SERS-Based Droplet Microfluidic Platform for Sensitive and High-Throughput Detection of Cancer Exosomes
Kwun Hei Willis Ho, Huang Lai, Ruolin Zhang, Haitian Chen, Wen Yin, Xijing Yan, Shu Xiao, Ching Ying Katherine Lam, Yutian Gu, Jiaxiang Yan, Kunpeng Hu, Jingyu Shi, Mo Yang
Abstract
Exosomes, nanosized extracellular vesicles containing biomolecular cargo, are increasingly recognized as promising noninvasive biomarkers for cancer diagnosis, particularly for their role in carrying tumor-specific molecular information. Traditional methods for exosome detection face challenges such as complexity, time consumption, and the need for sophisticated equipment. This study addresses these challenges by introducing a novel droplet microfluidic platform integrated with a surface-enhanced Raman spectroscopy (SERS)-based aptasensor for the rapid and sensitive detection of HER2-positive exosomes from breast cancer cells. Our approach utilized an on-chip salt-induced gold nanoparticles (GNPs) aggregation process in the presence of HER2 aptamers and HER2-positive exosomes, enhancing the hot spot-based SERS signal amplification. This platform achieved a limit of detection of 4.5 log 10 particles/mL with a sample-to-result time of 5 min per sample. Moreover, this platform has been successfully applied for HER2 status testing in clinical samples to distinguish HER2-positive breast cancer patients from HER2-negative breast cancer patients. High sensitivity, specificity, and the potential for high-throughput screening of specific tumor exosomes make this SERS-based droplet system a potential liquid biopsy technology for early cancer diagnosis.