LC–MS with electron ionization of cold molecules in supersonic molecular beams

Abstract

A new approach is described for the combination of electron ionization and LC–MS based on sample ionization as vibrationally cold molecules in a supersonic molecular beam (Cold EI). Cold EI of sample compounds in liquid solutions (methanol, acetonitrile, water, etc.) is achieved through spray formation, followed by soft thermal vaporization of the sample particles prior to their supersonic expansion and direct electron ionization of the sample compounds while they are contained in a supersonic molecular beam (SMB). Cold EI mass spectra were demonstrated to combine an enhanced molecular ion and improved mass spectral information (in comparison with standard EI), plus all the library searchable fragments. Cold EI enables the ionization of a broad range of compounds, including the full range of non-polar samples. Four orders of magnitude linear dynamic range is demonstrated and a detection limit of 2 pg was achieved for a 774 amu compound in single ion monitoring mode at m/ z = 774. The method and apparatus are under continuous development and we feel that it can excel particularly in the analysis of unknown samples, while enabling fast LC–MS analysis through automated mass spectral deconvolution of coeluting LC peaks. In addition, the same MS system can also serve as an advanced GC–MS with supersonic molecular beams.