ABSTRACT
A previous comparative study between helium and nitrogen as nebulizing and desolvation gases in electrospray ionization (ESI) and desorption electrospray ionization (DESI) found that the signal responses of compounds of varying sizes and polarities were improved. Here, an expanded selection of nebulizing gases was evaluated to investigate mechanisms of improvement. The set of nebulizing gases included hydrogen, helium, nitrogen, argon, and carbon dioxide. Results indicate that the signal enhancements are achieved by gases lighter than nitrogen and that the previously described helium effects can be improved by using the more economical and sustainable hydrogen as a nebulizing gas. Additionally, H2 and He reduce the desorption footprint, which could be potentially useful in increasing the resolution of chemical imaging microscopy, especially since, despite the smaller footprint obtained using helium and hydrogen, higher signals are obtained compared to nitrogen.