Highly sensitive SERS cytosensor based on catalytic hairpin assembly-mediated zipper-like structures

Circulating tumor cells (CTCs) are cancer biomarkers for the diagnosis at early stage. However, it’s still a great challenge to develop the cytosensor for CTCs detection due to its ultralow counts in human peripheral blood. Herein, a highly sensitive cytosensor based on surface-enhanced Raman scattering (SERS) was developed. The tumor cells were first identified by a strand replacement reaction (SDR) that released the initiator of catalytic hairpin assembly (CHA) reaction. Subsequently, the initiator opened the residue hairpin DNA outside the silver coated gold nanoparticles ( [email protected] NPs). The double strand DNA (dsDNA) CHA products drove the [email protected] NPs towards the same side of dsDNA to form a zipper-like structure. This structure brought about hotspots area for SERS quantitative analysis of A549 tumor cells. The designed cytosensor exhibited good linearity ranging from 10 to 500 cells/mL with a calculated limit of detection (LOD) of 8 cells/mL. A SERS cytosensor with high sensitivity and good reproducibility was obtained in this work. In addition, this research presents a new method for rapid tumor cell detection in biological samples for cancer diagnosis.