Signal decay and recovery in matrix-assisted laser desorption/ionization and the thermal model

In matrix-assisted laser desorption/ionization (MALDI), as a UV laser continuously irradiates the same spot on a sample and before the sample is completely depleted, the ion signals decrease as the number of laser shots increases. This prevents the complete usage of the sample and decreases the detection sensitivity of MALDI. In this study, we investigated this phenomenon by conducting experiments involving four commonly used matrices: α-cyano-4-hydroxycinnamic acid (CHCA), sinapinic acid (SA), ferulic acid (FA), and 2,5-dihydroxybenzoic acid (2,5-DHB). As the number of laser shots increased, the numbers of ions desorbed from CHCA, SA, and FA decreased much faster than that desorbed from 2,5-DHB. No decrease in photon absorption was observed, but the decrease in the number of desorbed ions was accompanied by a decrease in the number of desorbed neutrals, an increase in the ratio of analyte to matrix ions, a decrease in surface temperature, and changes in the UV fluorescence spectra. These results suggest photochemical products were generated on the surfaces of the samples. These photochemical products have smaller UV absorption cross sections than do the original molecules, resulting in the aforementioned decreases in surface temperature and the numbers of desorbed ions and neutrals. These changes can be described in terms of the thermal model of MALDI. The photochemical products can be removed by a single high-fluence laser shot, and the ion signals can be partially recovered. The possible photochemical products of the reactions involved in MALDI are discussed herein.