The interface between the two separation dimensions is a key element of any comprehensive two‑dimensional liquid chromatography (LC×LC) system. LC×LC has typically been implemented by using one or more switching valves, equipped with either sampling loops or trap column(s). Temperature manipulation is a relatively unexplored yet promising route towards non-valve-based LC×LC. The fairly recent emergence of thermal modulation has provided a less conventional method for performing LC×LC separations. This article illustrates the variety of commonly used modulators, paying specific attention to focusing modulators.
Stacking and sweeping injection methods are compared and practical suggestions are provided about how to enhance sensitivity for charged and neutral compounds.