Comparing 3- and Sub-2 µm Particle Performance in High-Throughput Chiral Screening with Supercritical Fluid Chromatography

The performance benefits of small particles in packed column chromatography are well documented. These known benefits, combined with the advantages of supercritical fluid chromatography (SFC), suggest the possibility for fast, high-throughput chiral screening, which can dramatically reduce the time spent on method development. In this work, we rationalize column dimension selection for high-throughput SFC chiral screening in light of modern instrument capabilities and factors like extra-column volume variance and maximum operating pressures. Columns packed with 3- and sub-2 µm particles are compared with respect to kinetic performance, resolving power, and the practical limitations imposed by high-pressure operation.