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

Nat Commun. 2018 Jan 12;9(1):175. doi: 10.1038/s41467-017-02261-1.

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Brain Neoplasms / chemistry
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Extracellular Vesicles / chemistry*
  • Extracellular Vesicles / metabolism
  • Glioblastoma / chemistry
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Humans
  • Microfluidics / instrumentation
  • Microfluidics / methods*
  • RNA / genetics
  • RNA / metabolism

Substances

  • epidermal growth factor receptor VIII
  • RNA
  • ErbB Receptors