Tumor-cell detection, labeling and phenotyping with an electron-doped bifunctional signal-amplifier

Cancer cell enumeration and phenotyping can predict the prognosis and the therapy efficacy in patients, yet it remains challenging to detect the rare tumor cells. Herein, we report an octopus-inspired, bifunctional aptamer signal amplifier-based cytosensor (OApt-cytosensor) for sensitive cell analysis. By assembling high-affinity antibodies on an electrode surface, the target cells could be specifically captured and thus been sandwiched by the cell surface marker-specific DNA aptamers. These on-cell aptamers function as electrochemical signal amplifiers by base-selective electronic doping with methylene blue. Such a sandwich configuration enables highly sensitive cell detection down to 10 cells/mL (equal to ~1-2 cells at a sampling volume of 150 μL), even in a large excess of nontarget blood cells. This approach also reveals the cell-surface markers and tracks the cellular epithelial-to-mesenchymal transition induced by signaling regulators. Furthermore, the electron-doped aptamer shows remarkable cell fluorescent labeling that guides the release of the captured cells from electrode surface via electrochemistry. These features make OApt-cytosensor a promising tool in revealing the heterogeneous cancer cells and anticancer drug screening at the single-cell level.