Two-dimensional-material-based FET biosensors have gained attention for being label-free and having ultra-sensitive detection capability. The high carrier mobility and large surface-to-volume ratio of 2D materials enable low detection limits under buffer conditions; however, practical detection still faces many challenges. Current reviews have largely summarized materials, functionalization routes, or target classes separately, but a clearer framework linking interface design, device architecture, and practical sensing performance is still needed. In this review, we examine how interfacial engineering and device architecture govern signal transduction and sensing behavior in 2D material FET biosensors. We also analyze the major barriers to real-sample detection, including Debye screening, nonspecific adsorption, and signal drift, together with commonly used mitigation strategies. On this basis, an “interface–device–performance” framework is discussed as a conceptual approach for understanding the relationship between molecular recognition, electrical response, and sensing performance. This review mainly focuses on the key challenges of 2D material FET biosensors in practical medical applications, discusses the differences between material and application perspectives, and examines the major factors limiting clinical translation.
Gao et al. (Sat,) studied this question.