Label-Free and Low-Power Driven Cancer Biomarker Detection Enabled by 2D Hexagonal Titanium Oxide

2D nanomaterials have shown significant advances in next-generation biosensor development. However, current 2D-enabled electronic biosensors rarely achieve a detection limit down to pico-gram level, possibly due to their intrinsic low carrier mobilities, biocompatibility or instability. TiO 2 , a biocompatible material, has been widely adopted in bio-applications. Recently, 2D TiO 2 with a unique planar hexagonal phase exhibits a reduced bandgap of 2 eV and high p-type mobility. A small perturbation could stimulate an observable electronic swing, enabling a high-performance biosensor in a label-free manner. Here, 2D h-TiO 2 is fabricated into a liquid-gated field-effect transistor, while a wide spectrum, nonspecific biomarker carcinoembryonic antigen (CEA) is selected as the target molecule. The h-TiO 2 surface is first functionalized with 3-aminopropyltriethoxysilane and subsequently decorated with anti-CEA, creating an affinity probe toward CEA molecules. The real-time response to different concentrations of CEA is tested from 1 pg mL −1 to 10 ng mL −1 under a low working voltage of 0.05 V, and an ultralow detection limit of 0.22 pg mL −1 is achieved. Meanwhile, the selectivity of the devices is demonstrated using cytokeratin-19-fragment and neuron-specific enolase. The results highlight the potential of layered hexagonal metal oxides for high-performance biosensors, enabling future low-power portable devices for disease diagnosis.