Heterojunction-Engineered Mass Spectrometry Platform for Deciphering Serum Metabolic Fingerprints in Diagnosis of...

Respiratory diseases, including bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and lung cancer (LCa), pose a major global health challenge due to overlapping symptoms that frequently delay accurate diagnosis. Although metabolomics-based molecular phenotyping offers a promising path forward, its application in clinical treatment is limited by the use of conventional analytical techniques. Herein, MOF-derived metal oxide/TiO₂ heterojunctions (including ZnTi, FeTi, CrTi, CuTi, and CoTi) are synthesized and evaluated as a nanomatrix for high-throughput laser desorption/ionization mass spectrometry (LDI-MS). CoTi is found to exhibit enhanced laser absorption, suppress charge recombination, improve photothermal desorption, and have a high tolerance to complex biofluids. This platform enables high-quality serum metabolic fingerprints to be acquired from 776 clinical samples, accurately discriminates BA, COPD, ILD, and LCa from healthy controls, and precisely identifies the LCa stages when integrated with machine learning. AUC values of 0.950 and 0.956 are obtained for discovery and validation sets, respectively, across the five-group classification by construction a 23-metabolite diagnostic panel. This study not only introduces a rational heterojunction design strategy for LDI-MS use but also establishes a robust, cost-effective analytical platform bridging nanomaterials with clinical diagnostics, thereby providing a pathway toward metabolomics-driven precision medicine for respiratory diseases.