Design of a nanocytosensor for isolation and electrochemical detection of folate-overexpressed circulating tumor cells

Magnetic nanomaterial-based electrochemical cytosensor holds great promise to tackle the challenges in isolation and detection of circulating tumor cells (CTCs) by the combination of the selectivity of magnetic cell separation with high sensitivity of electrochemical sensing platforms. Herein, by leveraging nanomaterials with L-cysteine and folic acid, we design innovative biomaterials for electrochemical cell detection, with minimal materials and materials manufacturing steps. Folic acid-L-cysteine-capped CoFe2O4 nanoparticles (CCF) are developed to magnetically capture folate-overexpressed tumor cells. Hybrids of L-cysteine-folic acid and silver nanowires (FAgNWs) are synthesized using a green, convenient and template-free approach without any surfactant. Direct immobilization of L-cysteine and folic into silver nanowires hybrids facilitates the electrode preparation and cell detection. The density functional theory and molecular dynamics simulations were also used to provide deep insight into the interaction of silver nanowires with L-cysteine coupled with folic acid (LCFA). An affordable nanocytosensor is proposed for the detection of CTCs by sandwiching the MCF-7 cells captured between CCF and FAgNWs. This nanocytosensor has the low detection limit of 5 MCF-7 cells/mL with the wide dynamic range of 50–106 cells/mL. The presented nanomaterial-based sensing platform is promising for convenient cell isolation and detection.