Boronic Acid Mass Tag Empowered Detection of Glucose for MALDI MS Imaging

Glucose is a key metabolite involved in energy production, biosynthesis, and signaling. The metabolism of glucose is also dysregulated in many diseases, such as cancer, in which metabolic reprogramming of the carbohydrate is a hallmark of malignancy. In spite interest in using mass spectrometry imaging (MSI) to study the spatial temporal concentrations of glucose in normal and diseased tissues, poor ionization efficiency inhibits matrix-assisted laser desorption ionization (MALDI) analysis of the endogenous metabolite. A novel mass tag featuring a diol-targeting boronic acid warhead linked to a positively charged absorbing moiety is reported for on-tissue chemical derivatization to enhance glucose detection sensitivity and ionization efficiency. Spray deposition of the borate mass tag followed by 2,5-dihydroxyacetophenone matrix and MSI acquisition in the positive ion mode gave up to 10-fold greater sensitivity for glucose compared to standard analysis using N-(1-naphthyl)ethylenediamine dinitrate matrix and enabled imaging at 10 and 5 μm spatial resolution on brain tissue, which displayed glucose distribution without delocalization or edge effects. Empowering spatially resolved analysis of glucose metabolism with high sensitivity, boronic acid tag offers strong potential for studying disease-specific metabolic reprogramming.