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

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-de...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2019-04, Vol.11 (15), p.13973-13983
Main Authors: Dong, Jiantong, Zhang, Ryan Y, Sun, Na, Smalley, Matthew, Wu, Zipeng, Zhou, Anqi, Chou, Shih-Jie, Jan, Yu Jen, Yang, Peng, Bao, Lirong, Qi, Dongping, Tang, Xinghong, Tseng, Patrick, Hua, Yue, Xu, Dianwen, Kao, Rueihung, Meng, Meng, Zheng, Xirun, Liu, Ying, Vagner, Tatyana, Chai, Xiaoshu, Zhou, Dongjing, Li, Mengyuan, Chiou, Shih-Hwa, Zheng, Guangjuan, Di Vizio, Dolores, Agopian, Vatche G, Posadas, Edwin, Jonas, Steven J, Ju, Shin-Pon, Weiss, Paul S, Zhao, Meiping, Tseng, Hsian-Rong, Zhu, Yazhen
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Immobilized - chemistry
Antibodies, Immobilized - immunology
Biomarkers, Tumor - genetics
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Epithelial Cell Adhesion Molecule - immunology
ErbB Receptors - genetics
Extracellular Vesicles - metabolism
Female
Gene Rearrangement
Humans
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Middle Aged
Nanowires - chemistry
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Protein-Tyrosine Kinases - genetics
Proto-Oncogene Proteins - genetics
RNA, Messenger - metabolism
Silicon - chemistry
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Summary: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.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.9b01406