An Amorphous Nanocomposite for Dual-Mode Metabolic Fingerprinting and Diagnosis of Adolescent Depressive Disorder

Adolescent depressive disorder (ADD) is a chronic and debilitating mental disorder, yet its diagnosis still relies on subjective assessment. An efficient and cost-effective diagnostic tool for ADD is urgently needed to improve clinical management. Herein, amorphous MIL-88B@nitrogen/sulfur co-doped carbon-dots (aMIL-88B@NSCDs) are designed as a dual-ion mode matrix for comprehensive metabolic profiling of ADD. The aMIL-88B@NSCDs with integrated physicochemical properties facilitate the efficient dual-ionization of metabolites, enabling the selective ionization of metabolites from bio-samples. It exhibits a 5–12-fold signal enhancement over NSCDs (a well-established dual-ion mode matrix) and shows high reproducibility with coefficients of variation ≤ 10%. Next, we directly extracted the dual-ion mode serum metabolic fingerprints (dual-SMFs) with 432 features (defined as signal-to-noise ratio (S/N) > 3, 190/242 in positive/negative ion mode) within seconds. Based on the dual-SMFs, we constructed a high-performance diagnostic model for ADD, with an area under the curve (AUC) of 0.926 (0.760/0.734 in positive/negative ion mode). This work not only contributes to the development of the dual-ion mode matrices but also provides an efficient and comprehensive strategy for the precision clinical management of ADD.