The accurate detection of hydrogen peroxide (HO)-involved metabolites plays a significant role in the early diagnosis of metabolism-associated diseases, whereas most of current metabolite-sensing systems are often hindered by low sensitivity, interference of coexisting species, or tedious preparation. Herein, an electrochemistry-regenerated surface-enhanced Raman scattering (SERS) sensor was developed to serve as a universal platform for detecting HO-involved metabolites. The SERS sensor was constructed by modifying newly synthesized 2-mercaptohydroquinone (2-MHQ) molecules on the surface of gold nanoparticles (AuNPs) that were electrochemically predeposited on an ITO electrode. Metabolites were detected through the changes in the SERS spectrum as a result of the reaction of 2-MHQ with HO induced by the metabolites. Combining the superiority of SERS fingerprint identification and the specificity of the related enzymatic reactions producing HO, the designed SERS sensor was highly selective in detecting glucose and uric acid as models of HO-involved metabolite with limits of detection (LODs) of 0.159 μM and 0.0857 μM, respectively. Moreover, the sensor maintained a high SERS activity even after more than 10 electrochemical regenerations within 2 min, demonstrating its effectiveness for the rapid detection of various metabolites with electrochemistry-driven regulation. Importantly, the presented SERS sensor showed considerable practicability for the detection of metabolites in real serum samples. Accordingly, the SERS sensor is a new detection platform for HO-involved metabolites detection in biological fluids, which may aid the early diagnosis of metabolism-related diseases.
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