Wafer-scale high-resolution patterning of reduced graphene oxide films for detection of low concentration biomarkers in plasma

Sci Rep. 2016 Aug 10:6:31276. doi: 10.1038/srep31276.

Abstract

Given that reduced graphene oxide (rGO)-based biosensors allow disposable and repeatable biomarker detection at the point of care, we developed a wafer-scale rGO patterning method with mass productivity, uniformity, and high resolution by conventional micro-electro-mechanical systems (MEMS) techniques. Various rGO patterns were demonstrated with dimensions ranging from 5 μm up to several hundred μm. Manufacture of these patterns was accomplished through the optimization of dry etching conditions. The axis-homogeneity and uniformity were also measured to verify the uniform patternability in 4-inch wafer with dry etching. Over 66.2% of uniform rGO patterns, which have deviation of resistance within range of ±10%, formed the entire wafer. We selected amyloid beta (Aβ) peptides in the plasma of APP/PS1 transgenic mice as a study model and measured the peptide level by resistance changes of highly uniform rGO biosensor arrays. Aβ is a pathological hallmark of Alzheimer's disease and its plasma concentration is in the pg mL(-1) range. The sensor detected the Aβ peptides with ultra-high sensitivity; the LOD was at levels as low as 100 fg mL(-1). Our results provide biological evidences that this wafer-scale high-resolution patterning method can be used in rGO-based electrical diagnostic devices for detection of low-level protein biomarkers in biofluids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / blood
  • Amyloid beta-Peptides
  • Animals
  • Biomarkers / blood*
  • Biosensing Techniques
  • Disease Models, Animal
  • Electrochemical Techniques / instrumentation
  • Equipment Design
  • Graphite / chemistry*
  • Limit of Detection
  • Male
  • Materials Testing
  • Mice
  • Mice, Transgenic
  • Micro-Electrical-Mechanical Systems
  • Oxides / chemistry*
  • Permeability
  • Plasma / chemistry*
  • Sensitivity and Specificity

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Oxides
  • Graphite