The role of graphene patterning in field-effect transistor sensors to detect the tau protein for Alzheimer's disease: Simplifying the immobilization process and improving the performance of graphene-based immunosensors

Biosens Bioelectron. 2021 Nov 15:192:113519. doi: 10.1016/j.bios.2021.113519. Epub 2021 Jul 24.

Abstract

We report the improvement in the sensing performance of electrolyte-gated graphene field-effect transistor (FET) sensors capable of detecting tau protein through a simplified, linker-free, anti-tau antibody immobilization process. For most of the graphene-based immunosensor, linkers, such as pyrenebutanoic acid, succinimidyl ester (PSE) must be used to the graphene surface, while the other side of linkers serves to capture the antibodies that can specifically interact with the target biomarker. In this study, graphene was patterned into eight different types and linker-free patterned graphene FET sensors were fabricated to verify their detection performance. The linker-free antibody immobilization to patterned graphene exhibited that the antibody was immobilized to the edge defect and had a doping-like behaviors on graphene. As the tau protein concentration in the electrolyte increased from 10 fg/ml to 1 ng/ml, the performances, charge neutral point shift and current change rate of the patterned graphene sensors without linkers were enhanced 2-3 times compared to a pristine graphene sensor with the PSE linker. Moreover, tau protein in the plasma of five Alzheimer's disease patients was measured using a linker-free patterned graphene sensor. It shows a 3-4 times higher current change rate than that of pristine graphene sensor with the PSE linker. Since the antibody is immobilized directly without a linker, a patterned graphene sensor without a linker can operate more sensitively in higher ionic concentration electrolyte.

Keywords: Antibody immobilization; Field-effect transistor sensor; Graphene patterning; Immunosensor; Linker-free; Tau protein.

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Biosensing Techniques*
  • Graphite*
  • Humans
  • Immunoassay
  • Transistors, Electronic
  • tau Proteins

Substances

  • tau Proteins
  • Graphite