Assessing the potential of sputtered gold nanolayers in mass spectrometry imaging for metabolomics applications.

Mass spectrometry imaging (MSI) is a molecular imaging technique that maps the distribution of molecules in biological tissues with high spatial resolution. The most widely used MSI modality is matrix-assisted laser desorption/ionization (MALDI), mainly due to the large variety of analyte classes amenable for MALDI analysis. However, the organic matrices used in classical MALDI may impact the quality of the molecular images due to limited lateral resolution and strong background noise in the low mass range, hindering its use in metabolomics. Here we present a matrix-free laser desorption/ionization (LDI) technique based on the deposition of gold nanolayers on tissue sections by means of sputter-coating. This gold coating method is quick, fully automated, reproducible, and allows growing highly controlled gold nanolayers, necessary for high quality and high resolution MS image acquisition. The performance of the developed method has been tested through the acquisition of MS images of brain tissues. The obtained spectra showed a high number of MS peaks in the low mass region (m/z below 1000 Da) with few background peaks, demonstrating the ability of the sputtered gold nanolayers of promoting the desorption/ionization of a wide range of metabolites. These results, together with the reliable MS spectrum calibration using gold peaks, make the developed method a valuable alternative for MSI applications.