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Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles

Author

Listed:
  • Eduardo Reátegui

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Kristan E. Vos

    (Harvard Medical School
    Netherlands Cancer Institute)

  • Charles P. Lai

    (Harvard Medical School
    Academia Sinica)

  • Mahnaz Zeinali

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Nadia A. Atai

    (Harvard Medical School)

  • Berent Aldikacti

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Frederick P. Floyd

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Aimal Khankhel

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Vishal Thapar

    (Harvard Medical School)

  • Fred H. Hochberg

    (University of California San Diego)

  • Lecia V. Sequist

    (Harvard Medical School
    Harvard Medical School)

  • Brian V. Nahed

    (Harvard Medical School
    Harvard Medical School)

  • Bob Carter

    (University of California San Diego)

  • Mehmet Toner

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Leonora Balaj

    (Harvard Medical School)

  • David Ting

    (Harvard Medical School)

  • Xandra O. Breakefield

    (Harvard Medical School
    Harvard Medical School)

  • Shannon L. Stott

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

Abstract

Extracellular vesicles (EVs) carry RNA, DNA, proteins, and lipids. Specifically, tumor-derived EVs have the potential to be utilized as disease-specific biomarkers. However, a lack of methods to isolate tumor-specific EVs has limited their use in clinical settings. Here we report a sensitive analytical microfluidic platform (EVHB-Chip) that enables tumor-specific EV-RNA isolation within 3 h. Using the EVHB-Chip, we achieve 94% tumor-EV specificity, a limit of detection of 100 EVs per μL, and a 10-fold increase in tumor RNA enrichment in comparison to other methods. Our approach allows for the subsequent release of captured tumor EVs, enabling downstream characterization and functional studies. Processing serum and plasma samples from glioblastoma multiforme (GBM) patients, we can detect the mutant EGFRvIII mRNA. Moreover, using next-generation RNA sequencing, we identify genes specific to GBM as well as transcripts that are hallmarks for the four genetic subtypes of the disease.

Suggested Citation

  • Eduardo Reátegui & Kristan E. Vos & Charles P. Lai & Mahnaz Zeinali & Nadia A. Atai & Berent Aldikacti & Frederick P. Floyd & Aimal Khankhel & Vishal Thapar & Fred H. Hochberg & Lecia V. Sequist & Bri, 2018. "Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02261-1
    DOI: 10.1038/s41467-017-02261-1
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