Hybrid Nanoplasmonic Porous Biomaterial Scaffold for Liquid Biopsy Diagnostics Using Extracellular Vesicles

Tatu Rojalin, Hanna J. Koster, Juanjuan Liu, Rachel R. Mizenko, Di Tran, Sebastian Wachsmann-Hogiu, Randy P. Carney

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


For more effective early-stage cancer diagnostics, there is a need to develop sensitive and specific, non- or minimally invasive, and cost-effective methods for identifying circulating nanoscale extracellular vesicles (EVs). Here, we report the utilization of a simple plasmonic scaffold composed of a microscale biosilicate substrate embedded with silver nanoparticles for surface-enhanced Raman scattering (SERS) analysis of ovarian and endometrial cancer EVs. These substrates are rapidly and inexpensively produced without any complex equipment or lithography. We extensively characterize the substrates with electron microscopy and outline a reproducible methodology for their use in analyzing EVs from in vitro and in vivo biofluids. We report effective chemical treatments for (i) decoration of metal surfaces with cysteamine to nonspecifically pull down EVs to SERS hotspots and (ii) enzymatic cleavage of extraluminal moieties at the surface of EVs that prevent localization of complementary chemical features (lipids/proteins) to the vicinity of the metal-enhanced fields. We observe a major loss of sensitivity for ovarian and endometrial cancer following enzymatic cleavage of EVs' extraluminal domain, suggesting its critical significance for diagnostic platforms. We demonstrate that the SERS technique represents an ideal tool to assess and measure the high heterogeneity of EVs isolated from clinical samples in an inexpensive, rapid, and label-free assay.

Original languageEnglish (US)
Pages (from-to)2820-2833
Number of pages14
JournalACS Sensors
Issue number9
StatePublished - Sep 25 2020


  • biophotonics
  • cancer
  • exosomes
  • liquid biopsy
  • nanomaterials
  • Raman spectroscopy
  • SERS

ASJC Scopus subject areas

  • Bioengineering
  • Instrumentation
  • Process Chemistry and Technology
  • Fluid Flow and Transfer Processes


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