Laserspray ionization-ion mobility spectrometry-mass spectrometry: baseline separation of isomeric amyloids without the use of solvents desorbed and Ionized directly from a surface.

The ability of laserspray ionization (LSI) to produce multiply charged ions by laser ablation from the solid state, directly from a surface, and at atmospheric pressure allows protein analysis on an ion mobility spectrometry (IMS)-mass spectrometry (MS) instrument (SYNAPT G2) having a mass-to-charge limit of 8000. The matrix, 2,5-dihydroxyacetophenone, lowers the thermal requirements for desolvation of matrix/analyte clusters to produce the highly charged LSI ions under gentle conditions to retain structural integrity of the proteins. Examples include cytochrome C and lysozyme. The solvent-free IMS gas-phase separation is used to baseline separate in the drift time dimension the isomeric solubility restricted β-amyloid (1-42) from the reversed (42-1). The LSI process is shown to be sufficiently soft to preserve structural integrity and permit separation according to the different shapes. These results suggest that LSI-IMS-MS potentially combines speed of analysis and imaging capability common to matrix-assisted laser desorption/ionization and multiple charging with the potential for structural analysis common to electrospray ionization.