Raena Morley, Mirjana Minceva

Liquid–Liquid Chromatography: Current Design Approaches and Future Pathways

Annual Review of Chemical and Biomolecular Engineering https://doi.org/10.1146/annurev-chembioeng-101420-033548

Abstract

Since its first appearance in the 1960s, solid support–free liquid–liquid chromatography has played an ever-growing role in the field of natural products research. The use of the two phases of a liquid biphasic system, the mobile and stationary phases, renders the technique highly versatile and adaptable to a wide spectrum of target molecules, from hydrophobic to highly polar small molecules to proteins. Generally considered a niche technique used only for small-scale preparative separations, liquid–liquid chromatography currently lags far behind conventional liquid–solid chromatography and liquid–liquid extraction in process modeling and industrial acceptance. This review aims to expose a broader audience to this high-potential separation technique by presenting the wide variety of available operating modes and solvent systems as well as structured, model-based design approaches. Topics currently offering opportunities for further investigation are also addressed.