Bioinspired Hydrogel-Functionalized Microchannel-Gated Junction Field-Effect Transistor for Highly Sensitive Glutathione Detection

Inspired by the gating behavior of biological ion channels, microchannel-based sensing has emerged as an effective strategy for regulating ionic transport through charge density and pore size modulation. Field-effect transistor (FET)-based biosensors have received considerable attention owing to their high sensitivity to subtle charge variations. In this study, this character had been coupled with the junction field-effect transistor (JFET) detection technique to develop a sensitive biosensor for glutathione (GSH). A hydrogel was formed by Schiff-base crosslinking between aldehyde-modified hyaluronic acid (AHA) and 3-[(3-hydrazinyl-3-oxopropyl)disulfanyl] propanehydrazide (DTP) and subsequently confined within the microchannel, which served as a tunable resistor positioned between the gate and source of the JFET. Variations in the microchannel resistance induce a voltage division effect, thereby modulating the distribution of the effective gate voltage, which changes the channel current. Upon the presence of GSH, disulfide bonds of DTP within the hydrogel were reduced, generating thiol groups and disrupting the hydrogel network, which enlarged the pore size and increased the negative charge density. These changes reduced the microchannel resistance and increased the effective negative gate voltage, leading to a significant reduction of the channel current. The biosensor exhibited excellent sensitivity and selectivity toward GSH with a linear range from 100 nM to 1.00 mM, and the detection limit was 38.1 nM, along with good recovery and reproducibility in diluted human serum samples. This sensor provides a novel strategy for highly sensitive GSH detection and holds potential as a versatile platform for clinical diagnostics and disease monitoring.