Exploiting electrostatic shielding-effect of metal nanoparticles to recognize uncharged small molecule affinity with label-free graphene electronic biosensor

Label-free electronic biosensors as the non-electrochemical analytical tools without requirement of sophisticated instrumentation have become attractive, although their application in competitive affinity sensing of uncharged small molecules is still hindered by a difficulty in the development of competing analogues. To break through this bottleneck, we report a novel analogue made by epitope-modified metal nanoparticles to enable the electronic signaling of small-molecule analyte recognition via competitive affinity. While the electronic signaling capability of metal nanoparticle analogues is demonstrated by a graphene field-effect transistor bioassay of small-molecule glucose as a proof-of-principle, interestingly, we discover a new electronic signaling mechanism in the metal nanoparticle affinity, different to the intuitive charge accumulation expectation. On the basis of Kelvin-probe force microscopic potential characterization and theoretical discussion, we fundamentally elucidated the signaling mechanism as a seldom used electrostatic shielding-effect, that is, in the analogue-receptor affinity, metal nanoparticles with the charge density lower than receptor biomolecules can reduce the collective electrical potential via charge dispersion. Further consider the convenient epitope-modifiability of metal nanoparticles, the easy-to-develop analogues for diverse target analyte might potentially be predictable in the future. And the application of label-free electronic biosensors for the competitive affinity bioassay of range extended small molecules may thus be promoted based on the electrostatic shielding-effect.