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ACS Appl Mater Interfaces. 2019 Apr 17;11(15):13973-13983. doi: 10.1021/acsami.9b01406. Epub 2019 Apr 2.

Bio-Inspired NanoVilli Chips for Enhanced Capture of Tumor-Derived Extracellular Vesicles: Toward Non-Invasive Detection of Gene Alterations in Non-Small Cell Lung Cancer.

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Beijing National Laboratory for Molecular Sciences, MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering , Peking University , Beijing 100871 , P. R. China.
Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics , Chinese Academy of Sciences , Suzhou 215123 , P. R. China.
Institute of Pharmacology , National Yang-Ming University , Taipei 112 , Taiwan.
Samuel Oschin Comprehensive Cancer Institute , Cedars-Sinai Medical Center , Los Angeles , California 90048 , United States.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research , Nankai University , Haihe Education Park, 38 Tongyan Road , Tianjin 300353 , P. R. China.
Department of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine , Guangdong Provincial Academy of Chinese Medical Sciences , Guangzhou 510120 , P. R. China.
Division of Cancer Biology and Therapeutics, Departments of Surgery, Biomedical Sciences and Pathology and Laboratory Medicine , Samuel Oschin Comprehensive Cancer Institute , Los Angeles , California 90048 , United States.
Department of Mechanical and Electro-Mechanical Engineering , National Sun Yat-Sen University , Kaohsiung 80424 , Taiwan.


Tumor-derived extracellular vesicles (EVs) present in bodily fluids are emerging liquid biopsy markers for non-invasive cancer diagnosis and treatment monitoring. Because the majority of EVs in circulation are not of tumor origin, it is critical to develop new platforms capable of enriching tumor-derived EVs from the blood. Herein, we introduce a biostructure-inspired NanoVilli Chip, capable of highly efficient and reproducible immunoaffinity capture of tumor-derived EVs from blood plasma samples. Anti-EpCAM-grafted silicon nanowire arrays were engineered to mimic the distinctive structures of intestinal microvilli, dramatically increasing surface area and enhancing tumor-derived EV capture. RNA in the captured EVs can be recovered for downstream molecular analyses by reverse transcription Droplet Digital PCR. We demonstrate that this assay can be applied to monitor the dynamic changes of ROS1 rearrangements and epidermal growth factor receptor T790M mutations that predict treatment responses and disease progression in non-small cell lung cancer patients.


EGFR T790M mutation; ROS1 rearrangements; extracellular vesicles; microfluidics; nanosubstrates; non-small cell lung cancer

[Available on 2019-10-17]

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