Sensitive and Reproducible SERS Profiling of Tumor-Derived EVs via Uniform Microfluidic Nanobowl Arrays for...

Tumor-derived extracellular vesicles (EVs) are promising liquid biopsy biomarkers, yet their clinical translation is hindered by the trade-off between enhancement and reproducibility of SERS-based detection. Here, we present a microfluidic SERS platform integrating plasmonic nanobowl arrays that simultaneously achieve a high enhancement factor and signal reproducibility. Periodic nanobowl architectures generate consistent plasmonic hotspots, breaking the typical compromise between sensitivity and uniformity. The aptamer-modified chip enables quantification of EV markers and achieved a calculated analytical limit of detection of 2.5 × 103 particles mL-1 for purified cell line EVs and 1.2 × 104 particles mL-1 for ultrafiltration-pretreated plasma. In a pancreatic cancer mouse model, the platform tracked tumor progression longitudinally, with SERS signals correlating with bioluminescence imaging (r > 0.83). In a pilot clinical study, multimarker analysis achieved 93.33% diagnostic accuracy and effectively monitored chemotherapy response (AUC = 0.80-0.96). This robust platform provides a promising tool for EV-based precision oncology.