Simulation-based Design of Bioreactors Using Computational Multiphysics

Abstract

The Covid-19 pandemic highlighted the importance of quickly scaling up the production of vaccines and other pharmaceutical products. These products are typically made within bioreactors: vessels that carry out bioreactions involving microorganisms or biochemical substances derived from microorganisms. The design, construction, and evaluation of bioreactors for large-scale production, however, is costly and time-consuming. Many builds are often needed to resolve issues such as poor mixing and inhomogeneous nutrient transfer. Nevertheless, computational methods can be used to identify and resolve these limitations early-on in the design process. This is why understanding the flow characteristics inside a bioreactor through computational fluid dynamics (CFD) can save time, money, and lives.

Bioreactors contain three phases: 1) a continuous liquid medium which is the host for cells to feed and grow, 2) a dispersed solid phase which is the microorganism particles inside the tank, and 3) a dispersed gas phase which includes the air or oxygen bubbles for microorganisms aspiration. Due to the complexity of solving a three-phase flow problem, most bioreactor multi-phase simulations in the literature neglect the dispersed microorganism phase and its effects entirely–thus assuming two phases only.

In this research project, a hybrid model is developed that captures the effects of all three phases. The model first approximates the liquid and solid phase as a single “mixture” using the drift-flux model. Subsequently, the Euler-Euler method is used to simulate the resulting mixture with the added dispersed gas. This allows the simulation of bioreactors and other bioprocesses with the computational complexity of the two-phase simulation while capturing all three phases.

The “mixture” portion of the model was simulated inside a stirred tank bioreactor. Its results were then validated by comparing them to empirical evidence in the literature. Two parameters were chosen for this validation: 1) the hindered settling velocity of the solid phase in the absence of impeller motion, and 2) the computed power number of the impeller. The validation showed an overestimation of the hindered settling velocity and an underestimation of the impeller power number.