Tissue-adhesive hydrogel–MXene biosensor for in situ intraoral TNF-α detection

Current dental care relies on subjective assessments or sophisticated diagnostics, both struggling to balance efficiency and accuracy. In situ biosensors offer a promising solution for real-time biomarker detection, yet their practical deployment in oral tissue is hindered by challenges in sensitivity, specificity, and stability due to low biomarker concentrations, molecular-level heterogeneity, and dynamic intraoral interactions. Here, we develop a tissue-adhesive hydrogel-MXene (TAHM) biosensor, integrating a graphene/MXene sensing probe, a tissue-adhesive patch, and a selective-permeable hydrogel membrane, for in situ detection of tumor necrosis factor-α, a proinflammatory cytokine. Our TAHM biosensor achieves high sensitivity with a limit of detection of 18.2 femtograms per milliliter, excellent selectivity with an interference coefficient below 7%, and mechanical stability with resistance variation under 0.5% under varying stretch ratio and loading rates. The sensor's performance is further validated through in vitro, in vivo, and ex vivo experiments. The work highlights the potential of in situ biosensor as a transformative tool for real-time oral diagnostics.