Microsampling and exosome-enriched optical biochip for non-invasive detection of breast cancer exosomes in clinical human tear fluid

Tumor exosome detection is one of the most clinically relevant liquid biopsy methods for non-invasive breast cancer diagnosis. However, conventional methods are often unsuitable for routine use due to large sample requirements, low precision, and complex procedures. To overcome these challenges, we have developed a novel optical biochip that integrates tear collection, exosome enrichment, and detection into a single platform. This biochip requires only 14 μL of tears and employs dual biomarker aptamers for the simultaneous identification and capture of target exosomes, forming sandwich-like complexes. Subsequently, the chip enriches these sandwich complexes through acoustic radiation, enabling separation from interferences and signal amplification. As a result, the biochip exhibits excellent specificity and ultra-high sensitivity for breast cancer cell exosomes, with a detection limit as low as 1.2 × 10²±0.16 × 10² particles/mL and a detection time of approximately 10.42 min. In addition, this optical biochip was used for the first time to detect exosomes related to breast cancer in tears, effectively distinguishing breast cancer patients from healthy donors with 100 % sensitivity and specificity, offering a meaningful approach for on - site breast cancer diagnosis and personalized medical health.