Abstract
Abstract Accurate and reliable glucose sensors are crucial in effective diabetes management and preventing associated complications. Nanomaterials based on graphene and its derivatives such as reduced graphene oxide have exhibited exceptional properties for the electrochemical detection of glucose due to their outstanding electrical conductivity, large surface area, chemical stability, and ease of functionalization. This review provides a comprehensive overview of the evolution of electrochemical glucose sensors across generations, followed by an in-depth analysis of electrochemical sensing mechanisms, including the activated chemisorption model and the incipient hydrous oxide adatom mediator (IHOAM) model. This review emphasizes the integration of graphene with noble metals, transition metals, and metal oxides, which demonstrates synergistic improvements in electrocatalytic activity and operational stability. It offers a comparative analysis of various graphene synthesis methods and their impact on electrochemical performance. Furthermore, the review addresses critical challenges that continue to hinder sensor performance, including sensor fouling, biological interference, and inconsistencies in material properties. By summarizing recent advancements, this work not only provides an updated overview of the field but also highlights key research gaps that must be addressed to advance the development of graphene-based electrochemical glucose sensors. This review outlines promising future research directions, including the development of wearable and flexible sensing platforms, as well as the incorporation of artificial intelligence for improved signal processing and diagnostic accuracy. It also examines emerging strategies such as advanced surface functionalization, composite material engineering, and novel electrode architectures designed to enhance specificity, stability, and real-time sensing capabilities. Through a comprehensive analysis of the interactions between material characteristics, underlying electrochemical mechanisms, and sensor-level performance metrics, this review provides a comprehensive framework to guide the rational design and development of next-generation glucose sensing platforms with significant potential for clinical translation and commercial implementation.