A Smart DNA Network-Based Diagnostic System for Enrichment and Detection of Circulating Tumor Cells in Cancer Liquid Biopsy

Circulating tumor cells (CTCs) have emerged as critical biomarkers in liquid biopsy for noninvasive tumor diagnosis and real-time monitoring of cancer progression. However, the isolation of CTCs is often required before detection due to their ultralow abundance in peripheral blood. These isolation processes are typically time-consuming and prone to cell loss, which limits the utility of CTC-based liquid biopsy. Herein, we present a DNA network-based diagnostic system that enables specific recognition, selective enrichment, and accurate detection of CTCs directly from blood samples. The DNA network comprises ultralong DNA chains embedded with polyvalent aptamers and fluorescence detection modules. The polyvalent aptamers selectively bind to the epithelial cell adhesion molecule (EpCAM) on a CTC membrane, facilitating their enrichment through base pairing-driven DNA network formation. This system semiquantitatively detects the expression level of cancer-associated microRNA within CTCs using ratiometric fluorescence imaging based on the chemical assembly of two fluorescence modules. In clinical blood samples, this diagnostic system achieves 100% precision and 96% accuracy in distinguishing breast cancer patients from healthy donors, highlighting its promising potential for clinical breast cancer diagnosis.