Maximizing the speed of separations for industrial problems

Recent improvement efforts in chromatography have provided great improvements in the rate of plate production, but less attention has been spent on optimizing the kinds of problems that are most often encountered in industry. When factors are not independent in their effects on the responses of a chromatographic separation, all adjustable factors must be considered in concert in seeking the best or optimum condition that solves the problem. This requires careful attention to specifying the goals, the adjustable factors, and the constraints required to make sure the outcome can actually be implemented. Strategies for optimizing assay and screening methods in the context of industrial needs are presented. Expanding the factor space of the system being investigated can lead to better outcomes. The prospect of adding column-outlet pressure control and expanding the mobile phase composition to include condensed gases or supercritical fluids is explored. Reversed-phase liquid chromatography, hydrophilic interaction chromatography, electrostatic repulsion hydrophilic interaction chromatography, and supercritical fluid chromatography are contiguous with regard to mobile phase characteristics. Adjustment of selectivity through instrument-controlled factors can benefit method development. Opportunities obtained by blending modifiers, varying temperature and pressure with compressible mobile phases, and controlling pH are discussed in the context of optimizing methods.

► Goal setting depends on the separation needs and the capabilities of the system.
► A multi-dimensional space describes the adjustable factors.
► Expanding the factor space adds potential improvement.
► Several means of adjusting selectivity without system changes are reviewed.
► We summarize a method development approach utilizing modeling and optimization.