Serially coupled column liquid chromatography: An alternative separation tool

Despite the rapid development of liquid chromatography (LC) in recent decades, it remains a challenge to achieve the desired chromatographic separation of complex matrices using a single column. Multi-column LC techniques, particularly serially coupled column LC (SCC-LC), have emerged as a promising solution to overcome this challenge. While more attention has been focused on heart-cutting or comprehensive two-dimensional LC, reviews specifically focusing on SCC-LC, which offers advantages in terms of precision and facile instrumentation, are scarce. Here, our concerns are devoted to the progress summary regarding the instrumentation and applications of SCC-LC. Emphasis is placed on column selection aiming to enlarge peak capacity, selectivity, or both through the optimization of combination types (e.g. RPLC-RPLC, -RPLC-HILIC, and achiral-chiral LC), connection devices (e.g. zero dead volume connector, tubing, and T-type connector), elution program (i.e. isocratic or gradient) and detectors (e.g. mass spectrometer, ultraviolet detector, and fluorescence detector). The application of SCC-LC in pharmaceutical, biological, environmental, and food fields is also reviewed, and future perspectives and potential directions for SCC-LC are discussed. We envision that the review can give meaningful information to analytical scientists when facing heavy chromatographic separation tasks for complicated matrices.