From surface to signal: Clinical pathways for transition metal dichalcogenide-based electrochemical biosensors

Electrochemical biosensors enable rapid, low-cost, and portable clinical diagnostics. While graphene has demonstrated ultrasensitive detection, its clinical translation is constrained by reproducibility issues, unstable surface chemistry, and complex fabrication processes. Transition metal dichalcogenides (TMDs) have emerged as promising next-generation materials due to their tunable electronic structures, abundant catalytic active sites, and intrinsic suitability for biofunctionalization, enabling enhanced analytical sensitivity. Despite these advances, their clinical deployment remains limited by material instability, interfacial resistance, signal interference, and insufficient validation in real biological matrices. This review applies a five-axis evaluation framework-analytical performance, operational stability, manufacturability, biointerface compatibility, and system readiness-to systematically assess TMD-based electrochemical biosensors, with a particular focus on MoS₂-dominated platforms. We critically examine material properties, device engineering, and key translational gaps, particularly in matrix validation and scalable manufacturing. Furthermore, we propose a gated technology readiness roadmap aligned with regulatory standards to accelerate clinical translation and facilitate the adoption of TMD-based biosensing technologies.