What still hinders the routine application of miniaturized liquid chromatography beyond the omics sciences?

Miniaturized LC, encompassing capillary and nanoLC, presents significant analytical advantages in enhanced chromatographic performance and detectability and delivers considerable environmental and economic benefits. Despite these advantages, its utilization has primarily remained confined to omics sciences, with limited adoption in the routine targeted analysis of small molecules despite the lack of practical limitations. Initially, miniaturized LC encountered challenges related to scale reduction, necessitating the handling of minute sample volumes and lower flow rates. However, these obstacles have largely been overcome, with various instrumental platforms, columns, and consumables now available for efficient separations at the miniaturized scale. Moreover, the miniaturization of instruments facilitated by capillary and nanoLC has given rise to various portable LC platforms for in-situ analysis in recent years. Currently, researchers are exploring their applicability for diverse analytical purposes. However, the transition from conventional HPLC to miniaturized LC has been slow, and the technical factors limiting this shift still need to be clarified. Limited access to technology is among the primary obstacles identified, as transitioning may entail replacing conventional instruments with miniaturized versions.

Additionally, a lack of proper training and background to handle small volumes and flow rates has hindered the widespread adoption of capillary and nano-LC. Notably, expertise in HPLC only sometimes translates to proficiency at the miniaturized scale. Through this review, we aim to facilitate the dissemination of miniaturized LC by providing readers with a comprehensive overview of its current state, showcasing recent advancements, and highlighting remarkable applications beyond omics sciences.