Ho Kwun Hei Willis, Lai Huang, Zhang Ruolin, Chen Haitian, Yin Wen, Yan Xijing, Xiao Shu, Lam Ching Ying Katherine, Gu Yutian, Yan JiaXiang, Hu Kunpeng, Shi Jingyu, Yang Mo
Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China.
Department of Hepatic Surgery and Liver Transplantation Center of The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
ACS Sens. 2024 Sep 27;9(9):4860-4869. doi: 10.1021/acssensors.4c01357. Epub 2024 Sep 4.
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 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.
外泌体是一种含有生物分子货物的纳米级细胞外囊泡，越来越被认为是癌症诊断中有前景的非侵入性生物标志物，特别是因其在携带肿瘤特异性分子信息方面的作用。传统的外泌体检测方法面临诸如复杂性、耗时以及需要精密设备等挑战。本研究通过引入一种新型的液滴微流控平台来应对这些挑战，该平台集成了基于表面增强拉曼光谱（SERS）的适体传感器，用于快速、灵敏地检测乳腺癌细胞来源的HER2阳性外泌体。我们的方法利用了在HER2适体和HER2阳性外泌体存在的情况下芯片上盐诱导的金纳米颗粒（GNP）聚集过程，增强了基于热点的SERS信号放大。该平台实现了4.5 log颗粒/毫升的检测限，每个样品的样品到结果时间为5分钟。此外，该平台已成功应用于临床样品的HER2状态检测，以区分HER2阳性乳腺癌患者和HER2阴性乳腺癌患者。高灵敏度、特异性以及对特定肿瘤外泌体进行高通量筛选的潜力，使得这种基于SERS的液滴系统成为早期癌症诊断的潜在液体活检技术。
