Metal-organic framework-enabled electrochemiluminescence biosensing: Design principles, signal amplification...

Electrochemiluminescence (ECL) is a highly sensitive analytical technique for trace-level biosensing, benefiting from a high signal-to-noise ratio, controllable excitation, and negligible background interference. However, practical ECL sensor performance is often constrained by sluggish interfacial electron transfer, inefficient co-reactant utilization, and limited luminophore stability. Metal-organic frameworks (MOFs), featuring tunable porosity, modular architectures, and multifunctional chemical environments, have emerged as versatile platforms to address these limitations, while simultaneously introducing new design complexities. This review critically examines recent progress in MOF-enabled ECL biosensing from a sensor design perspective, with a particular focus on signal amplification strategies and their associated performance trade-offs. We analyze how amplification approaches-including nucleic acid-based reaction cascades, self-enhanced ECL systems, and co-reactant regulation strategies-interact with MOF structures to influence sensitivity, dynamic range, reproducibility, and operational robustness. The multifunctional roles of MOFs as nanoreactors, carriers for luminophores and co-reactants, and components of hybrid conductive or catalytic architectures are evaluated in terms of analytical benefit versus synthetic and operational complexity. Finally, key challenges hindering real-world implementation, including signal reproducibility, fabrication scalability, and device integration, are discussed. Design-oriented guidelines are proposed to assist in selecting appropriate MOF architectures and amplification schemes for specific biosensing tasks, aiming to bridge the gap between proof-of-concept demonstrations and practical ECL sensor development for biomedical and environmental applications.