Laser Ionization of Biomolecules in Solution

Many powerful laser based methods are unavailable for the analysis of molecules in solution. Techniques for the analysis of liquids are particularly important for the study of biomolecules, whose natural environment is a water solution. Mass spectrometry is a powerful analytical technique, but liquids and mass spectrometers are fundamentally incompatible. We have developed a technique for laser ionization of biomolecules in solution by applying matrix-assisted laser desorption ionization (MALDI) to liquid aerosols. In the typical MALDI experiment, the analyte biomolecule is deposited from solution onto a metal surface with a 100 to 50,000 molar excess of a suitable matrix, usually a UV absorbing organic acid.1 The solvents are allowed to evaporate and the sample is inserted into the source region of a mass spectrometer. Light from a pulsed laser is absorbed by the matrix causing both ablation of the surface and ionization of the intact biomolecule. In the aerosol MALDI experiment, 2,3 the analyte biomolecule is dissolved in a methanol solution with an ultraviolet absorbing matrix. The aerosol is sprayed into vacuum, desolvated, and ionized by pulsed UV laser radiation. The ions are mass separated in a time-of-flight (TOF) mass spectrometer. Aerosol MALDI mass spectra have been obtained for a variety of peptides and proteins with molecular weights as large as 80,000. We have used aerosol MALDI as a liquid chromatography detection method4 (LC/MS) and as a probe of aerosol and cluster chemistry.5 This paper gives a general description of aerosol MALDI and discusses some recent results for peptide and protein ionization.