Porous COF@cMOF Heterojunction-Assisted Laser Desorption/Ionization Mass Spectrometry for Enhanced Breast-Cancer Serum Metabolomic Screening.

Jin, Yingxue; Qiu, Pengjun; Wen, Qi; Zhang, Jinni; Liu, Yujing; Sun, Ying; Zheng, Jianping; Zhong, Yanhui et al. · Adv Mater · 2026

basic_science · Level V

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Abstract

Early breast-cancer (BC) screening requires reliable molecular information from minimally invasive samples, yet sensitive detection of small-molecule metabolites in complex biofluids remains challenging. Herein, a structurally well-defined porous heterojunction matrix, COF316@CuHHTP, is developed through an in situ epitaxial-growth strategy for serum metabolomic screening. Porous and chemically robust COF316 serves as the core scaffold, while conductive CuHHTP forms a coherent shell for interfacial charge mediation. The resulting heterojunction enables efficient small-molecule capture and directional transport through the channels, while enhanced photothermal conversion and optimized charge transport collectively improve desorption/ionization efficiency and sensitivity for small-molecule metabolites. Consequently, COF316@CuHHTP enables sensitive and robust laser desorption/ionization mass spectrometry (LDI-MS) analysis, with the maximum signal-to-noise (S/N) enhancement reaching ∼194-fold, ultralow limits of detection (LODs) down to the pmol level, and strong tolerance to high-salt and protein-rich conditions. Applied to serum analysis, this platform enables BC diagnosis with excellent discriminatory performance (AUC = 0.996) and identifies 20 disease-associated metabolic signatures.