On the intrinsic effect of the particle size distribution on the permeability of particulate liquid chromatography columns. A theoretical overview.

This study presents a theoretical investigation into the intrinsic influence of particle size distribution (PSD) on the permeability of packed beds in liquid chromatography columns. Using a log-normal PSD derived from experimental data on 2μm BEH 66Å Particles, the work explores how different definitions of average particle size, number-, volume-, and surface-area-weighted (Sauter mean), affect the comparison between monodisperse and polydisperse particle packings when estimating the solid-to-fluid surface area in various models of column permeability. By normalizing permeability to a constant void fraction and average particle size, it is shown that the calculation of the permeability of columns packed with polydisperse particles is found to be either higher or lower than that of monodisperse packings, depending on the chosen reference particle size. Notably, for the same void fraction and Sauter mean diameter, the width of the particle size distribution (PSD) of any chromatographic packing material has no intrinsic impact on the column permeability. This confirms that, in addition to void fraction, the Sauter mean diameter or the specific surface area is the second most critical parameter for fair and meaningful comparison. These findings are supported by analytical derivations and validated against published fluid dynamics simulations across a broad range of microstructures composed of both highly polydisperse and strictly monodisperse non-overlapping sphere packings as well as few simulated and measured permeability data of liquid chromatography columns. Overall, the results offer a robust framework for interpreting column permeability and guiding particle design strategies aimed at maximizing chromatographic speed and performance.