Redox Buffering Effects in Potentiometric Detection of DNA Using Thiol-Modified Gold Electrodes

[Image: see text] Label-free potentiometric detection of DNA molecules using a field-effect transistor (FET) with a gold gate offers an electrical sensing platform for rapid, straightforward, and inexpensive analyses of nucleic acid samples. To induce DNA hybridization on the FET sensor surface to enable potentiometric detection, probe DNA that is complementary to the target DNA has to be immobilized on the FET gate surface. A common method for probe DNA functionalization is based on thiol–gold chemistry, immobilizing thiol-modified probe DNA on a gold gate with thiol–gold bonds. A self-assembled monolayer (SAM), based on the same thiol–gold chemistry, is also needed to passivate the rest of the gold gate surface to prevent non-specific adsorption and to enable favorable steric configuration of the probe DNA. Herein, the applicability of such FET-based potentiometric DNA sensing was carefully investigated, using a silicon nanoribbon FET with a gold-sensing gate modified with thiol–gold chemistry. We discover that the potential of the gold-sensing electrode is determined by the mixed potential of the gold–thiol and gold–oxygen redox interactions. This mixed potential gives rise to a redox buffer effect which buffers the change in the surface charge induced by the DNA hybridization, thus suppressing the potentiometric signal. Analogous redox buffer effects may also be present for other types of potentiometric detections of biomarkers based on thiol–gold chemistry.