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

ABSTRACT 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 ( a MIL‐88B@NSCDs) are designed as a dual‐ion mode matrix for comprehensive metabolic profiling of ADD. The a MIL‐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.