In situ signal amplification improves the capture efficiency of circulating tumor cells with low expression of EpCAM

• Published in: Analytica chimica acta Vol. 1221; p. 340133
• Main Authors: Chen, Kang, Zhang, Ziyan, Zhu, Xingyuan, Lin, Zhun, Xie, Jinye, Dong, Qian, Fu, Qiang, Zhang, Yuanqing
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-08-2022
• Subjects: Cell enrichment; Circulating tumor cells; DNA nanostructure; Rolling circle amplification; Signal amplification; DNA nanostructure; Circulating tumor cells; Rolling circle amplification; Signal amplification; Cell enrichment
• ISSN: 0003-2670; 1873-4324
• DOI: 10.1016/j.aca.2022.340133

Circulating tumor cells (CTCs) as non-invasive biomarkers have great potential in evaluating tumor progression and prognosis. However, effective enrichment of CTCs and minimizing phenotypic bias remain a serious challenge. Herein, a DNA tetrahedron-aptamer complex-mediated rolling circle amplification (TDN-RCA) strategy is developed for cell surface protein signal amplification and CTC enrichment, employing DNA tetrahedron-EpCAM aptamer complex as a scaffold and initiating rolling circle amplification (RCA) reaction on the surface of CTCs in situ. The DNA tetrahedron-aptamer complex enables the cell-specific recognition and enhances cell membrane anchoring ability, generating a large number of magnetic beads binding sites through the RCA reaction in situ. Thus, the signals of cell surface markers with low expression levels are amplified in situ and then efficient CTC enrichment is achieved. This method improves the capture efficiency of CTCs with low expression of EpCAM, which has great potential in clinical application.
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•A DNA tetrahedron-aptamer complex-mediated rolling circle amplification (TDN-RCA) strategy was established.•The TDN-RCA amplified signals of less expressed membrane protein in situ and achieved efficient enrichment of CTCs.•The TDN-RCA can enhance the capture efficiency and strengthen binding between capture bait and CTCs.•The TDN-RCA can show good capture performance for target cells with different phenotypes.