The detection of chemical and biological species is critical for applications in healthcare, environmental monitoring, food safety and drug screening. Potentiometric biochemical sensors rely on the specific adsorption of charged analytes that changes the potential of the functionalized sensor surface. The change in surface potential can be measured using a field-effect-transistor (FET) enabling low-cost fabrication, and easy integration with portable readout electronics. The FET concept has previously been applied to numerous (nano-) materials including conventional silicon, nanowires and 2D materials such as graphene. Although many biosensing experiments have been reported, many of the results are not well understood and several key challenges are still limiting their widespread application. In this work, the experimental response from a variety of sensor surfaces and transducers and will be presented.

The results show that the choice of the active interface in contact with the electrolyte determines the sensor response and selectivity (the signal) is relatively independent of the transducer. Ideally, protein recognition mechanisms are leveraged to allow only target proteins to attach to the surface, imparting signal selectivity. However, unwanted protein interactions with sensor surfaces cause signal instability and increase false-positive rates. Although commonly used to functionalize the sensing surface, carboxyl-terminated thiol self-assembled monolayers (COOH-SAMs) can have large defect densities, which in turn leads to large non-selective adsorption of proteins to hydrophobic surfaces exposed by these defects. A procedure is developed where the surface of COOH-SAMs is treated before functionalization to improve the reliability and quality of receptor attachment to the sensor surface. Beyond SAM-based sensors, there has been significant interest in biomedical applications of two-dimensional materials such as graphene, including potentiometric sensing. There is conflicting literature on to what extent interaction from the substrate are transmitted through a monolayer, and the subsequent effect on biomolecule interactions are unknown. Therefore, the degree to which the substrate influences graphene-protein interactions is explored. Finally, the choice of the readout transducer (e.g. a graphene transistor) is shown to influence the noise limit, and, hence, the signal-to-noise ratio. Models for diffusion, attachment, and electrical response of these sensors will be described that demonstrates good agreement to experimental data. Despite the current challenges facing label-free, portable biosensors, the work presented here provides a step towards reliable biosensing.