Aerosol matrix-assisted laser desorption ionization mass spectrometry

Abstract

Our laboratory has developed a technique that uses a pneumatically generated aerosol to combine liquid introduction with matrix-assisted laser desorption ionization (MALDI) mass spectrometry. The work described here presents detailed studies on the effect of matrix to analyte ratio, analyte concentration, organic solvent type and concentration, salt type and concentration, and trifluoroacetic acid on the ion signal. It was determined that the optimum matrix to analyte ratio is in the range 10-100:1, compared to the 10010,000:1 typically used with surface MALDI. This difference is the result of rapid drying of the aerosol particles in the vacuum of the mass spectrometer, compared to the slowly dried samples used with surface MALDI. The analyte ion signal is non-linearly dependent on the analyte concentration. This is postulated to be a result of the residual solvent present in the aerosol particles. Furthermore, using the studies of ion signal as a function of organic solvent type and concentration, a model for aerosol MALDI is developed. It is postulated that the aerosol particle may not be homogeneous in analyte and matrix, but that the matrix and analyte are separated within the aerosol particle because of differences in hydrophobicities. The studies of ion signal as a function of trifluoroacetic acid indicate that there is an optimum trifluoroacetic acid concentration necessary for analyte ion signal, and this optimum is not the same for all matrices. HPLC using aerosol MALDI as detection is demonstrated. In addition, hydrogen/deuterium exchange using aerosol MALDI is also demonstrated and discussed.