An electrochemical aptasensor for highly sensitive detection of CEA based on exonuclease III and hybrid chain reaction dual signal amplification

Abstract At present, carcinoembryonic antigen (CEA) is considered a broad-spectrum cancer biomarker, and its accurate analysis in clinical samples can assist early cancer diagnosis and treatment. Herein, a novel electrochemical aptasensor has been proposed for CEA detection based on exonuclease III and hybrid chain reaction. The target CEA specifically binds to the aptamer region in hairpin probe 1 (defined as H1) by strong attraction, which leads the rest of the H1 triggering catalytic hairpin assembly to form a high quantity of H1 and hairpin probe 2 (defined as H2) double chain complex (denoted as H1@H2). Subsequently, the exonuclease III digests the complex of H1@H2 and liberates H1 to induce the first signal amplification. Simultaneously, a large number of generated trigger chains initiate a hybrid chain reaction and produce a second signal amplification. This proposed sensor exhibited excellent analytical performance for the detection of CEA, with wide linear range from 10 pg.mL−1 to 100 ng.mL−1 and low limit of detection of 0.84 pg.mL−1. Additionally, the biosensing strategy was successfully verified for direct measurement of CEA in human serum. Therefore, this elaborated sensor provides a new simple method for detecting CEA and exhibits great promise in the early screening of cancer.