Spatially Controlled DNA Hydrogel–MXCT Nanofluidic Biosensor for Noninvasive Iontronic Detection of Estradiol across the Menstrual Cycle

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_<i>x</i> 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.