Local fluid dynamic stress in stirred tank bioreactors along Lagrangian trajectories

Abstract

High-density cultivation of mammalian cells in stirred tank bioreactors requires balancing oxygen transfer with minimizing fluid dynamic stress that damages sensitive cells. This study investigates energy dissipation rates (EDR) from a Lagrangian perspective to understand fluid mechanical stresses experienced by individual cells. Using Lattice-Boltzmann Large Eddy Simulation, we modeled a 30 L stirred tank reactor with dual impellers (Rushton turbine and pitch blade) at 270 rpm. Cell trajectories were simulated using 10,000 particles representing Chinese hamster ovary (CHO) cells. The critical EDR threshold was defined as producing a Kolmogorov length scale equal to cell diameter. Results reveal significant discrepancies between time-averaged literature data and transient simulation results. Lagrangian tracking shows cells experience brief but intense exposure to high EDR regions, with EDR peaks significantly exceeding established maximum values (𝜀T,max 𝜀̅T⁄ ≈ 40). This indicates conventional steady-state analyses underestimate actual fluid stress experienced by cells. This Lagrangian approach suggests cell damage mechanisms are better understood through statistical analysis of peak stress magnitude, exposure duration, and frequency rather than time-averaged values, with important implications for optimizing bioreactor design.