Examining Plasma Polymer-Coated Indium Tin Oxide Slides to Enhance Analyte Detection in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging

Abstract

Analyte delocalization is a significant challenge in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). In this study, we present a novel approach to decrease this phenomenon and improve analyte detection by modifying the wettability of indium tin oxide (ITO)-coated glass slides, commonly used for tissue analysis, using plasma polymer coatings. These coatings are stable under vacuum conditions and during the ionization process. Surface coatings had minimal impact on the signal-to-noise ratio of peptides, proteins, and lipids in profiling experiments, where analytes were directly spotted on the surface, but it had a pronounced effect in MALDI MSI. When analyzing fresh-frozen murine brain sections, the highly hydrophobic pPFO coating reduced analyte delocalization and improved the detection of m/z features and lipids compared to uncoated ITO slides. This enhancement was likely due to better preservation of native spatial distribution during tissue-dependent extraction and retention. Notably, cholesterol, a critical analyte in brain research, was easily detected. This study marks the first application of plasma polymers to modify ITO slides for MALDI MSI, resulting in a significant enhancement of localized lipid ion intensity, particularly in the context of high-resolution MALDI-2.