Does Particle Size Distribution Matter in Speed and Resolution of Liquid Chromatography Columns?

The fundamental relationship between the performance of liquid chromatographic columns, particularly separation speed and resolution, and the macrostructure of randomly packed beds of spherical particles has been a central theme in chromatography research since the 1960s (Horvath, Giddings, Knox). Achieving both faster and higher-resolution separations has driven innovations towards elevated operating temperatures, more ordered bed structures (Regnier, pillar array columns), reduced flow resistance via highly porous monoliths (Tanaka, Svec), and the transition from HPLC (400 bar) to UHPLC (1000–1500 bar) using sub-2 µm particles at very high pressures (Jorgenson, Waters Corporation 2004).

Despite continued advancements in column technologies, such as sub-3 µm core-shell particles with narrow particle size distributions (PSDs) (Kirkland, Advanced Material Technologies, 2007) and the development of quasi-monodisperse particles, the precise impact of PSD on the speed–resolution characteristics of modern liquid chromatography columns remains unresolved. It continues to spark active scientific debate, often driven more by opinion and unverified assumptions than by validated evidence.

In this presentation, we revisit key simulation and experimental studies to examine the intrinsic role of PSD in determining column permeability and efficiency. We will also highlight the critical physico-chemical parameters that should be considered to achieve the ultimate performance of randomly packed LC columns packed with spheroidal particles.