Magic matrices for ionization in mass spectrometry

The initial discovery that a heated inlet tube of a mass spectrometer is an ionization source producing ions from volatile, nonvolatile, small, and large molecules with charge states similar to electrospray ionization has been advanced to ionization requiring only the vacuum inherent with a mass spectrometer and a suitable matrix. This spontaneous ionization method was first applicable with the matrix 3-nitrobenzonitrile. Here we report that over 40 compounds have now been discovered that spontaneously convert molecules to gas-phase ions when exposed to sub-atmospheric pressure, some with remarkable sensitivity (10 fmol of protein insulin), The commonality of all matrices is the ability to sublime, preferably near room temperature, through exposure to vacuum, and the ability to create charge separation under these conditions. The effect of vacuum, airflow, temperature (-80 to +150 degrees C) and pH (1-9) on the effectiveness of these newly discovered matrices to ionize peptides and proteins is presented. Compounds with and without acidic hydrogen atoms act as matrices and ionize specific compound classes. The new matrices extend applications from peptides, proteins and drugs to compound classes without basic functionality such as lipids and synthetic polymers in the negative and positive modes. Mass resolution and ion mobility spectrometry aspects are also discussed. (C) 2014 Elsevier B.V. All rights reserved.