Polymerization as a Strategy to Improve Small Organic Matrices for Low-Molecular-Weight Compound Analytics with MALDI MS and MALDI MS Imaging

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) and the corresponding visualizing technique MALDI MS imaging (MSI) are potent and widely used analytical methods in medical and pathological research. In recent years, the investigation of low-molecular-weight compounds (LMWCs) such as metabolites has moved increasingly into the focus. MALDI techniques require a matrix system, and small organic matrices (SOMs) are commonly used. While SOMs offer multiple advantages, such as broad analyte scopes and high ionization efficiencies, they also suffer from drawbacks, e.g., strong background interferences in the low-mass area (<i>m</i>/<i>z</i> < 1000) and low vacuum stability, which is particularly detrimental for LMWC analytics with high vacuum (HV) MALDI MS and MSI. Here, we apply polymerization as a strategy to alleviate these drawbacks while retaining the multiple advantages of SOMs. Vinyl groups were introduced to two SOMs, the state-of-the-art positive mode matrix 2,5-dihydroxybenzoic acid (DHB) as well as one of the few known dual polarity mode matrices, 7-methoxy-1-methyl-9<i>H</i>-pyrido­[3,4-<i>b</i>]­indole (harmine), and radical polymerization was performed to obtain polyethylene-based P­(SOMs) carrying the corresponding SOMs as side chains. Compared to the corresponding SOMs, the synthesized P­(SOMs) maintain optical properties in the solid state and have competitive performances regarding analyte scopes, ionization efficiencies, and dual polarity mode suitability. Additionally, both P­(SOMs) are HV stable (∼10^–7 mbar) and reveal no background interferences in the low-mass area (MALDI-silent). To assess a potential application in a clinical workflow, the P­(SOMs) were applied on breast cancer xenografts and MALDI MSI measurements were carried out, demonstrating their ability to produce and spatially resolve positive and negative tissue-related ions directly from the cancer tissue. Polymerization is shown to be a promising strategy to make state-of-the-art SOMs MALDI silent and vacuum stable and yield easily handled matrices for clinical workflows.