Metal-Anchored Silicon-Based Nanostructures Enable Dual-Polarity SALDI-MS Analysis of Small Molecules

Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) is an attractive technique for small molecule analysis, because of its low background interference and high throughput. However, the performance of SALDI-MS is strongly dependent on substrate design, and the simultaneous realization of dual-polarity ionization, high reproducibility, and high-throughput capability remains challenging. Herein, we report an ordered silicon-based nanostructure array chip anchored with gold nanoparticles (VSiNW-Au) as an efficient SALDI-MS substrate for small-molecule analysis. The uniform anchoring of gold nanoparticles on silicon nanowire arrays affords low background interference, enhanced ionization efficiency, and improved reproducibility, while supporting dual-polarity SALDI-MS analysis under both positive and negative ion modes. The hydrophobic array architecture, combined with automated mass spectrometry data acquisition, enables rapid analysis of up to 60 samples within 10 min. The performance of the VSiNW-Au platform is demonstrated by detecting perfluoroalkyl and polyfluoroalkyl substances (PFAS) in spiked water samples and by comprehensive profiling of metabolites and lipids in serum. These results highlight the potential of the VSiNW-Au array chip as a robust and high-throughput SALDI-MS platform for rapid screening applications in environmental and biological analysis.