Multiplexed electrochemical biosensors: system-level design frameworks, signal decoding strategies and translational...

Food safety remains a pressing global public health concern, necessitating the development of analytical technologies that are sensitive, rapid, portable, and capable of simultaneous multi-analyte detection in decentralized settings. Multiplexed electrochemical biosensors (MEBs) have emerged as a highly promising platform, combining intrinsic electrochemical sensitivity with parallel detection capability, low cost, and amenability to miniaturization. Although significant progress has been achieved, a systematic, design-oriented synthesis of MEB strategies specifically tailored to food safety monitoring is still lacking. This review presents a comprehensive and structured analysis of the core design principles and application frameworks of MEBs for food safety surveillance. We critically examine key components including electrode configuration and spatial encoding architectures, multi-recognition element integration strategies, signal amplification mechanisms, multiplexed signal decoding methodologies, and system-level miniaturization and device integration. Representative applications are systematically categorized across major food safety hazards, encompassing veterinary drugs and pesticide residues, mycotoxins, heavy metal ions, and pathogenic microorganisms. Technical bottlenecks and translational challenges are discussed to provide a forward-looking perspective. MEBs provide an integrated analytical framework for high-density information acquisition through simultaneous multi-contaminant detection within compact electrochemical platforms. Current developments demonstrate robust analytical performance in complex food matrices such as milk, meat, cereals, and vegetables. However, a substantial portion of studies remain at the proof-of-principle stage using simplified matrices, including buffer systems and water samples. Bridging this gap between simplified validation systems and real food matrices remains a key translational challenge for decentralized food safety monitoring. To facilitate reliable real-world implementation, further advancements are required to enhance multiplexing scalability, analytical reproducibility, anti-interference capability, and long-term operational stability. Future progress will depend on rational system design, standardized performance validation, and the integration of intelligent data-processing strategies.