eMALDI MS and oligonucleotide analysis

Enhanced matrix assisted laser desorption ionization mass spectrometry (eMALDI MS) refers to MALDI MS in which the efficacy of desorption and ionization is enhanced by heat, volatile species, or both, generated from chemical decomposition of additives in the sample of analyte under MALDI conditions. MALDI MS has been widely used for oligonucleotide (ON) analysis. However, two challenges, limited ability to analyze long ONs and low tolerance to trace salts, significantly restrict its applications. We recently proposed the ion pair thermal model for the gas phase ion formation mechanism of MALDI MS. This model predicts an exponential increase in ion yield with plume temperature. Building on this model, we investigated the effects of azobisisobutyronitrile (AIBN), which decomposes under MALDI conditions and generates heat and volatile species, on MALDI performance. We found that the resulting eMALDI MS method provides more reliable analysis of long ONs and exhibits greater tolerance to alkaline salts.