Particle Image Velocimetry (PIV) and a pH-decolourisation technique, respectively, to better comprehend how local flow characteristics affect the mixing performance of the bioreactor. The results obtained highlight a significant flow transition with a toroid vortical structure being present for Fr<(0.5 H/D)^0.5, while a vertical precessional vortex occurs for Fr>(0.5 H/D)^0.5. This second condition has been denoted in the literature as the “out of phase phenomenon” and has been mainly associated to a phase delay of the free surface oscillation. Mixing time measurements confirm the findings of the flow analysis, with a diffusion zone being present towards the bottom of the bioreactor when operating conditions are selected such that the toroid vortex does not extend through the entire medium height. These results provide essential insight into the design of shaken bioreactors and process conditions, and offer valuable information for the selection of scale-up methodologies.