Lateral resolution in NALDI MSI: back to the future

Nanostructure-assisted laser desorption/ionization (NALDI) has been recognized as a powerful matrix-free mass spectrometry tool ideal for imaging of small molecules. In this report, the NALDI approach was compared with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry in terms of sensitivity, reproducibility, and lateral resolution, which can be achieved in mass spectrometry imaging (MSI) experiments using a Nd:YAG laser. Scanning electron microscopy was used for surface topology analysis and evaluation of a putative surface-enhanced sensitivity effect, which was observed upon reduction of the laser focus. NALDI was identified as a more reproducible technique lacking MSI artifacts arising from distant tissue removal known from MALDI oversampling.