SERS assay of FTO by coordination modulation of MIL-101(Fe)

It is well established that enhanced substrate serves as a critical determinant for surface enhanced Raman scattering (SERS) performance and chemical enhancement constitutes one of the primary mechanisms, which mainly depends on the intrinsic characteristics of substrates. In this work, we tuned the Fe³⁺ coordination environment and valence state in MIL-101(Fe) by partially replacing terephthalic acid with benzoic acid, creating a defective MOF (BMIL-3). Owing to its abundant oxygen vacancies, active sites, and efficient charge-transfer pathways, BMIL-3 exhibits superior SERS performance toward Rhodamine B (RhB). These findings align with first-principles density functional theory (DFT) simulations, confirming enhanced charge-transfer efficiency in BMIL-3. Further, we developed a highly sensitive catalytic hairpin assembly (CHA)-based fat mass and obesity-associated protein (FTO) biosensor with a 1.66 fM detection limit. This work not only develops a way to synthesize SERS substrates, but also provides a sensitive biosensing platform for detecting biological molecules, offering significant potential for clinical diagnostic.