Laser desorption/ionization mass spectrometry of peptides and proteins with particle suspension matrixes

Systematic investigations of particle suspensions for the laser desorption/ionization of peptides and proteins are presented. The performance and suitability for time-of-flight mass spectrometry of different particle materials and sizes, suspended in a variety of different liquids, are described. Performance characteristics such as accessible mass range, achievable mass resolution, analytical sensitivity, and fragmentation are reported. For the desorption of peptides and small proteins, nanoparticle suspensions in glycerol were found to perform comparably to UV-MALDI-MS with common "chemical" matrixes. For proteins in the mass range of ∼12-30 kDa, mass resolution and analytical sensitivity decrease sizeably; for proteins with masses in excess of ∼30 kDa, no spectra could be recorded with any of the tested particle/liquid combinations. The results were found to be largely independent of the laser wavelength in the range from the near-UV to the near-IR because of the strong particle absorption throughout this wavelength range. Ions are shown to originate predominantly from analyte molecules adsorbed at the particle surface. Nanoparticles with a diameter of a few nanometers were found to be superior to microparticles of ∼1 μm diameter or above. Thermodynamic modeling suggests that this different behavior is caused by the different achieved peak temperatures of the two particle sizes.