Spatially Controlled DNA Hydrogel-MXCT Nanofluidic Biosensor for Noninvasive Iontronic Detection of Estradiol across...

Accurate monitoring of estradiol (E2) is crucial for assessing reproductive health, managing fertility, and diagnosing endocrine disorders. We report a noninvasive iontronic biosensor based on a DNA hydrogel-functionalized MXene/Cu-TCPP (MXCT) nanofluidic membrane for ultrasensitive salivary E2 detection. The MXCT laminate, formed by alternating Ti₃C₂T_x MXene and Cu-TCPP nanosheets, provides a mechanically robust, conductive, and ion-selective 2D framework. Within these confined nanochannels, aptamer-triggered DNA hydrogel assembly produces volumetric steric modulation, enabling three-dimensional spatial control of ion transport beyond conventional surface regulation. This synergistic hydrogel-nanofluidic coupling yields femtomolar sensitivity, a detection range of 50 fM-500 pM, and a detection limit of 28 fM, with excellent selectivity and reproducibility. The platform enables salivary E2 profiling across menstrual cycles, accurately capturing physiological hormonal dynamics. This work establishes a robust strategy for hydrogel-gated nanofluidic iontronics, offering a promising route toward low-cost, portable hormone diagnostics and broader molecular sensing applications.