Microfluidic chip coupled with photoelectrochemical/fluorescence dual-modal sensing system for the efficient enrichment and detection of circulating tumor cells

Conventional percutaneous lung biopsy and imaging modalities are often associated with adverse effects and may yield false-negative results, limiting their clinical efficacy. Circulating tumor cells (CTCs) are pivotal mediators in early tumorigenesis and metastatic dissemination. The detection of CTCs offers unparalleled advantages for early diagnosis and metastasis monitoring. NCI–H460 and NCI–H1650 cell lines serve as representative models for non-small cell lung cancer (NSCLC) and are critical biomarkers given that NSCLC accounts for over 85 % of lung cancer cases. Effective enrichment and precise identification of CTCs from whole blood are essential for early diagnostic applications. Herein, a microfluidic platform integrated with a dual-modal detection system, comprising photoelectrochemical (PEC) sensing and fluorescence imaging, was fabricated for the enrichment and quantification of CTCs (NCI–H460 and NCI–H1650 cells). The Hcy-Thiol probe-labeled CTCs in whole blood were separated by a microfluidic chip, and then a cathodic photoelectrochemical sensing system based on different aptamer-modified CuInS₂ nanoflowers was used to selectively capture CTCs and provide photocurrent signals, thus achieving fluorescence/photoelectrochemical dual-mode detection. Under the optimized conditions, the separation efficiency and purity of CTCs were 83.4 % and 76.8 %, respectively. Quantitative analysis of spiked blood samples at 100 cells/mL yielded cell counts of 107 ± 5 NCI–H460 cells and 87 ± 4 NCI–H1650 cells via photocurrent responses, corroborated by fluorescence signals with counts of 110 ± 4 and 85 ± 3 cells/mL, respectively. This microfluidic integrated with PEC/fluorescence dual-modal sensing system exhibits promising potential for early NSCLC detection and metastasis evaluation with high specificity and sensitivity.