Developing semiconductor substrates with superior stability and sensitivity is challenging in surface-enhanced Raman scattering (SERS) research. Here, a snowflake Cu2S@ZIF-67 heterostructure was fabricated using a straightforward method, exhibiting a notable enhancement factor of 9.0 × 109 and a limit of detection (LOD) of 10−14 M for methylene blue (MB). In addition, the Cu2S@ZIF-67 heterostructure substrate demonstrates outstanding homogeneity (relative standard deviation (RSD) = 9.2%) and stability (120 days). Employing Cu2S generates highly sensitive hotspots via an electromagnetic (EM) mechanism, and the growth of ZIF-67 on its surface augments the adsorption capacity and charge transfer capability (chemical mechanism, CM), thereby enhancing the SERS detection sensitivity. Furthermore, the Cu2S@ZIF-67 heterostructure, which was used as a SERS substrate, facilitated the detection of bisphenol A (BPA) with an LOD of 10−11 M. The Cu2S@ZIF-67 heterostructure substrate has excellent selectivity and anti-interference, which is very suitable for BPA detection in complex environment applications. The accuracy of the Cu2S@ZIF-67 heterostructure as a SERS substrate for detecting BPA in real water samples (water bottles, tap water, and pure milk) was confirmed by comparison with high-performance liquid chromatography (HPLC). These results demonstrate that through the rational design of heterostructures can achieve the quantitative and accurate detection of hazardous substances in food and the environment can be achieved.
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