Efficient 2D HOF@Au SERS Substrates Synergized with the G-quadruplex Network-Based Catalytic Amplification Strategy for Low-Background Trimode Detection of Lomefloxacin

In this study, a two-dimensional hydrogen-bonded organic framework (2D HOF) @Au surface-enhanced Raman scattering (SERS) substrate was utilized to be synergistic with the G-quadruplex DNA network (GDN) as a signal catalyst to achieve a low-background trimode detection for lomefloxacin. A large specific surface area and abundant -NH₂ functional groups of 2D HOF serve as an ideal nanocarrier for loading numerous Au nanoparticles, thereby enhancing active site density and generating a strong electromagnetic field. Subsequently, target-induced DNA walkers efficiently cleaved to produce a substantial amount of output DNA, furthered enhancing the selectivity of the sensing system. By designing the terminal regions of DNA strands S2 and S3 as split G-quadruplex motifs and hybridize with output DNA to form a Y-shaped module, which can further self-assemble into a GDN, this network effectively captured a large quantity of hemin, thereby exhibiting robust peroxidase-like activity. Notably, compared to the conventional approaches that employed nanowires as carriers for G-quadruplex structures, the DNA network offered superior structural stability and stable catalytic performance. Moreover, the reconstitution of split G-quadruplex units into intact G-quadruplexes significantly reduced background signals and minimized nonspecific positive responses. Finally, the integration of the G-quadruplex-rich GDN with DNA-functionalized 2D HOF enabled the catalytic conversion of H₂O₂ into ·OH radicals and oxidized TMB to oxTMB, inducing distinct colorimetric and SERS signal changes. This approach enabled the simultaneous SERS, colorimetric, and visual detection of lomefloxacin (LOM) with detection limits as low as 6.54 × 10⁻¹⁴ mol/L, 3.27 × 10⁻¹¹ mol/L, and 5.31 × 10⁻¹¹ mol/L, respectively. This method has been successfully applied to the analysis of real-world samples, demonstrating its promising potential for practical applications.