Influence of different packing methods on the hydrodynamic stability of chromatography columns.

It is well known that packing non-uniformity may cause peak asymmetry and limit the performance of packed-bed chromatographic columns. However, understanding of the reasons leading to packing non-uniformity is still limited. Therefore, the effect of different column packing methods, i.e. dynamic axial compression (DAC), flow packing, and combinations of both on the hydrodynamic packing heterogeneity and stability of packings composed of polymer-based compressible porous resins with a mean diameter of 90μm was investigated experimentally as well as in-silico. Deterministic Euler-Lagrange modeling of a small chromatographic column with a diameter of 9.6mm and a bed height of 30mm was applied by coupling Computational Fluid Dynamics (CFD) and the Discrete Element Method (DEM). Interparticle micromechanics as well as the fluid-particle and particle-wall interactions were taken into account. Experiments and simulations revealed substantial non-uniformity of compression force transmission and axial packing density distribution during both dynamic axial compression and flow packing which was related to wall support and interparticle friction. By combining both packing methods sequentially (dynamic axial compression followed by flow packing or vice versa), the compression forces were more homogeneous resulting in improved packing procedures. Repeated alternating application of flow packing and DAC (the so-called hybrid packing method) resulted in the most homogeneous packing density distribution and the highest packing stability which was kept nearly constant during long-term operation with cyclic hydrodynamic load. The hydrodynamic stability of the chromatographic column was evaluated by calculating the integral porosity deviation and packing induced flow velocity dispersion. The hybrid packing method gave the best results for both parameters.