Multivalent aptamer nanoscaffold cytosensor for glioma circulating tumor cells during Epithelial–Mesenchymal transition

The key factor that causes glioma invasion and metastasis is circulating tumor cells (CTCs) undergoing epithelial–mesenchymal transition (EMT). Effective analysis of EMT-CTCs can provide an important foundation for early detection and prognosis monitoring of glioma, but the changes in the biomarkers of CTCs in different states of EMT make detection difficult. In this study, we developed a multivalent aptamer nanoscaffold-based electrochemical cytosensor (MAS-cytosensor) to efficiently detect EMT-CTCs. The two chains forming the MAS are composed of a specific aptamer detector, a binding region for DNA self-assembly, and a foothold for interface anchoring. When target CTCs exist, the bisaptamer detector on MAS can sensitively identify CTCs and pull them to the electrode surface, generating electrochemical signals. It has been demonstrated that the MAS-cytosensor can not only detect EMT-CTCs sensitively (detection limit of 6 cells/mL in buffer), but also allows for further downstream analysis after release with high viability. Overall, this cytosensor provides a reliable detection solution for CTCs regardless of their EMT status, and provides an efficient method for in-depth study role of the post-EMT CTCs in clinical application and metastasis mechanisms.