High-Definition Simulation of Packed-Bed Liquid Chromatography in Laterally Unconfined Compartments

  • Xu, Xiang (RWTH Aachen University)
  • von Lieres, Eric (Forschungszentrum Jülich)
  • Behr, Marek (RWTH Aachen University)

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Packed-bed liquid chromatography is widely utilized in biotechnology and other industries as a critical unit operation in downstream processing, i.e., the separation and purification of valuable molecules from unwanted side products and other substances. While reduced-order models enable efficient simulations, they rely on extensive experimental calibration and do not provide mechanistic insights into how specific morphological features influence local hydrodynamics and separation performance. These features include particle size distribution, particle geometry, local packing irregularities, and wall effects. High-definition modeling addresses these limitations by resolving full spatial details, yet previous studies have been restricted to confined cylindrical geometries with very narrow columns. These constraints introduce substantial wall effects that alter local flow behavior and limit applicability to larger-scale systems. In this work, we have extended high-definition chromatography simulation from laterally confined to unconfined compartments by establishing a validated workflow encompassing periodic packing generation, meshing, partitioning, CFD simulation and post-processing. The chromatography problem is simulated using the highly parallel multi-physics solver XNS with a stabilized space-time finite element method on the JURECA supercomputer at Forschungszentrum Jülich. The steady-state incompressible Navier-Stokes equations are first solved to obtain the interstitial flow field, followed by multi-domain transport modeled via the advection-diffusion equation in the interstitial region and the diffusion-reaction equation within porous particles, with binding behavior described by the Langmuir isotherm. This workflow allows to simulate packings with up to 10,000 particles in unconfined compartments, facilitating the investigation of local hydrodynamics without wall effects in industrial-scale applications. The resulting intra-column data is used to calibrate axial dispersion and film diffusion parameters in the corresponding reduced-order model within CADET. The impact of particle size distribution and wall effects on these parameters will be discussed in the presentation.