A Detailed Investigation of Mass Transfer Phenomena in Core-shell Particles with Different Particle and Pore Sizes

Since their re-introduction in 2006, columns packed with core-shell particles have revolutionized liquid chromatography separations [1]. These particles, also known as fused-core or superficially porous particles, are commercially available in column lengths as short as 3 cm, particle sizes smaller than 2 μm and pore sizes ranging from 90Å to 1000Å [1–3]. These columns have shown superior performance in terms of reduced plate height, lower backpressure, and increased analysis speed [1,3,4].

Core-shell particles are employed to analyze compounds of any size, from small
molecules to DNA fragments, monoclonal antibodies, large proteins, and polystyrene standards. In general, for small molecules, pore sizes of 90-100Å are employed. Columns with larger pore sizes are required to analyze large (bio-) molecules, as the pores should be sufficiently large to allow molecules to diffuse inside the pores freely.

This study aims to provide a detailed investigation of mass transfer mechanisms in RPLC columns with core-shell particles for representative small and large (bio-) molecules. This is obtained by a detailed assessment of the individual contributions to their mass transfer for a set of 6 columns, with pore sizes between 90 and 1000 Å, particle sizes of 2.7 μm and 3.4 μm, and different stationary phase ligands (C4 and C18). For this purpose, plate heights are measured on the columns of interest over a range of different flow rates. The
individual contributions to mass transfer are determined next and should, summed together, result in the overall determined plate heights. Peak parking experiments are performed to determine the effective diffusion coefficient (Deff). Knowledge of Deff allows to accurately extract the intra-particle diffusion coefficient (Dpart) [5]. The observed differences in intra-particle diffusion are then related to differences in pore size, porosity and stationary phase functionality.