Exploiting the Anti-Aggregation of Gold Nanostars for Rapid Detection of Hand, Foot, and Mouth Disease Causing Enterovirus 71 Using Surface-Enhanced Raman Spectroscopy

Anal Chem. 2017 May 16;89(10):5373-5381. doi: 10.1021/acs.analchem.7b00066. Epub 2017 Apr 26.

Abstract

Enterovirus 71 (EV71) is a major public health threat that requires rapid point-of-care detection. Here, we developed a surface-enhanced Raman spectroscopy (SERS)-based scheme that utilized protein-induced aggregation of colloidal gold nanostars (AuNS) to rapidly detect EV71 without the need for fabricating a solid substrate, Raman labels or complicated sample handling. We used AuNS (hydrodynamic diameter, DH of 105.12 ± 1.13 nm) conjugated to recombinant scavenger receptor class B, member 2 (SCARB2) protein with known affinity to EV71. In the absence of EV71, AuNS-SCARB2 aggregated in biological media and produced four enhanced Raman peaks at 390, 510, 670, and 910 cm-1. In the presence of EV71, the three peaks at 510, 670, and 910 cm-1 disappeared, while the peak at 390 cm-1 diminished in intensity as the virus bound to AuNS-SCARB2 and prevented them from aggregation. These three peaks (510, 670, and 910 cm-1) were potential markers for specific detection of EV71 as their disappearance was not observable with a different dengue virus (DENV) as our control. Furthermore, the Raman measurements from colloidal SERS were more sensitive in probing the aggregation of AuNS-SCARB2 for detecting the presence of EV71 in protein-rich samples compared to UV-vis spectrum measurements. With this facile "anti-aggregation" approach, we were able to detect EV71 in protein-rich biological medium within 15 min with reasonable sensitivity of 107 pfu/mL and minimal sample preparation, making this translatable for point-of-care applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enterovirus A, Human / chemistry
  • Enterovirus A, Human / isolation & purification*
  • Gold / chemistry
  • Hand, Foot and Mouth Disease / diagnosis*
  • Hand, Foot and Mouth Disease / virology
  • Humans
  • Lysosomal Membrane Proteins / chemistry
  • Lysosomal Membrane Proteins / genetics
  • Lysosomal Membrane Proteins / metabolism
  • Nanostructures / chemistry*
  • Protein Binding
  • Receptors, Scavenger / chemistry
  • Receptors, Scavenger / genetics
  • Receptors, Scavenger / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Spectrophotometry
  • Spectrum Analysis, Raman*

Substances

  • Lysosomal Membrane Proteins
  • Receptors, Scavenger
  • Recombinant Proteins
  • SCARB2 protein, human
  • Gold