Matrix‐enhanced secondary ion mass spectrometry: Effects of aliphatic carboxylic acid matrices on the sensitivity enhancement of biological phospholipids

Abstract

Matrix‐enhanced secondary ion mass spectrometry (ME‐SIMS) is an effective pre‐treatment method for the sensitivity enhancement of large molecules. Recently, matrix‐assisted laser desorption/ionization (MALDI) matrices, which consist of aromatic acids with benzene rings, have been developed using this technique. However, there are several differences in the desorption and ionization processes of SIMS and MALDI. In this study, the sensitivities of phospholipids mixed with aliphatic carboxylic acids were investigated using Bi‐cluster time‐of‐flight SIMS (TOF‐SIMS). Trans‐aconitic acid (tri‐carboxylic acid) and citric acid (hydroxycarboxylic acid) were used as the matrices. 2,5‐Dihydroxybenzoic acid (DHB), which is a typical aromatic MALDI matrix, was selected as the reference matrix. When trans‐aconitic acid and DHB were used as matrices, the secondary ion yields of [M + H]+ and [2 M + H]+ for phospholipids were approximately 10–150 times higher than that of the pristine lipid. For samples with citric acid, the yield enhancements of [M + H]+ and [2 M + H]+ were approximately 400–1000 times higher than those of pristine lipids. Furthermore, the protonated ionization of citric acid was mostly suppressed because of mixture with phospholipids. These results indicate that the matrix effect between phospholipids and the matrix contributes to the sensitivity enhancement of the target molecules. Hence, aliphatic carboxylic acid was equally or more effective than the MALDI matrix for the sensitivity enhancement of phospholipids in Bi‐cluster TOF‐SIMS.