Probe density optimization through gold Nano-islands population regulation for improved sensitivity of aptamer-functionalized MoS₂-FET biosensors

Achieving higher sensitivity is always paramount for the detection of biomolecules in medical applications. Significant efforts have been made to improve the sensitivity of aptamer-functionalized two-dimensional material-based field-effect transistor (A-2DFET) biosensors, typically by increasing the probe density. However, the underlying mechanism by which the probe density affects the sensitivity remains unclear, and a rigorous mathematical model incorporating the probe density is also lacking. In this work, we develop a probe density-incorporated mathematical model of MoS₂-based A-2DFET biosensors. Analysis of this model reveals an optimal density-which is influenced by the spatial structure, charges of the probe-target complexes, and the binding affinity-is expected to achieve the highest sensitivity. To validate the model, we regulate the probe density by controlling the population of gold Nano-islands (AuNIs), which function as aptamer anchoring sites, before investigating the sensitivity of different devices. Detection experiments targeting interferon-gamma (IFN-γ) demonstrate that the sensitivity trend across different probe densities, initially increasing and then decreasing as the probe density rises, is consistent with the prediction of the model. By elucidating the mechanistic role of probe density in determining the sensitivity, this study provides an important theoretical basis for the design and application of A-2DFET biosensors.