(313a) Characterizing the Performance of a Rocking Bioreactor for Efficient Mixing and Oxygen Transfer Using a Novel Computational Framework

Bioreactors are essential for the production of various biological products using cell culturing, such as vaccines, bioplastics, pharmaceuticals, and cultivated meat. In the context of producing cultivated meat, rocking or wave-mixed bioreactors have emerged as a promising innovation due to their disposable nature, low operating expenses, and scalability. However, despite these advantages, the performance of the rocking bioreactor is not well characterized in view of its short history in the market, and the wide range of geometrical and operating parameters.

In the present study we quantitatively evaluate mixing, oxygen transfer, and shear stress within a rectangular rocking bioreactor with different operating conditions based on an implementation in the Basilisk open-source platform. We use the second-order finite volume Navier-Stokes solver and a volume-of-fluid interface reconstruction scheme to accurately resolve the highly nonlinear fluid motion. The non-inertial reference frame fixed into the rocking geometry is used for the formulation of the Navier-Stokes equation, which leads to the addition of non-inertial acceleration terms in the momentum balance equation. By solving the advection-diffusion equation for soluble tracers and oxygen transfer in the multi-fluid system, we examine the degree of mixing and oxygen transfer coefficient (kLa).

For the simulation the rectangular geometry is defined with an aspect ratio of 3.5 that represents a Cell-tainer 2L bag. The bioreactor is operated with a sinusoidal periodic motion, and the operating conditions range from 3 degrees and 10 rpm to 7 degrees and 37.5 rpm for the rocking degree and frequency, respectively. To avoid violent rotating motion at the start and mimic practical motions in experiments, we weakly accelerate the bioreactor with small amplitudes until it reaches the regular amplitude. The tracers and oxygens are released after the bioreactor reaches the periodic state.

Specifically, we highlight two critical hydrodynamic phenomena that affect the performance of the bioreactor. Firstly, we investigate the transitional regime from laminar to turbulent flow, generally unpreferable for cultivated meat production. Moreover, we identify certain operating conditions within the laminar flow regime, which significantly enhance mixing and oxygen transfer. Our findings are expected to provide valuable guidelines for designing optimized bioreactors for the next generation of cultivated meat industry pipelines.