In food safety control, there is growing interest in technologies capable of detecting contaminants quickly, selectively, and, if possible, directly in-line. This is where supramolecular sensors come into play—systems based on reversible molecular interactions that can recognize specific analytes, such as pesticides, mycotoxins, veterinary drug residues, heavy metals, or spoilage markers.

The review “Advanced supramolecular food safety sensing technology: principles and applications”, published in Food Chemistry in 2025, explains how supramolecular sensors are promising tools for food safety control, thanks to their ability to selectively recognize contaminants through noncovalent interactions and host–guest systems. The article highlights applications for the rapid detection of chemical residues, mycotoxins, additives, and other food hazards, while noting that the complexity of real-world matrices and scalability to an industrial scale remain the main challenges for practical application.

Supramolecular macrocycles

Rapid advances in supramolecular chemistry—particularly in host-guest systems—and in chemosensing technologies are offering new strategies for food safety analysis. Supramolecular macrocycles are molecular receptors characterized by internal cavities capable of selectively binding target molecules or ions through weak, reversible, noncovalent interactions, such as electrostatic interactions, hydrophobic effects, π interactions, ion-dipole bonds, and van der Waals forces. The strength of these interactions is described by the association constant, which can be measured using techniques such as isothermal titration calorimetry. It is precisely the ability to control affinity, selectivity, and spatial complementarity between the receptor and the analyte that makes these systems particularly interesting for molecular recognition. Among the most studied macrocycles are crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillararenes. These structures feature adjustable sizes and shapes, numerous recognition sites, and good potential for chemical functionalization. From an automation perspective, the appeal of these systems lies in the ability to couple molecular recognition with an optical, fluorescent, or electrochemical transduction platform, so that the interaction between receptor and analyte can be converted into a measurable, digitizable signal that can potentially be integrated into in-line control systems. Looking ahead, signals of this type could be integrated into production line monitoring and control systems, contributing to automatic or semi-automatic decisions regarding the blocking, segregation, or re-inspection of non-compliant products. However, in real-world food processing contexts, such performance must be carefully evaluated, as the presence of proteins, fats, sugars, salts, and other matrix components can influence the binding between the receptor and the analyte. For this reason, supramolecular macrocycles represent a promising platform, though one that still needs to be further established in industrial settings.

Applications in Food Safety Detection

The most immediate applications involve the detection of chemical contaminants even at low concentrations, by exploiting changes in fluorescence or color resulting from specific interactions between the pesticide and the receptor. In some cases, sensor arrays are used—that is, sets of receptors that are not perfectly specific but are capable of producing a “fingerprint” of response.

This approach is useful when contaminants have similar chemical structures and must be distinguished not by a single signal, but by an overall profile. Another important field is the detection of mycotoxins critical for grains, nuts, spices, wine, coffee, and animal feed. The challenge lies in the need to detect them at extremely low concentrations, with high selectivity, and in the presence of many natural interferences. Supramolecular systems, especially when combined with nanomaterials or fluorescent platforms, can improve sensitivity and response speed. The analysis of antibiotic and veterinary drug residues is also a promising area of research, as supramolecular sensors allow for the development of selective recognition systems based on the shape, charge, and functional groups of the target molecule. The detection of heavy metals represents another area of application. In this case, recognition can be achieved through receptors capable of selectively coordinating metal ions with an optical or electrochemical signal. A particularly interesting aspect of supramolecular sensing is the ability to detect markers of freshness and spoilage, such as biogenic amines, histamine, putrescine, cadaverine, trimethylamine, and ammonia, which can be detected by functionalized materials capable of changing color or fluorescence depending on their concentration. Applications of this type could be integrated into smart labels, active films, or packaging systems capable of providing visual information on a product’s preservation status. There is significant industrial interest in supramolecular sensors for process control systems, but their application to real matrices requires great care, as proteins, salts, fats, sugars, and natural substances can interfere with the binding between the receptor and the analyte.

Integration into the production line

Supramolecular chemistry has amply demonstrated its effectiveness in vitro, as evidenced by several studies, but it has yet to prove its ability to withstand the demands of a production line and overcome obstacles such as compatibility with CIP cycles, operational continuity, and fouling of sensitive surfaces. In food fluid processing lines, a sensor- d into the process stream may be exposed to alkaline and acidic washes, mechanical stress, and, in some plants, high temperatures during sanitization phases. Some supramolecular receptors may offer stability advantages over biological systems based on enzymes or antibodies, but their robustness must still be verified under actual process conditions, especially in the presence of wash cycles, variations in pH and temperature, and fouling.