Sensitive multiplex detection of serological liver cancer biomarkers using SERS-active photonic crystal fiber probe

J Biophotonics. 2014 Nov;7(11-12):956-65. doi: 10.1002/jbio.201300084. Epub 2013 Aug 21.

Abstract

Surface-enhanced Raman scattering (SERS) spectroscopy possesses the most promising advantage of multiplex detection for biosensing applications, which is achieved due to the narrow 'fingerprint' Raman spectra from the analyte molecules. We developed an ultrasensitive platform for the multiplex detection of cancer biomarkers by combining the SERS technique with a hollow-core photonic crystal fiber (HCPCF). Axially aligned air channels inside the HCPCF provide an excellent platform for optical sensing using SERS. In addition to the flexibility of optical fibers, HCPCF provides better light confinement and a larger interaction length for the guided light and the analyte, resulting in an improvement in sensitivity to detect low concentrations of bioanalytes in extremely low sample volumes. Herein, for the first time, we demonstrate the sensitive multiplex detection of biomarkers immobilized inside the HCPCF using antibody-conjugated SERS-active nanoparticles (SERS nanotags). As a proof-of-concept for targeted multiplex detection, initially we carried out the sensing of epidermal growth factor receptor (EGFR) biomarker in oral squamous carcinoma cell lysate using three different SERS nanotags. Subsequently, we also achieved simultaneous detection of hepatocellular carcinoma (HCC) biomarkers-alpha fetoprotein (AFP) and alpha-1-antitrypsin (A1AT) secreted in the supernatant from Hep3b cancer cell line. Using a SERS-HCPCF sensing platform, we could successfully demonstrate the multiplex detection in an extremely low sample volume of ∼20 nL. In future, this study may lead to sensitive biosensing platform for the low concentration detection of biomarkers in an extremely low sample volume of body fluids to achieve early diagnosis of multiple diseases. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

Keywords: SERS nanotag; Surface-enhanced Raman scattering; hepatocellular carcinoma; multiplex detection; photonic crystal fiber.

MeSH terms

  • Biomarkers, Tumor / chemistry*
  • Biosensing Techniques
  • Body Fluids
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line, Tumor
  • Crystallization
  • ErbB Receptors / metabolism
  • Humans
  • Lasers
  • Light
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / metabolism
  • Microscopy, Electron, Transmission / methods
  • Nanoparticles / chemistry
  • Nanotechnology / methods
  • Optics and Photonics
  • Spectrum Analysis, Raman / methods
  • Surface Properties
  • alpha 1-Antitrypsin / metabolism
  • alpha-Fetoproteins / metabolism

Substances

  • Biomarkers, Tumor
  • alpha 1-Antitrypsin
  • alpha-Fetoproteins
  • ErbB Receptors