Letter | Published:

Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor

Nature Biotechnology volume 32, pages 490495 (2014) | Download Citation

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Abstract

Exosomes show potential for cancer diagnostics because they transport molecular contents of the cells from which they originate. Detection and molecular profiling of exosomes is technically challenging and often requires extensive sample purification and labeling. Here we describe a label-free, high-throughput approach for quantitative analysis of exosomes. Our nano-plasmonic exosome (nPLEX) assay is based on transmission surface plasmon resonance through periodic nanohole arrays. Each array is functionalized with antibodies to enable profiling of exosome surface proteins and proteins present in exosome lysates. We show that this approach offers improved sensitivity over previous methods, enables portable operation when integrated with miniaturized optics and allows retrieval of exosomes for further study. Using nPLEX to analyze ascites samples from ovarian cancer patients, we find that exosomes derived from ovarian cancer cells can be identified by their expression of CD24 and EpCAM, suggesting the potential of exosomes for diagnostics.

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Acknowledgements

The authors thank S. Skates (Massachusetts General Hospital) for helpful discussion on statistical analyses; M. Birrer for facilitating sample collection; K. Joyes for reviewing the manuscript. This work was supported in part by US National Institutes of Health (NIH) grants R01-HL113156 (H.L.), R01-EB010011 (R.W.), R01-EB00462605A1 (R.W.), T32CA79443 (R.W.), K12CA087723-11A1 (C.M.C) and National Heart, Lung, and Blood Institute contract HHSN268201000044C (R.W.). The device was fabricated using the facilities at the Center for Nanoscale Systems (CNS) at Harvard University (National Science Foundation award ECS-0335765).

Author information

Author notes

    • Hyungsoon Im
    •  & Huilin Shao

    These authors contributed equally to this work.

Affiliations

  1. Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Hyungsoon Im
    • , Huilin Shao
    • , Yong Il Park
    • , Vanessa M Peterson
    • , Cesar M Castro
    • , Ralph Weissleder
    •  & Hakho Lee
  2. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.

    • Ralph Weissleder

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Contributions

H.I., H.S., R.W. and H.L. designed the research. C.M.C. and R.W. designed the clinical study. H.I., H.S., Y.I.P., V.M.P. and C.M.C. performed the research. V.M.P. and C.M.C. collected the clinical samples. H.I., H.S., R.W. and H.L. analyzed data. H.I., H.S., C.M.C., R.W. and H.L. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Ralph Weissleder or Hakho Lee.

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DOI

https://doi.org/10.1038/nbt.2886

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