Stimuli-responsive (switchable) deep eutectic solvents in microextraction: Status, challenges and prospects in food safety and environmental analysis

Deep eutectic solvents (DESs) have attracted considerable attention as green extraction solvents, however, their application in microextraction is often limited by difficult phase separation, poor recyclability, and the need for additional separation steps. Stimuli-responsive or switchable deep eutectic solvents (S-DES) overcome these limitations through reversible hydrophilic-hydrophobic transitions triggered by external stimuli such as CO2/N2, pH, or temperature, enabling efficient extraction, rapid phase separation, and solvent reuse. This review critically examines the current status, challenges, and prospects of S-DES in microextraction for food safety and environmental analysis. The design principles, classification, and switching mechanisms of CO2/N2-, pH-, temperature-, magnetic-, photo-, and electro-responsive S-DES are discussed and critically assessed, together with the molecular interactions governing analyte extraction. Recent applications in liquid-phase microextraction for pesticides, antibiotics, pharmaceuticals, mycotoxins, heavy metals, and emerging contaminants are systematically evaluated. The role of computational tools, including COSMO-RS, density functional theory, molecular dynamics simulations, and machine learning, in understanding extraction mechanisms and guiding solvent design is also highlighted. Current challenges include limited validation in complex matrices, a lack of standardized switching protocols, and the underutilization of temperature-responsive systems. Future research directions focusing on thermo-responsive extraction platforms, multi-class contaminant extraction, and AI-assisted solvent design are discussed. S-DES show strong potential for developing greener, simpler, and more efficient microextraction methods for food safety and environmental monitoring.