Chemically functionalised graphene FET biosensor for the label-free sensing of exosomes

Abstract

A graphene field-effect transistor (gFET) was non-covalently functionalised with 1-pyrenebutyric acid N-hydroxysuccinimide ester and conjugated with anti-CD63 antibodiesfor the label-free detection of exosomes.Using a microfluidic channel, part of a graphene film was exposed to solution. The change in electrical properties of the exposed graphene created anadditional minimum alongside the original Dirac point inthe drain-source current(Ids)-back-gate voltage (Vg) curve. When phosphate buffered saline (PBS) was present in the channel, the additional minimum was present at a Vglower than the original Dirac point and shifted with time when exosomes were introduced into the channel.Thisshift of the minimum from the PBS reference point reached saturationafter 30 minutesand was observed for multiple exosome concentrations. Upon conjugation with an isotype control, sensor responsetothe highest concentration ofexosomes was negligible in comparison to that with anti-CD63antibody, indicatingthat thefunctionalised gFETcan specifically detect exosomes at least down to 0.1μg/mLand is sensitive to concentration. Such a gFET biosensor has not been used before for exosome sensing and could be an effective tool for the liquid-biopsy detection of exosomes as biomarkers for early-stage identification of diseases such as cancer.