The role of particle size distribution on permeability and efficiency of slurry-packed liquid chromatography columns

This review critically examines past and recent studies addressing the intrinsic role of particle size distribution (PSD) in high-performance liquid chromatography (HPLC), with a focus on speed and efficiency. The discussion integrates theoretical models of bed permeability and plate height with experimental evidence to assess the influence of PSD on column permeability and chromatographic resolution. Overall, most findings indicate that PSD has little or no intrinsic impact on key performance metrics, including column permeability, longitudinal diffusion, short-range axial dispersion, and solid-liquid mass transfer, when comparing randomly packed beds of monodisperse and polydisperse particles under equivalent conditions of bed porosity and mean diameters: the Sauter mean diameter for permeability and eddy dispersion and the squared volume-weighted mean particle diameter for slow intraparticle diffusion and high speeds. Rather than reducing particle size polydispersity, efforts should prioritize improved packing methodologies and particle morphologies to minimize long-range structural heterogeneities across the column diameter. While random sphere packings remain the current standard, monodisperse particles may offer some potential for next-generation column technology by enabling highly ordered particulate systems known to deliver superior resolution.