Electrospray ionization in concentrated acetonitrile vapor improves the performance of mass spectrometry for proteomic analyses

Suppressing the background interferences and enhancing the analytes signals are long-term goals in high performance electrospray ionization mass spectrometry (ESI–MS) analyses. We observed that performing electrospray in the presence of a concentrated acetonitrile atmosphere suppresses background interferences and enhances peptide signals. An enclosed nanoESI source was utilized to provide a stable atmosphere of concentrated acetonitrile vapor for high performance ESI–MS analyses. The median MS signal intensity increased by 5 times for a set of 23 BSA tryptic peptides in direct ESI–MS analysis. Further, the number of reproducibly and precisely quantified peptides could be improved 67% in six replicate label-free quantitative proteome analyses by this strategy.