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Large Eddy Simulation of Industrial-Scale Agitated Bioreactors:
Mechanistic Analysis of Impact of Sparger Design on Cell Damage and
Interphase Mass Transfer
Abstract
The intricate dynamics of local liquid-gas interactions in agitated
bioreactors poses a difficulty in understanding the mechanistic
relationships among critical operational design parameters and cellular
growth, especially for large-scale pharmaceutical production.
Traditional computer models have advanced the understanding of such
complex interactions. Their implementation is, however, associated with
considerable computational costs, power and wall-clock time, to
effectively simulate dynamic multiphase phenomena existing within
bioreactors. This study explores a novel modeling approach that
leverages high-resolution Large Eddy Simulation (LES) and the Lattice
Boltzmann Method (LBM) to simulate turbulent flows within an industrial
bioreactor. This approach allows the practical simulation of millions of
bubbles modeled individually in a computationally accelerated manner.
The model performance was evaluated with the experimental data obtained
at various working volumes, aeration and agitation conditions. A further
comparison with a conventional Reynolds-averaged Navier–Stokes method
also provided comparable results. Furthermore, to complement the
root-cause analysis conducted experimentally, a detailed model was
developed to comprehend the underlying mechanisms for cell death,
incorporating changes in individual bubble sizes due to various mass
exchanges, fluid-gas forces and hydrodynamic pressure. Additionally, the
model provided in-depth insights into other technical considerations for
a proposed change in the sparger design at elevated gassing flow rates,
including oxygen transfer rate, bubble breakup rate and impeller
flooding transitions.