Electrochemically Controlled Atom Transfer Radical Polymerization for Electrochemical Aptasensing of Tumor Biomarkers

Tumor biomarkers are of great value in the liquid biopsy of malignant tumors. In this work, a simple and cost-friendly electrochemical aptasensor was presented for the highly sensitive and selective detection of glycoprotein tumor biomarkers. The DNA aptamer-modified electrode was used as the sensing interface to specifically capture the target glycoprotein tumor biomarkers, to which the alkyl halide initiators for atom transfer radical polymerization (ATRP) were then attached via the esterification crosslinking between the boronic acid group and the cis-dihydroxyl sites of the conjugated oligosaccharide chains on glycoprotein tumor biomarkers followed by the growth of long-chain polymers through electrochemically controlled ATRP (eATRP) to efficiently recruit the ferrocene detection tags. As there are tens to hundreds of cis-dihydroxyl sites on a glycoprotein tumor biomarker for attaching ATRP initiators while each long-chain polymer can recruit hundreds to thousands of ferrocene detection tags, a significantly high current signal can be generated even in the presence of ultralow-abundance targets. Hence, the eATRP-based electrochemical aptasensor is capable of sensitively and selectively detecting glycoprotein tumor biomarkers. Using alpha-fetoprotein as the model target, the limit of detection was demonstrated to be 0.32 pg/mL. Moreover, the aptasensor has been successfully applied to detect glycoprotein tumor biomarkers in human serum samples. In view of its high sensitivity and selectivity, simple operation, and cost-friendliness, the eATRP-based electrochemical aptasensor shows great promise in the glycoprotein-based liquid biopsy of malignant tumors, even at the early stage of development.