Engineering Graphene Field-Effect Transistor Biosensors for Disease Biomarkers Detection in Liquid Biopsy

Electrical biosensors based on graphene field-effect transistors (GFETs) have shown great potential for the rapid and highly sensitive detection of a wide range of biomolecules. They are biocompatible, easy to functionalize, and scalable for mass production and can be incorporated into portable devices for point-of-care diagnostics. This review comprehensively examines the transition of GFET biosensors from laboratory research to real-world clinical applications. It begins with an overview of the versatility of the GFETs platform for biomarkers detection. Subsequently, it explores a variety of biofunctionalization strategies, including covalent and noncovalent biofunctionalization, and their impact on biosensor performance. This review addresses the critical challenges related to the performance limitations of GFETs in clinical settings including sensitivity, selectivity, and stability. We discuss strategies for enhancing the sensitivity and selectivity of the detection of biomarkers in complex liquid biopsies or physiological conditions, including strategies to overcome Debye screening effects and nonspecific binding effects and improve signal amplification. Furthermore, this review addresses factors such as device noise, its impact on sensitivity, and methods to minimize noise levels. Additionally, it explores the significance of multiplexed detection for improving the diagnostic accuracy and efficiency. Crucial aspects of device integration, including the development of portable readout systems, are discussed. It summarizes recent advancements in the field, highlighting studies that have successfully integrated GFETs with portable electronics for disease detection. These efforts, often utilizing foundry-manufactured GFETs, demonstrate the feasibility of creating compact and user-friendly devices suitable for point-of-care applications. The review summarizes recent studies that have successfully employed GFET biosensors to detect different disease biomarkers in complex mediums. Finally, we outline the future development of GFET-based sensing systems required to transition this technology from laboratory to clinical applications.