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The Exosome Total Isolation Chip

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† ‡ Canary Center at Stanford for Cancer Early Detection, Department of Radiology, School of Medicine, Department of Radiology, School of Medicine, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Department of Pediatrics, School of Medicine, #Department of Materials Science and Engineering, Department of Medicine, and Department of Bioengineering, Stanford University, Stanford, California 94304, United States
§ 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
α Department of Pharmacology & Toxicology, and Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, Michigan 48824, United States
β Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, United States
$ Stanford PULSE Institute, SLAC National Accelerator Lab, Menlo Park, California 94025, United States
γ Hard X-ray Department, LCLS, SLAC National Accelerator Lab, Menlo Park, California 94025, United States
Cite this: ACS Nano 2017, 11, 11, 10712–10723
Publication Date (Web):November 1, 2017
https://doi.org/10.1021/acsnano.7b04878
Copyright © 2017 American Chemical Society

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    Abstract

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    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.

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