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ABSTRACT Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. The pathophysiological roles and clinical value

of EVs are under intense investigation, yet most studies are limited by technical challenges in the isolation of nanoscale EVs (nEVs). Here, we report a lipid-nanoprobe system that enables

spontaneous labelling of nEVs for subsequent magnetic enrichment in 15 minutes, with isolation efficiency and cargo composition similar to what can be achieved by the much slower and bulkier

method of ultracentrifugation. We also show that this approach allows for downstream analyses of nucleic acids and proteins, enabling the identification of _EGFR_ and _KRAS_ mutations

following nEV isolation from the blood plasma of non-small-cell lung-cancer patients. The efficiency and versatility of the lipid-nanoprobe approach opens up opportunities in point-of-care

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SIMILAR CONTENT BEING VIEWED BY OTHERS RAPID PURIFICATION AND MULTIPARAMETRIC CHARACTERIZATION OF CIRCULATING SMALL EXTRACELLULAR VESICLES UTILIZING A LABEL-FREE LAB-ON-A-CHIP DEVICE Article

Open access 25 October 2023 MODELING AND OPTIMIZATION OF PARALLELIZED IMMUNOMAGNETIC NANOPORE SORTING FOR SURFACE MARKER SPECIFIC ISOLATION OF EXTRACELLULAR VESICLES FROM COMPLEX MEDIA

Article Open access 16 August 2023 APPLICATION OF PEPTIDES WITH AN AFFINITY FOR PHOSPHOLIPID MEMBRANES DURING THE AUTOMATED PURIFICATION OF EXTRACELLULAR VESICLES Article Open access 30

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lipid-based nanoprobes. _figshare_http://dx.doi.org/10.6084/m9.figshare.4728856 (2017). Download references ACKNOWLEDGEMENTS S.-Y.Z. thanks the Penn State Materials Research Institute, the

Huck Institute of Life Sciences, the Penn State Hershey Cancer Institute, the Penn State proteomic and mass spectrometry facilities at Hershey and University Park, the Penn State Microscopy

and Cytometry Facility, and the Penn State Genomics Facility for their support. This work was partially supported by the Pennsylvania State University start-up fund and the National Cancer

Institute of the National Institutes of Health under Award Number DP2CA174508. We thank the Applied Bioinformatics Center (BFX) at the New York University (NYU) School of Medicine for

providing bioinformatics support and for helping with the analysis and interpretation of the data. This work used computing resources at the High Performance Computing Facility (HPCF) of the

Center for Health Informatics and Bioinformatics at the NYU Langone Medical Center. We also thank the Genome Technology Center (GTC) for library preparation and sequencing. This shared

resource is partially supported by the Cancer Center Support Grant, P30CA016087, at the Laura and Isaac Perlmutter Cancer Center. We would like to thank S. Hafenstein at Penn State Hershey

for discussions on cryo-SEM and C. Zhang at the Dana-Farber Cancer Institute for his advice on genomic analysis. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biomedical

Engineering, Micro and Nano Integrated Biosystem (MINIBio) Laboratory, The Pennsylvania State University, University Park, 16802, Pennsylvania, USA. Yuan Wan, Gong Cheng, Si-Jie Hao, Merisa

Nisic, Chuan-Dong Zhu, Yi-Qiu Xia, Wen-Qing Li, Zhi-Gang Wang, Wen-Long Zhang & Si-Yang Zheng * Penn State Materials Research Institute, The Pennsylvania State University, University

Park, 16802, Pennsylvania, USA. Yuan Wan, Gong Cheng, Si-Jie Hao, Yi-Qiu Xia, Wen-Qing Li, Zhi-Gang Wang, Wen-Long Zhang & Si-Yang Zheng * Penn State Milton S. Hershey Medical Center,

The Pennsylvania State University, Hershey, 17033, Pennsylvania, USA. Xin Liu, Shawn J. Rice & Chandra P. Belani * Penn State Hershey Cancer Institute, The Pennsylvania State University,

500 University Drive, Hershey, 17033, Pennsylvania, USA. Xin Liu, Shawn J. Rice & Chandra P. Belani * The Huck Institutes of the Life Sciences, The Pennsylvania State University,

University Park, 16802, Pennsylvania, USA. Merisa Nisic, Istvan Albert & Si-Yang Zheng * The Second Hospital of Nanjing, Affiliated to Medical School of Southeast University, Nanjing,

210003, China. Chuan-Dong Zhu * Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, 16802, Pennsylvania, USA. Aswathy Sebastian & Istvan

Albert * Department of Electrical Engineering, The Pennsylvania State University, University Park, 16802, Pennsylvania, USA. Si-Yang Zheng Authors * Yuan Wan View author publications You

can also search for this author inPubMed Google Scholar * Gong Cheng View author publications You can also search for this author inPubMed Google Scholar * Xin Liu View author publications

You can also search for this author inPubMed Google Scholar * Si-Jie Hao View author publications You can also search for this author inPubMed Google Scholar * Merisa Nisic View author

publications You can also search for this author inPubMed Google Scholar * Chuan-Dong Zhu View author publications You can also search for this author inPubMed Google Scholar * Yi-Qiu Xia

View author publications You can also search for this author inPubMed Google Scholar * Wen-Qing Li View author publications You can also search for this author inPubMed Google Scholar *

Zhi-Gang Wang View author publications You can also search for this author inPubMed Google Scholar * Wen-Long Zhang View author publications You can also search for this author inPubMed 

Google Scholar * Shawn J. Rice View author publications You can also search for this author inPubMed Google Scholar * Aswathy Sebastian View author publications You can also search for this

author inPubMed Google Scholar * Istvan Albert View author publications You can also search for this author inPubMed Google Scholar * Chandra P. Belani View author publications You can also

search for this author inPubMed Google Scholar * Si-Yang Zheng View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Y.W. and S.-Y.Z. designed

the research. Y.W. conducted experiments and analysed data. G.C. prepared the MMPs, assisted with peptide-sample preparation and performed proteomic analyses. S.-J.H. assisted with the

preparation of NGS samples, the analysis of RNA NGS data, and the fluorescence imaging. M.N. prepared blood plasma. C.-D.Z. and W.-Q.L. assisted with the cell culture, nEV collection and gel

electrophoresis. Y.-Q.X. performed the wound-healing assay. Z.-G.W. performed the electron microscopy. W.-L.Z. assisted with the image processing. A.S and I.A analysed NGS DNA data. X.L.,

S.J.R. and C.P.B. recruited patients and provided blood samples, tissue NGS data and clinical support. Y.W. and S.-Y.Z. wrote the manuscript. CORRESPONDING AUTHOR Correspondence to Si-Yang

Zheng. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION Supplementary tables, figures and

references (PDF 7817 kb) SUPPLEMENTARY DATASET 1 Top-1,000 expressed mRNAs (XLSX 47 kb) SUPPLEMENTARY DATASET 2 Top-1,000 expressed miRNAs (XLSX 43 kb) SUPPLEMENTARY DATASET 3 Cargo proteins

in the nanoscale extracellular vesicles (XLSX 384 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Wan, Y., Cheng, G., Liu, X. _et al._ Rapid

magnetic isolation of extracellular vesicles via lipid-based nanoprobes. _Nat Biomed Eng_ 1, 0058 (2017). https://doi.org/10.1038/s41551-017-0058 Download citation * Received: 30 April 2016

* Accepted: 07 March 2017 * Published: 10 April 2017 * DOI: https://doi.org/10.1038/s41551-017-0058 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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