Matrix-free methods for laser desorption/ionization mass spectrometry

Matrix assisted laser desorption/ionization (MALDI) is a soft ionization mass spectrometric method that has become a preeminent technique in the analysis of a wide variety of compounds including polymers and proteins. The main drawback of MALDI is that it is difficult to analyze low molecular weight compounds (<1,000 m/z) because the matrix that allows MALDI to work interferes in this mass range. In recent years there has been considerable interest in developing laser desorption/ionization (LDI) techniques for the analysis of small molecules. This review examines the approaches to matrix‐free LDI mass spectrometry including desorption/ionization on silicon (DIOS), sol‐gels, and carbon‐based microstructures. For the purposes of this review matrix‐free methods are defined as those that do not require matrix to be mixed with the analyte and therefore does not require co‐crystallization. The review will also examine mechanisms of ionization and applications of matrix‐free LDI‐MS.