In theory, the analyte sensitivity increases on decreasing the column inner diameter; however, because of the very low sample volumes injected – 20-60 nL, nano liquid chromatography cannot be considered as an analytical method of high sensitivity.

There are several research studies that focused on the improvement of sensitivity by using techniques such as on-column focusing[1] and 2-D separation[2].

1. “Trace Level Determination of Organophosphorus Pesticides in Water with the New Direct-Electron Ionization LC/MS Interface”, Achille Cappiello et al., Analytical Chemistry, 2002 vol. 74 pp. 3547-54

2. “Fully automated micro- and nanoscale one- or two-dimensional high-performance liquid chromatography system for liquid chromatography-mass spectrometry compatible with non-volatile salts for ion exchange chromatography” by Masuda, J. et al., Journal of Chromatography A 2005, 1063, pp. 57-69.