A amperometric immunosensor for sensitive detection of circulating tumor cells using a tyramide signal amplification-based signal enhancement system

Herein, tyramide signal amplification (TSA)-based electrochemical immunosensor was exploited for highly sensitive detection of CTCs. In this immunosensor, the nucleolin-targeting aptamer AS1411 (CP) was used to specifically capture tumor cells, and a TSA-based signal enhancement system consisting of Pt NPs@HRP@CP composite as catalytic probe and tyramine functionalized infinite coordination polymer (ICPs@Tyr) as electroactive signal tag was applied to improve the detection sensitivity. Using HeLa cell as the model CTCs, after a sandwich reaction, CP HeLa Pt NPs@HRP@CP bioconjugates were formed on the electrode. Millions of ICPs@Tyr could be layer-by-layer deposited onto the target cell membrane by the catalysis of Pt NPs@HRP@CP. The developed immunorsensor could detect HeLa cell with a wide dynamic range from 2 to 2 x 10(4) cells/mL and a detection limit of 2 cells/mL. Most importantly, the amperometric immunosensor was successfully applied to discriminate tumor cells from white blood cells, exhibiting high specificity and sensitivity. In conclusion, this work demonstrates that the TSA-based signal enhancement system might be a potential alternative tool for the electrochemical measurement of trace amounts of CTCs in clinical diagnosis.