Click Reactions: A Paradigm Shift in Food Chemical Residue Testing

Chemical residues in food pose a global health challenge, which necessitates sensitive and reliable detection methods. Current techniques (e.g., chromatography and immunoassays) remain limited by operational complexity, insufficient sensitivity, and poor adaptability for on-site use. Click chemistry has emerged as a novel solution, offering rapid, specific, and ultrasensitive detection of food chemical residues, such as pesticides, antibiotics, and hormones-contaminants that pose significant health threats through chronic exposure. This review outlines the principles and classifications of click reactions, emphasizing their selectivity, mild reaction conditions, and modular design. Integrating biosensors enhances molecular recognition and signal amplification, enabling on-site screening in complex food matrices. We critically evaluate recent click chemistry-based sensors, detailing their design strategies (e.g., probe functionalization and nanomaterial engineering) and optimization via advanced transduction mechanisms. Key challenges-including matrix interference, reagent stability, and cost-are addressed through molecular imprinting, microfluidic miniaturization, and AI-driven system refinement. Future advancements will focus on integrating green chemistry to reduce environmental impact, developing multiplexed platforms for high-throughput detection, and expanding applications to emerging contaminants such as microplastics and biotoxins. These innovations promise to redefine food safety standards with scalable, next-generation analytical tools.