Low-Noise Finite-Bandgap FET Biosensors in the Nonlinear Gouy-Chapman-Stern Region: A Universal Calibration Curve

In the realm of biosensors, FET sensors have been recognized for their immunity to electronic tunneling noise and weakly-charged protein interference in biological samples. However, signal corruption arises due to pH fluctuations and counterions present in the electrolyte bulk. In this study, researchers reveal that electrolyte noise is mitigated by the Stern layer, a phenomenon that emerges beyond the linear Debye-Huckel limit when the interfacial potential drop surpasses the thermal voltage.

By employing a fully nonlinear Gouy-Chapman-Stern (GCS) theory, a universal calibration curve has been derived. This curve effectively aligns low-noise FET signals for miRNA, extracellular vesicles (EV), and protein detection across an extensive range – spanning eleven orders of magnitude in analyte concentration. The core of the theory hinges on the dissociation constant KD and a gain parameter {chi}, which embodies the interplay between the reporter charge and the buffer's Debye screening. These parameters must exhibit sufficient magnitude to establish the low-noise GCS condition.

The limit of detection (LOD) is determined by the ratio KD/{chi}. This value can be fine-tuned by adjusting probe density, the charge reporter, and the buffer solution. In the context of miRNA detection, an optimized hybridization buffer yields a LOD of approximately 1 pM, corresponding to a {chi} value of around 22. In the case of EV detection, multivalent capture significantly diminishes the dissociation constant by four orders of magnitude relative to protein detection, leading to a {chi} value of about 34 and an LOD of roughly 10 fM.