Despite progress in hardware and column technology, the complexity and heterogeneity of many samples still pose a challenge for state-of-the-art 1D liquid chromatography (LC). As an effective answer to these analytical questions, multidimensional comprehensive techniques have become an attractive strategy across disciplines. This Primer provides a general overview of 2D comprehensive LC (LC × LC), including hardware, software and best practices for experimentation. The underlying principles are described, alongside the requirements of separation and detection equipment. In addition, this Primer discusses data collection, processing and analysis, with an exploration of inherent challenges and possible workarounds. Selected examples are presented to show how the gain in resolution afforded by LC × LC has enabled in-depth characterization of complex non-volatile samples, such as pharmaceuticals, polymers, foods and the ‘omics. Finally, the technique progress is evaluated, with an outline of future directions for the field.

尽管硬件和色谱柱技术取得了进步，但许多样品的复杂性和异质性仍然对最先进的一维液相色谱 (LC) 构成挑战。作为这些分析问题的有效答案，多维综合技术已成为跨学科的有吸引力的策略。本入门手册提供了 2D 综合 LC (LC × LC) 的总体概述，包括硬件、软件和实验最佳实践。描述了基本原理以及分离和检测设备的要求。此外，本入门手册还讨论了数据收集、处理和分析，并探讨了固有的挑战和可能的解决方法。选定的示例展示了 LC × LC 所提供的分辨率增益如何能够对复杂的非挥发性样品（例如药物、聚合物、食品和组学）进行深入表征。最后，评估了技术进展，并概述了该领域的未来方向。