A dual-mode microfluidic chip embedded with photoelectrochemical sensing and fluorescence imaging for phenotypic analysis of tumor cells.

Circulating tumor cells (CTCs) in peripheral blood are a heterogeneous population responsible for tumor metastasis. Therefore, the isolation of CTCs and precise analysis of their phenotypes are crucial for early cancer diagnosis and effective treatment. In this study, we developed an integrated microfluidic chip capable of efficiently isolating CTCs from whole blood and performing dual-mode detection using near-infrared photoelectrochemical (PEC) aptasensors and fluorescence imaging. This dual-mode strategy enhances phenotypic screening and improves detection accuracy. The chip features a herringbone-shaped microfluidic channel coupled with a PEC sensing system based on Yb-BiS@AuNPs nanocomposites, which serve as photoelectric conversion elements, and an aptamer-functionalized surface for CTC capture. Utilizing a "rail transit" principle, different CTC phenotypes were selectively captured and screened based on spatial effects. Following capture, the CTCs were labeled with a hemicyanine fluorescent probe for fluorescence imaging. The system achieved a tumor cell separation efficiency of up to 90 %. The combination of PEC aptasensor sensitivity and fluorescence imaging ensures the high accuracy of tumor cell detection. This dual-mode system provides both highly sensitive PEC-based detection and fluorescence-based cell counting, enabling the phenotypic screening and quantification of CTCs with exceptional performance.