非小细胞肺癌（non-small cell lung cancer，NSCLC）是最常见的肺癌类型，约占所有肺癌的85%。目前，低剂量电脑断层摄影术和放射线摄影术被认为是诊断肺癌的标准方法。但是，这两种影像学检测假阳性率依然很高。近年来，追踪体液中的分子标记物开始用于NSCLC的早期检测。其中，细胞外囊泡（extracellular vesicles，EVs），尤其是外泌体，成为一种潜在的癌症早期诊断新型生物标志物。
近日，研究人员开发了一种新型集成微流控装置，该装置能够从肺癌患者的尿液中高灵敏度和特异性分离并原位检测肺癌特异性外泌体。该研究发表于Biosensors and Bioelectronics杂志上。该新装置是利用聚甲基丙烯酸甲酯（PMMA）和经过捕获抗体修饰的纳米多孔金纳米簇膜（AuNC）制造的，然后装载第二抗体偶联的金纳米棒探针（AuR），通过暗视野显微镜鉴定并量化肺癌特异性外泌体。由于共振瑞利散射，AuNC-外泌体-AuR复合物产生了显着的散射波长偏移，并提高了散射强度，使LOD低于1000颗粒/ mL的外泌体可以实现超灵敏检测。最后，研究人员用来自肺癌患者和健康对照组的500μL尿液样品验证了该方法，发现能够将早期肺癌患者与健康个体区分开来。因此，外泌体为肺癌早期检测提供了一种有潜力的生物标志物。
推荐阅读原文：
Anintegrative microfluidic device for isolation and ultrasensitive detection of lung cancer-specific exosomes from patient urine.
Exosomes, derived from various biofluids, may serve as potential biomarkers for cancer early detection. Nevertheless, exosome clinical translation remains challenging due to the lack of reliable isolation and detection methods. Herein, we present a novel integrated microfluidic device specifically designed for isolation and in-situ detection of lung cancer-specific exosomes collected from patient"s urine. The new device has been fabricated using polymethyl methacrylate (PMMA) and a nanoporous gold (Au) nanocluster membrane modified with the capture antibody. The second antibody-conjugated Au nanorod probe was then loaded to identify and quantify lung cancer-specific exosomes using a dark field microscope. AuNC-Exosome-AuR complex produces a significant scattering wavelength shift and an improved scattering intensity due to resonance Rayleigh scattering, which enables the ultrasensitive detection of exosomes with a LOD below 1000 particles/mL. The proteomic analysis revealed that the high-purity exosomes has been isolated by the device. We then validated this method with 500 μL urine samples from lung cancer patients and controls, which showed great promise for differentiating early-stage lung cancer patients from healthy individuals. Taken together, the presented method is fast and ultrasensitive and can be easily adapted for the isolation and detection of cancer specific exosomes from other malignant tumors.
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