Multiphase Fluid Mechanics in Biomanufacturing

The aim of this fluid mechanics work was to study the fundamental hydrodynamics mechanism in a balloon type bubble bioreactor (BTBB), which could provide a key guidance to improve biomanufacturing of biopharmaceuticals. A multiphase (liquid and air) computational fluid dynamics was performed with particle tracking velocimetry to observe flow patterns inside BTBB. The control experiment was investigated in 5 and 20L BTBB with water observed an increase in the bubble diameter (0.15 to 0.24 cm for 2L working volume in 5L; 0.27 to 0.36 cm for 16L working volume in 20L) with increasing volumetric flow rate (1 cc/min to 5.5 cc/min) and working volume (2L, 4L, 8L and 16L). However, the bubble diameter reduced with increasing interface forces such as viscosity, density and surface tension when compared with water (0.14 cm at 5.5 cc/min in salt solution; while it was 0.24 cm in water). The decrease in density and viscous fluid could be due to low detachment time and increasing density of the bubble or prevention of bubble coalescence. The reduction in surface tension (30 dynes/cm) resulted in the activation of sparger pores leading to the formation of numerous small bubbles. A homogeneous or laminar flow was observed in higher flow rates (3 cc/min) with increasing viscosity (5 mPa.s) and the flow was turbulent or heterogeneous with flow rates higher than 3 cc/min (4, 5, 5.5 cc/min). Moreover, the dual effect of increasing viscosity and density decreased the bubble sizes in case of CO2 and had laminar flow for higher flow rates (3 cc/min) when compared with the individual effect of density and viscosity. The flow data shows that the differential fluid mechanics pattern in non-uniform geometry BTBB, which can be used to design a flow sensor that could accurately controlling the mixing rate or mass transfer in large-scale biomanufacturing.