ABSTRACT Ionic matrices for matrix‐assisted laser desorption/ionization (MALDI) have demonstrated superior performance compared to traditional matrices for profiling and screening of carbohydrate composition. However, their application in MALDI‐MS imaging of N‐glycans in tissues remains elusive, in part due to suboptimal matrix application conditions. In this study, we optimized 2,5‐dihydroxybenzoic acid/N, N‐dimethylaniline (DHB/DMA) ionic matrix spray conditions to enhance the sensitivity of spotted N‐glycan standards; however, these conditions were not suitable for analyzing endogenous N‐glycans in tissue. To address this, we refined the composition of the ionic matrix by replacing DHB with α‐cyano‐4‐hydroxycinnamic acid (CHCA) and DMA with its hydrochloride salt (DMA·HCl), resulting in superior performance compared to the CHCA matrix, which is the most widely used for spatial N‐glycomics. This method enhanced the sensitivity for detecting diverse N‐glycan types, including low‐abundance sialic acid glycans, while maintaining their endogenous location—a key limitation of liquid‐state DMA.
Vandyk et al. (Sun,) studied this question.