Novel cytosensor for accurate detection of circulating tumor cells based on a dual-recognition strategy and BSA@Ag@Ir metallic-organic nanoclusters

Abstract

Herein, based on a dual-recognition strategy and BSA@Ag@Ir metallic-organic nanoclusters (BSA@Ag@Ir MONs), a highly specific and sensitive cytosensor was developed for detecting circulating tumor cells (CTCs). To amplify current signal, novel BSA@Ag@Ir MONs with outstanding catalytic activity and huge specific surface area were synthesized, and conjugated with hairpin DNA strands as signal probes. Orion carbon black 40 (Ocb40)//AuNPs were firstly used to modify electrode to increase its conductivity and surface area. Moreover, the dual recognition strategy based on DNA proximity effect was designed to improve the specificity of cytosensor. When two capture probes respectively bound to two adjacent membrane markers of target cells, the probes could form the associative toehold through the proximity effect to capture the signal probes. Only CTCs simultaneously expressing two membrane markers could be captured and generate current responses. The developed cytosensor could detect CTCs in the range of 3 - 3 × 10⁶ cells mL^-1 with a detection limit of 1 cell mL^-1. Notably, the cytosensor could accurately identify CTCs even in whole blood. Therefore, this cytosensor has great potential for application in biological science, biomedical engineering and personalized medicine.

Keywords: Circulating tumor cells; Cytosensor; DNA proximity Effect; Dual recognition; Metallic organic nanoclusters.