Host-Guest Self-Assembled Interfacial Nanoarrays for Precise Metabolic Profiling.

Accurate and rapid metabolic profiling of cerebrospinal fluid (CSF) is urgently needed but remains challenging for clinical diagnosis of central nervous system diseases and biomarker discovery. Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) holds promise for metabolic analysis. Its low signal reproducibility, however, severely restricts acquisition of quantitative MS data in clinical practice. Herein, a multifunctional self-assembled AuNPs array (MSANA)-based LDI-MS platform for direct amino acids analysis and metabolic profiling in patient CSF samples is developed. MSANA featuring a highly ordered and closely packed two-dimensional nanostructure permits capture and direct analysis of aromatic amino acids by LDI-MS with high selectivity and micromolar sensitivity. Meanwhile, the MSANA-based LDI-MS platform exhibits excellent reproducibility (RSD < 10%), largely outperforming the direct matrix spotting approach widely used now (RSD < 44%). The platform is successfully used in metabolic profiling of CSF (1 µL) within minutes for discrimination of medulloblastoma patients from non-tumor controls. Taken together, the MSANA-based LDI-MS platform shows potential clinical values toward large-scale metabolic diagnostics and pathogenic mechanism study.