Viscous fingering in size exclusion chromatography: Insights from numerical simulation

A two-dimensional hybrid finite difference/particle-tracking simulation has been used to study the now nonuniformities induced by the viscous fingering instability during size exclusion chromatography of proteins. The numerical simulation faithfully reproduces the morphology and dynamics of viscous fingering observed in magnetic resonance images of sample migration through operating chromatography columns. In addition to sample intrinsic viscosity, solute molecular diffusivity and packing heterogeneities are found to have a significant impact on finger dynamics. More so than in chromatography of solutes which do not enhance viscosity, packing heterogeneities lead to considerable increases in HETP for viscous samples. Where intraparticle mass transfer resistances are small, the effect of fingering on HETP is almost independent of velocity.