Preparative packed-bed chromatography for purification of macromolecular bioproducts is often operated at its hydrodynamic limit leading to a complex, hysteretic, thus, history-dependent packed bed behavior. The theoretical understanding of the causes is still limited. A novel rigorous modeling approach of the chromatography column on the particle scale has been made which takes into account the interparticle micromechanics and fluid-particle interactions for the first time. A three-dimensional deterministic model was created by applying Computational Fluid Dynamics (CFD) coupled with the Discrete Element Method (DEM). Different column packing strategies and the packing long-term behavior during simulated cyclic load/elution operation were investigated in-silico as well as in laboratory experiments. The simulation reproduced the measured data with great accuracy regarding the packing compression behavior and the pressure-flow dependency. The individual study of flow and mechanical compression revealed distinct differences in the dynamic packing behavior which were related to the packing strategy as well as to medium wall support. During flow compression, the packed-bed exhibited a pronounced axial packing density gradient leading to the most compressed region at the column outlet. In contrast, mechanical compression led to an exponential packing density profile with the most compressed region at the column entrance. During compression, still existing void spaces in the packed bed being surrounded by a force chain network were detected by UV-microscopy. Simulation results indicate that this packing anisotropy is governed by particle-wall and interparticle friction effects with significant influence on the axial and radial fluid flow distribution. Improved packing quality in terms of the homogeneity and long-term stability was achieved for the first time by a modeling-based systematic combination of flow packing and dynamic axial compression.

Modeling of axial and radial heterogeneity of preparative chromatography packings

253rd National Meeting (2017)

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