Plasmonic Gold Nanoshell-Assisted Laser Desorption/Ionization Mass Spectrometry for Small-Biomolecule Analysis and Tissue Imaging

Plasmonic nanoshells have been acknowledged as efficient nanomaterials for laser desorption/ionization mass spectrometry (LDI-MS) detection of a wide range of small molecules, whereas their applications in mass spectrometry imaging (MSI) are less developed. In this work, we constructed and optimized SiO2@Au nanoshells with tailor-made shell structures and compositions for high-sensitivity LDI-MS analysis and a wide range of MSI applications. Owing to the synergistic effects of plasmonic shells with nanoscale roughness and specific crevice space for the selective trapping of small molecules and cations, SiO2@Au core–shell nanoparticles exhibit superior performance for the detection of a vast diversity of small molecules, including amino acids, oligosaccharides, dyestuff and drugs, peptides, nucleosides, and poly(ethylene glycols). Compared with organic matrices, this method affords a high reduction in matrix interference, higher analyte coverage, lower detection limits ranging from fmol to pmol, and good repeatability with relative standard deviation (RSD) below 5%. Due to the nanoscale size and homogeneous deposition of SiO2@Au nanoshells, the spatial distribution of various small-molecule metabolites can be visualized in strawberry tissues at a pixel size of 100 μm without imaging artifacts. More valuably, the universality of SiO2@Au-assisted LDI-MSI is further demonstrated for mapping the lipid distribution within the whole-body tissues of zebrafish (Danio rerio), honeybees (Apis cerana), and mouse brain tissues in a spatially resolved manner at pixel sizes of 55, 30, and 50 μm, respectively. These results facilitate the expansion of the abilities of plasmonic core–shell nanoparticles in real-case MSI applications. Taken together, the results indicate that the SiO2@Au nanoshells are expected to be promising and efficient nanomaterials with superior DI efficiency and imaging capabilities, especially in the environmental science and life science fields.