Single-atom nanozyme-enabled immunosensors: from atomic design to analytical applications

Immunosensors achieve highly selective detection through specific antigen-antibody recognition. However, their signal-amplification strategies, which are commonly based on natural enzymes or noble-metal nanomaterials, often suffer from poor stability, high cost, and susceptibility to matrix interference. Although nanozymes have emerged as promising alternatives, their heterogeneous active domains and poorly defined electronic structures often result in less controllable uncontrollable catalytic behavior. Single-atom nanozymes (SANs), featuring atomically dispersed active sites and tunable coordination/electronic structures, establish well-defined structure-activity relationships and provide a mechanistic link between atomic-scale active-site engineering and sensing performance through integration with immunorecognition interfaces. In this review, recent advances in SAN-enabled immunosensors are systematically summarized from the perspective of the structure-mechanism-application relationship. We discuss active-site engineering strategies, characterization techniques, and catalytic mechanisms that govern enzyme-mimicking activity, followed by representative signal-amplification pathways and sensing platforms across different detection modes. Emerging applications in clinical diagnostics and food and agricultural safety are highlighted. Finally, the key challenges toward practical translation and future perspectives, including AI-guided materials discovery, mechanism-guided design, multifunctional sensing systems, and real-world deployment, are discussed. This review aims to provide fundamental design principles for the rational development of next-generation high-performance single-atom immunosensors.