Magnetic COF on MOF heterojunction assisted surface-enhanced Raman spectroscopy for 17β-estradiol analysis

17β-estradiol (E2) is a crucial estrogen that significantly influences reproductive biological processes and the development of associated diseases, highlighting the need for effective detection methods. Here, we propose a magnetic hierarchical porous material (Mag MOF@COF-Apt) through the in situ growth of a TAPB-DMTP-COF layer on a magnetic Fe-MOF core for the selective recognition and surface-enhanced Raman scattering (SERS) analysis of E2. The Mag MOF@COF-Apt features the inherent SERS-enhancing properties of Mag MOFs. Furthermore, the COF layer establishes a gap between E2 and the Mag MOF, enhancing SERS activity through the on-shell-isolated effect. Additionally, the topological structure of the COF on the MOF provides a high surface area platform for more affinity sites, and its expanded porous structure facilitates size-exclusion of interferents. Finally, E2 aptamer functionalization equips this heterojunction with the capability for the selective capture of E2. Through these multiple synergistic effects, the Mag MOF@COF-Apt assisted E2 profiling features good sensitivity (detection limit of 110.14 nmol L −1 ), strong tolerance to protein (40 mg mL −1 BSA, 40 mg mL −1 HSA) and salt (40 mg mL −1 NaCl) interference, high signal reproducibility (RSD = 7.29 %) and reusability over four cycles. The effectiveness of Mag MOF@COF-Apt based profiling was validated by successful E2 detection in human serum. This work is anticipated to advance MOF/COF hybrid substrates for SERS, providing an effective tool for E2 analysis.