Graphene Oxide Signal Reporter Based Multifunctional Immunosensing Platform for Amperometric Profiling of Multiple Cytokines in Serum

ACS Sens. 2018 Aug 24;3(8):1553-1561. doi: 10.1021/acssensors.8b00365. Epub 2018 Aug 1.

Abstract

Cytokines are small proteins and form complicated cytokine networks to report the status of our health. Thus, accurate profiling and sensitive quantification of multiple cytokines is essential to have a comprehensive and accurate understanding of the complex physiological and pathological conditions in the body. In this study, we demonstrated a robust electrochemical immunosensor for the simultaneous detection of three cytokines IL-6, IL-1β, and TNF-α. First, graphene oxides (GO) were loaded with redox probes nile blue (NB), methyl blue (MB), and ferrocene (Fc), followed by covalent attachment of anti-cytokine antibodies for IL-6, IL-1β, and TNF-α, respectively, to obtain Ab2-GO-NB, Ab2-GO-MB, and Ab2-GO-Fc, acting as the signal reporters. The sensing interface was fabricated by attachment of mixed layers of 4-carboxylic phenyl and 4-aminophenyl phosphorylcholine (PPC) to glassy carbon surfaces. After that, the capture monoclonal antibody for IL-6, IL-1β, and TNF-α was modified to the carboxylic acid terminated sensing interface. And finally a sandwich assay was developed. The quantitative detection of three cytokines was achieved by observing the change in electrochemical signal from signal reporters Ab2-GO-NB, Ab2-GO-MB, and Ab2-GO-Fc. The designed system has been successfully used for detection of three cytokines (IL-6, IL-1β, and TNF-α) simultaneously with desirable performance in sensitivity, selectivity, and stability, and recovery of 93.6%-105.5% was achieved for determining cytokines spiked in the whole mouse serum.

Keywords: cytokines; electrochemistry; graphene oxides; immunosensors; multiplex detection; redox probes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Benzenesulfonates / chemistry
  • Biosensing Techniques / methods*
  • Cytokines / blood*
  • Cytokines / immunology
  • Electrochemical Techniques*
  • Electrodes
  • Ferrous Compounds / chemistry
  • Graphite / chemistry*
  • Immunoassay*
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Limit of Detection
  • Metallocenes / chemistry
  • Mice
  • Oxazines / chemistry
  • Oxidation-Reduction
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies
  • Benzenesulfonates
  • Cytokines
  • Ferrous Compounds
  • Interleukin-6
  • Metallocenes
  • Oxazines
  • Tumor Necrosis Factor-alpha
  • graphene oxide
  • Nile Blue
  • Graphite
  • Methyl Blue
  • ferrocene