Target-Triggered DNA Hydrogel Gating with Nanoconfinement Effect in Micropipettes for Antibiotic Resistance Gene Detection

A novel biosensing platform integrating molecular gating mechanisms with confined-space amplification is presented for ultrasensitive nucleic acid detection. The platform employs a target-triggered clamped hybridization chain reaction (C-HCR) to form DNA hydrogel networks in gold-modified glass micropipettes, creating nanoconfined spaces. Notably, this configuration demonstrates effective ion gating with enhanced sensitivity through the nanoconfinement effect as the modulation of ion current rectification signals is significantly amplified. Moreover, the DNA hydrogel can be regenerated through thermal treatment, endowing the device with good recoverability. The biosensing performance was validated by using different antibiotic resistance genes as model targets. The results showed high specificity and limits of detection down to the subnanomolar levels. The confined environment enables sensitive detection using small sample volumes of only 4 μL. The strategy of leveraging the nanoconfinement effect to amplify signal transduction may provide inspiration for the rational design of other high-performance biosensors, potentially holding great promise for disease diagnostics and environmental monitoring.