Electrophoresis-enhanced paper spray mass spectrometry

The development of ambient ionization methods, such as paper spray (PS), has streamlined the transition from a collection of molecules in a condensed-phase sample to the gas-phase ions represented in a mass spectrum. In many cases, time and resources are saved by omitting chromatography and sample preparation; yet this strategy also eliminates the opportunity to process mixtures in the condensed phase. We here report a PS method that, without additional hardware or expertise, enhances mass spectrometry (MS) analysis of mixtures through electrophoresis. By loading analyte solution onto pre-wetted paper and applying spray potential, analytes were spatiotemporally processed according to their electrophoretic mobility before being subjected to MS. The fundamental and analytical aspects of this electrophoresis-enhanced PS (EePS) were probed with polarity switching, pH changes, complex environmental matrices, and a variety of analytes, including natural products obtained directly from plant material, without chromatography. EePS provides only modest separations but exhibits wide pH tolerance, high compatibility with complex environmental matrices, excellent robustness, superb cost-effectiveness, and is amenable to novel mass analysis strategies using portable mass spectrometers in situ.