A CFD-based model for predicting shear-induced DNA breakage in mix tanks

摘要

A new approach to modeling the degradation kinetics of large biological macromolecules (i.e. DNA) in a mixing tank is proposed which utilizes Computation Fluid Dynamic Modeling (CFD). The approach is based on the premise that molecules break only when they pass through a small region of high shear near the impeller. The CFD simulations can be used to estimate the size of this "high-shear" zone for a given impeller (i.e. RPM, DIT, off-bottom distance). The breakage of 35 kilobase (IB) fragments of DNA from salmon sperm was monitored using gel electrophoresis, and found to increase with the agitation rate of a standard Rushton turbine. The experimental data indicates that the CFD models, employing a RNG turbulence model and a dense numerical grid around the impeller, predict reasonably well the size of the "high-shear" zone in mixing tanks. This modeling and experimental approach can be used to assist in the scaleup of batch bioprocesses, where the shear-induced degradation of the bio-product is a concern.