A living cells-based bionic micro-nano robot for precise electrochemical detection and collection of CTCs

Accurate detection and nondestructive collection of circulating tumor cells (CTCs) remain an enormous challenge due to their extremely low concentration. Herein, an electrochemical cytosensor was developed based on living cell-based bionic micro-nano robots (LCMNRs) and necklace-like AuPt porous hollow nanocomposites (nlAuPt phNCs). The LCMNRs can efficiently cleave D-RNA by the synergistic effect of Mg²⁺-dependent DNAzyme activity and autonomous motility of living cells, and can simultaneously recognize the triple membrane markers of CTCs based on DNA proximity effect. The nlAuPt phNCs, as signal labels, exhibited high specific surface area and multiple excellent enzyme-mimetic activities, particularly prominent electrocatalysis toward H₂O₂. The developed cytosensor demonstrated a superior analytical performance, with a wide linear range (3 to 3 × 10⁵ cells mL^-1) and an exceptionally low detection limit of 1 cell mL^-1. Additionally, it exhibited the capability to distinguish among multiple types of cancer cells and enable the isolation of CTCs while largely maintaining cell viability. The analysis of clinical blood samples confirmed the cytosensor had outstanding anti-interference ability, along with a specificity of 100% and a sensitivity of 86.7%. Collectively, this developed cytosensor holds great promise as a powerful tool for the precise detection of CTCs and the early monitoring of tumor metastasis.