Engineering graphene oxide interfaces for electrochemical biosensing of biomolecules, cells, and organoids

Graphene oxide (GO) has established itself as a premier material for electrochemical biosensing due to its exceptional chemical tunability, aqueous processability, and unique sp²-sp³ hybridized structure. This review provides a comprehensive analysis of diverse engineering strategies to functionalize GO, enabling highly sensitive and selective detection of a broad spectrum of biological analytes. We systematically categorize these advancements into five key methodologies: (1) controlled reduction to precisely tune electrical conductivity and surface defects, (2) covalent functionalization for robust bioreceptor immobilization, (3) non-covalent modification to preserve biomolecular conformation, (4) metal nanoparticle hybridization for enhanced electrocatalysis, and (5) integration with polymeric/framework materials to build advanced three-dimensional sensing architectures. By examining applications ranging from small molecule metabolites and proteins to nucleic acids and whole pathogens, we demonstrate how tailored GO interfaces overcome conventional sensing trade-offs. Finally, we highlight the pivotal role of these engineered GO platforms in addressing the challenges of real-time monitoring at complex biological interfaces, including living cells and organoids, and outline the pathway toward clinically deployable diagnostic technologies.