Capillary-SERS Sensor Based on Aptamer-Mediated Inhibition of Nanozyme Catalysis for Ultrasensitive Detection of Homocysteine in Serum from Hepatocellular Carcinoma Patients

Abstract

Early detection and sensitive monitoring of homocysteine (Hcy) in serum are crucial for liver cancer screening. Here, we developed a capillary-based SERS sensor utilizing aptamer capture of Hcy and the highly catalytic properties of nanozymes to achieve ultrasensitive detection of Hcy in liver cancer serum. This sensor features ordered assembly of Au@ZIF-8, which possesses both nanozyme activity and SERS enhancement effects, on the inner wall of an amino-treated capillary. Hcy aptamers were then surface-modified to enable specific recognition. In the presence of H 2 O 2 , Au@ZIF-8 catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to form an oxidized product (ox-TMB) exhibiting strong SERS response. When Hcy is present, it suppresses the catalytic process by scavenging reactive free radicals in the reaction system, leading to a significant attenuation of the SERS signal. Based on this signal-modulation mechanism, the sensor demonstrates exceptional detection performance with a limit of detection reaching the pM range. In authentic clinical samples, it effectively distinguishes HCC patients from healthy individuals, showing strong correlation with ELISA results. Diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curve analysis, yielding an AUC of 0.9063. These findings indicate promising applications for the sensor in early HCC diagnosis and biomarker detection.