Unlocking the Potential of MXene‐Based Electrochemical Biosensors: A Review of Biofunctionalization Strategies and Biosensing Principles

ABSTRACT Electrochemical biosensors enable the accurate and timely detection of clinical biomarkers, improving healthcare and precision medicine. MXene nanosheets, a class of 2D transition metal carbides, nitrides, and carbonitrides, are promising materials for developing next‐generation electrochemical biosensors due to their unique physicochemical properties, including high electrical conductivity, a large specific surface area, and an abundance of surface terminal groups, rendering them hydrophilic and well‐suited for the surface immobilization of biorecognition elements and their transduction of into analytical signals. This review highlights the recent progress in MXene‐based electrochemical biosensors for clinical biomarker detection, focusing on their biofunctionalization approaches (including covalent and non‐covalent approaches, as well as hybrid materials) and electrochemical biosensing strategies based on biomarker type (proteins, nucleic acids, metabolites, cells, and extracellular vesicles). We discuss factors affecting their sensitivity, selectivity, and dynamic range, highlighting how material design can be leveraged to optimize biosensor functions. Moreover, we provide a forward‐thinking perspective on the challenges that hinder the translation of MXene‐based biosensors into clinical practice. We emphasize the importance of developing stable and bio‐orthogonal biofunctionalization strategies, as well as multiplexed biosensing strategies, to achieve meaningful applications of MXenes in the clinical practice based on the ultrasensitive detection of clinically relevant biomarkers.