Nanoflow liquid chromatography/mass spectrometry (nano-LC/MS), which has been developed from 1990s, generates increasing interest because it offers high detection sensitivity, reduces sample consumption and analysis time.In order to get a more stable and robust nano-LC/MS platform, a new generation of HPLC-Chip/MS system has been developed.All functional components, including enrichment column, analytical separation column and nano-electrospray emitter, were integrated onto this microfluidic device, which can significantly reduce the possibility of leaks and dead volumes, and greatly improve the ease of use during analysis.This miniaturized analytical platform results in less sample consumption, dilution and improved overall analyte ionization efficiency, and ultimately leads to the pronounced sensitivity advantage compared to conventional LC/MS.At present, most of the applications of new HPLC-Chip/MS system have been focused on proteomic analysis.However, the high sensitivity, ease of use and reusable nature of this device makes it attractive for small molecule analysis.