(33a) Synchronized Mixing, Bubble Size Distribution, and KLa High-Fidelity Simulation for Optimization, and Scale-up for Benchtop Biofilm Bioreactor
AIChE Annual Meeting
2022
2022 Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Predictive Scale-Up/Scale-Down for Production of Pharmaceuticals and Biopharmaceuticals I
Sunday, November 13, 2022 - 3:30pm to 3:52pm
The overall mixing performance, shear rate impact on cellsâ behavior, distribution, and population balance of gas bubbles, are characteristic indication of the system at steady-state. However, the mass transfer, kLa, oxygen consumption and carbon dioxide release, cell growth, and biofilm characteristics are transient and scale dependent. On the equipment consideration side, the heat transfer area, sparger design and aeriation rate (i.e., bubble size), volume to height ratio, radial/axial dispersion of fluid flow and energy distribution are other nonlinearities in the systems. Studying these aspects individually cannot provide a holistic view on the bioreactor performance, and any tools and knowledge developed this way is incomplete and cannot be used for robust process development, optimization, and efficient scale-up.
In this study, we developed and adopted a synchronized mixing, bubble size distribution, and kLa high-fidelity simulation (computational fluid dynamic-CFD) for a customized biofilm bioreactor. All physics and system nonlinearities were considered at different scales. Transient two-phase flow simulations were conducted were a S-Gamma population balance was included to consider the breakup and coalescence of gas bubbles.
The model also includes the interaction of the gas bubbles with the mixing element of the bioreactor, and its effect on the mass transfer and kLa. Furthermore, a unique impeller design was customized and optimized for a biofilm bioreactor. Different design characteristics of the impeller (e.g., length, number of elements, etc.), and bioreactor operating conditions, such as RPM, were evaluated in the performance of the mixing properties (i.e., pumping and mixing number) and mass transfer characteristics (i.e., kLa, distribution of the oxygen/carbon dioxide in the biorector, and gas bubble size distribution).