Infusion Nanoelectrospray Ionization Mass Spectrometry

Abstract

This report reviews the introductory aspects of electrospray ionization coupled with mass spectrometry and highlights those aspects of electrospray that play an important role in its application to analyzing real‐world samples. Following a discussion of matrix effects, factors that affect analyte response and sensitivity, and the flow rate factors of the spray solvent, the relative benefits of on‐line HPLC or UPLC are contrasted with an infusion electrospray sample introduction approach, which, of course, precludes any aspects of chromatographic separation. The introduction of samples via infusion bypasses the need for a chromatographic system, including its pumps, autosampler, separation column, and the compromise of a mobile phase, which must accomplish the chromatographic separation while also allowing the electrospray ionization process to occur. Thus, infusion sample introduction is in principle much easier to accomplish. However, there are clear benefits to employing HPLC for the analysis of complex samples. So, how can infusion sample introduction be worthwhile? It can be worthwhile because nanoelectrospray, or electrospray at 20–500 nL/min solvent flow rates, provides some unique benefits over the higher flow rate regime that has been customarily used. Thus, nanoelectrospray provides improved sensitivity, reduced matrix suppression, and normalized response from differing analytes and conserves precious samples if this is an issue. This review overviews these principles and provides several successful examples of published work where infusion nanoelectrospray experiments have merit.