FlexESI: An Automated Vapor-Switching Interface for Enhanced Flexibility and Sensitivity in Electrospray Ionization.

One of the ways to improve the performance of electrospray ionization (ESI) mass spectrometry (MS) is to introduce additives to the sample solution. Alternatively, such additives can be introduced in the gaseous form directly into the electrospray plume. Normally, only one additive can be introduced via one method. Here, we present a flexible automated system that enables dynamic switching among several gas-phase additives, which can alternately be introduced to the ion source compartment over a short period of time. These additives include vapors of acids and solvents. We show that different gaseous additives enhance the signals of different analytes to a varied extent. The enhancement factors were in the range ∼ 2-15. We applied the gas-phase additive switching in real sample analysis, where it enhanced signal intensities and broadened the detection range. The automated system also enables the dosing of vapors at different concentrations. Unlike conventional approaches that saturate the electrospray plume with a fixed vapor level, controlled dosing of acid or solvent vapor levels enables optimization of the protein signal intensity and facilitates structural probing. Overall, it is possible to systematically vary both the type and the concentration of vapor additives using a single setup, improving the analytical performance and versatility of ESI-MS. The proposed setup is compatible with liquid chromatography.