School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University , Wenzhou, Zhejiang 325035, China.
Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences , Wenzhou, Zhejiang 325001, China.
ACS Nano. 2017 Nov 28;11(11):10712-10723. doi: 10.1021/acsnano.7b04878. Epub 2017 Nov 1.
Circulating tumor-derived extracellular vesicles (EVs) have emerged as a promising source for identifying cancer biomarkers for early cancer detection. However, the clinical utility of EVs has thus far been limited by the fact that most EV isolation methods are tedious, nonstandardized, and require bulky instrumentation such as ultracentrifugation (UC). Here, we report a size-based EV isolation tool called ExoTIC (exosome total isolation chip), which is simple, easy-to-use, modular, and facilitates high-yield and high-purity EV isolation from biofluids. ExoTIC achieves an EV yield ∼4-1000-fold higher than that with UC, and EV-derived protein and microRNA levels are well-correlated between the two methods. Moreover, we demonstrate that ExoTIC is a modular platform that can sort a heterogeneous population of cancer cell line EVs based on size. Further, we utilize ExoTIC to isolate EVs from cancer patient clinical samples, including plasma, urine, and lavage, demonstrating the device's broad applicability to cancers and other diseases. Finally, the ability of ExoTIC to efficiently isolate EVs from small sample volumes opens up avenues for preclinical studies in small animal tumor models and for point-of-care EV-based clinical testing from fingerprick quantities (10-100 μL) of blood.
循环肿瘤衍生细胞外囊泡 (EVs) 已成为鉴定癌症生物标志物以进行早期癌症检测的有前途的来源。然而，EV 的临床应用迄今为止受到限制，因为大多数 EV 分离方法繁琐、非标准化，并且需要大型仪器，如超速离心 (UC)。在这里，我们报告了一种基于大小的 EV 分离工具，称为 ExoTIC（外泌体总分离芯片），它简单、易用、模块化，并且有利于从生物流体中高效、高纯度地分离 EV。ExoTIC 的 EV 产量比 UC 高约 4-1000 倍，并且两种方法之间 EV 衍生蛋白和 microRNA 水平具有良好的相关性。此外，我们证明 ExoTIC 是一个模块化平台，可根据大小对癌细胞系 EV 的异质群体进行分类。此外，我们利用 ExoTIC 从癌症患者的临床样本中分离 EV，包括血浆、尿液和灌洗液，证明了该设备广泛适用于癌症和其他疾病。最后，ExoTIC 能够从小样本量中高效分离 EV，为小动物肿瘤模型中的临床前研究以及从指尖量（10-100 μL）的血液进行基于 EV 的即时护理临床测试开辟了途径。
