Mixing and oxygen transfer characteristics of a microplate bioreactor with surface-attached microposts.

ABSTRACT

Bioprocess optimization for cell-based therapies is a resource heavy activity. To reduce the associated cost and time, process development may be carried out in small volume systems, with the caveat that such systems be predictive for process scale-up. The transport of oxygen from the gas phase into the culture medium, characterized using the volumetric mass transfer coefficient, kL a, has been identified as a critical parameter for predictive process scale-up. Here, we describe the development of a 96-well microplate with integrated Redbud Posts to provide mixing and enhanced kL a. Mixing in the microplate is characterized by observation of dyes and analyzed using the relative mixing index (RMI). The kL a is measured via dynamic gassing out method. Actuating Redbud Posts are shown to increase rate of planar homogeneity (2 min) verse diffusion alone (120 min) and increase oxygenation, with increasing stirrer speed (3500-9000 rpm) and decreasing fill volume (150-350 µL) leading to an increase in kL a (4-88 h-1 ). Significant increase in Chinese Hamster Ovary growth in Redbud Labs vessel (580,000 cells mL-1 ) versus the control (420,000 cells mL-1 ); t(12.814) = 8.3678, p ≤ .001), and CD4+ Naïve cell growth in the microbioreactor indicates the potential for this technology in early stage bioprocess development and optimization.