MXene-based biosensors for hospital-on-chip diagnostics: a coordination chemistry framework from materials design to clinical translation

MXenes, a rapidly expanding family of two-dimensional transition metal carbides and nitrides, have emerged as promising materials for hospital-on-chip (HoC) diagnostics because of their high electrical conductivity, chemically tunable surfaces, and versatile biofunctionalization. Despite substantial advances in device performance, the molecular origins of signal generation, selectivity, and long-term stability remain poorly defined. This review establishes coordination chemistry as a mechanistic framework for interpreting MXene-based biosensing, highlighting how metal–ligand interactions at the biointerface can govern the analytical performance alongside intrinsic electronic conductivity. Ligand-field effects, hard–soft acid–base (HSAB) principles, redox-active coordination environments, and coordination-mediated charge transfer were examined in relation to biomolecular recognition, interfacial electron transfer, and signal transduction. Particular emphasis is placed on the influence of surface terminations (–O, –OH, –F, and –Cl), defect-associated metal sites, and dynamic ligand exchange on sensitivity, selectivity, antifouling behavior, signal fidelity, and operational stability. Coordination-engineered architectures, including MXene–metal nanoparticle hybrids, metalloporphyrin- and phthalocyanine-functionalized MXenes, MXene–metal–organic framework heterostructures, and assemblies incorporating metalloenzymes, aptamers, and antibodies, have been evaluated across electrochemical, optical, field-effect transistor, photoelectrochemical, and piezoelectric sensing platforms. Coordination-controlled nanozyme catalysis, oxidative degradation, biofouling, and interfacial electron transfer pathways are further considered in the context of device reliability and clinical translation. Oxidative instability, heterogeneous surface chemistry, limited clinical validation, and the absence of standardized manufacturing processes remain major barriers to implementation. Emerging strategies for next-generation MXene-enabled HoC diagnostics include ligand-programmable interfaces, single-atom coordination sites, metalloprotein-inspired biointerfaces, computational ligand field engineering, and artificial intelligence-assisted materials discovery.