New Paradigm of Label-Free Biosensor Enabled by Two-Dimensional Hexagonal Titanium Oxide

Biosensors with high sensitivity and selectivity are increasingly in demand, especially in the fields of medical devices, health monitoring, and treatment, etc. Two-dimensional (2D) materials-enabled nanotechnology has brought promising pathways in rapid, highly sensitive, and selective cancer biomarker sensors. The recently developed 2D planar hexagonal titanium oxide (h-TiO₂) monolayer derived from the metal-gas interface exhibited a unique narrowed bandgap and extraordinary carrier transport performance up to 950 cm² V⁻¹s⁻¹ at room temperature, compared to that of conventional bulk phased ones. The findings show exciting opportunities in realizing high-performance electronic biosensors.<br/>Herein, we demonstrated the sensing capability of 2D h-TiO₂ by FET-based biosensor for carcinoembryonic antigen (CEA) detection-a representative broad-spectrum tumor marker. The h-TiO₂ nanosheets FET devices were functionalized with monoclonal CEA antibody using the probe linker of 3-aminopropyltriethoxysilane. The dissociation constant between anti-CEA and CEA protein was estimated to be approximately 1.03 × 10^-10 M by hill model, showing high affinity between CEA protein and anti-CEA. Multiple techniques including XPS, and KPFM were carried out to investigate the surface condition at each of the functionalization stages. The real-time measurement of 2D h-TiO₂ FET biosensor showed a high specificity of and an ultralow limit of detection (LOD) down to 0.23 pg ml^-1, exceeding the performance enabled by conventional 2D systems including graphene, black phosphorus (BP), transition metal dichalcogenides (TMDs), etc. The outcome of this work demonstrates the significant potential of 2D hexagonal metal oxide in biological sensing applications.