Helium assisted desorption and spray ionization

Abstract

We introduce a new method, helium assisted desorption ionization, that uses helium as nebulizing gas in desorption electrospray ionization (DESI). We also investigate Helium Assisted Spray Ionization, when helium is used with a micro-electrospray ionization source similar to electrosonic spray ionization (ESSI). In both methods, analyte ion signals are improved, while the undesirable effects of species created by the breakdown products of atmospheric gases and helium are suppressed. Restriction provided by the extended ion inlet capillary reduces the influx of helium, preventing a deleterious increase in operating pressure in the intermediate ion transfer region. We demonstrate significant improvements in signal intensities for analytes of different sizes and polarities, including xanthine alkaloids, lipids, and proteins. Compared to regular DESI, ion intensities for both protein and small molecules increased with helium addition, while less-polar small molecules were improved to a greater extent. The improvements in signal response with helium nebulization generally followed the same trend using either helium assisted desorption or spray ionization, although the extent of improvement was more substantial in the desorption experiments. This observation suggests that desorption, ionization, and/or ion transport processes could be positively influenced when helium is used as nebulizing gas. Nebulization with helium also produces a smaller desorption footprint compared to nitrogen, promising benefits for chemical microscopy and other applications of DESI-MS.