ReviewRecent advances in analytical strategies and microsystems for food allergen detection
Introduction
Food allergies are becoming an increasingly important public health problem in modern society with continued global economic development (Hossny et al., 2019). It has been reported that 5%–10% of people have experienced food-related allergic symptoms (Park, 2015). Currently, the means to treat food allergies is not clearly understood, and the only known prevention method is avoiding the consumption of allergen-containing foods. Excessive food restriction due to the misdiagnosis of food allergies can lead to nutritional disorders and lower the quality of life. Allergies to certain foods can cause a wide variety of unpredictable reactions, such as skin symptoms, allergic rhinitis, asthma symptoms, and anaphylaxis, depending on the intake amount and individual sensitivity (Al-Rabia, 2016). Therefore, patients who are sensitive to certain foods should completely avoid the corresponding allergens (Hosu et al., 2018). However, because the same production line is often used to process and produce various food products, it is difficult to confirm whether these foods are cross contaminated with allergens (Pape, 2009).
To address these challenges, food manufacturers and companies require reliable detection techniques to accurately identify food allergens and label processed foods with warnings to protect sensitive consumers from food allergies (Ross et al., 2018). In fact, the European Union (EU) has established labeling regulations for 14 allergens. However, this approach has limitations, because it does not account for the possible existence of other unreported allergens (Allen et al., 2014). To provide a fundamental solution to this problem, it is necessary to develop compact and convenient allergen detection devices that can be used by consumers (Iqbal et al., 2018). Food allergy testing methods that have been widely used in recent years include investigations of reactions and symptoms after food intake, both in vivo, such as skin reaction tests, patch tests, elimination diets, and food trigger tests, and in vitro, including tests for the detection of basophil histamine release, eosinophils, histamine, cytokines, or immunoglobulin G (IgG) (Manea et al., 2016). Disadvantageously, these testing methods are time-consuming or must be performed under the supervision of a medical professional or well-trained technician. Consequently, the development of new reliable detection methods that can overcome these drawbacks is essential for end users who are sensitive to food allergens (Turnbull et al., 2015).
In addition to the methods mentioned above, many foods safety and industry related researchers have developed methods to detect food allergens using enzyme linked immunosorbent assay (ELISA), polymerase chain reactions (PCRs), and chromatographic methods (Picariello et al., 2011, McGrath et al., 2012). The most used rapid testing methods in food allergen detection are antibody-based detection methods that enable the analysis of specific target samples. Enzyme-linked immunosorbent assays (ELISAs) are powerful tools for detecting and quantifying specific proteins in complex mixtures. There are several types of ELISAs (Su et al., 2013, Sharma et al., 2016, Sharma et al., 2016), with the most widely used being the sandwich ELISA (Van Hengel et al., 2007). In Addition, liquid chromatography-mass spectrometry (LC-MS) is considered a gold standard and has been increasingly used by many foods processing companies to verify the effectiveness of safety management in the field (Picariello et al., 2011, McGrath et al., 2012). However, these technologies are laborious, time-consuming, and expensive when simultaneously analyzing voluminous samples, although more advanced analytical systems have been developed in recent years. In addition, poly- or monoclonal antibodies are sometimes unstable under harsh experimental conditions and are not cost effective for mass production. Nucleic acid-based methods such as PCR offer molecular specificity but have complex sample preparation and potential for false positive (Sin et al., 2014). For these reasons, the effective detection of food allergens is hindered by the effects of various treatment processes and food matrices on trace amounts of allergens and by interference from specific markers in food. Therefore, more studies on the effects of food processing on allergens should be conducted (van Hengel, 2007) and it is necessary to develop devices in a form that can be measured in real-time, on-site by consumers. A recent survey by an EU project confirmed a rapidly growing interest in the food industry for the development of more accurate and advanced allergen detection devices (Poms et al., 2010). Indeed, rapid testing methods for food allergens have become an important tool for validating hygiene practices, thus minimizing the risk of cross-contamination.
Biosensors are emerging as an alternative technology to overcome the problems associated with antibody-based detection assays (Pilolli et al., 2013). Biosensors consist of four basic parts including a sample preparation, a bioreceptor, a transducer, and a signal amplification component (Fu et al., 2019). The bioreceptor may be an allergen-specific antibody (Crosson et al., 2010), a single-stranded DNA or RNA capable of hybridizing with an allergen-specific DNA probe, aptamer (Sun et al., 2012), cell (Jiang et al., 2014), molecularly imprinted polymer (MIP) (Sundhoro et al., 2021), bacteriophage (Peltomaa et al., 2016), or an affinity peptide isolated by the phage display technique to directly recognize the target allergen (Cho et al., 2021). Theoretically, biosensors are very selective and sensitive because they use a specific reaction between a target molecule and recognition element. In addition, biosensors can be applied to complex samples, and it is possible to detect multiple analytes quickly and inexpensively. As biosensors are easy to use and capable of high-level automation, allergens can be monitored directly and online in real time along a food production chain. Nevertheless, several issues remain to be addressed, including food matrix effects, the effects of food processing on the efficiency of allergen detection, the defined lifespan of biological substances, inactivation by other substances, and the fact that heat sterilization cannot be applied (Neethirajan et al., 2018, Neethirajan et al., 2018). In recent years, many achievements have been reported in the field of innovative biosensor applications. Furthermore, advances in materials science and nanotechnology toward the fabrication of different types of nanomaterials with various shapes and/or sizes have provided new possibilities for technological applications (Khan et al., 2019). The high specificity of biological receptors and their integration with nanomaterials have provided exciting new alternatives to existing optical, electrical, electrochemical, and micromechanical analysis methods (Briza Perez-Lopez, 2011). In this review, we have tried to provide an overview of applications aimed especially at food allergen detection, followed by the detection of; the food safety and food contamination field then complement the list.
Section snippets
Classification of symptoms and progression routes in food allergies
Adverse reactions to foods, a term which is widely used to refer to abnormal clinical reactions related to food intake, can be classified as food intolerances or food allergies based on the associated pathological and physiological reactions (Fig. S1) (Park, 2015). Although some of the symptoms of food allergies and food intolerances are similar, it is important to fully understand the differences between these reactions (Crowe, 2019). In the case of food intolerances, digestion is difficult,
Overview of the technologies for food allergen detection
The presence of allergens in food can cause abnormal immune responses via either defined pathways or undefined complicated reactions. Therefore, there is an urgent need for the early and accurate diagnosis of food allergens. As mentioned above, food allergy and food intolerance have a fundamentally different mechanism for the occurrence of symptoms. Unlike food intolerance, food allergy is an immune reaction that occurs between antigens and antibodies, whereas food intolerance is not. This
Conclusion remarks and future perspectives
Food allergies have been considered a critical issue in the food safety area. Thus, the development of sensitive, and selective, efficient methods for identifying and quantifying food allergens is of great importance in the food industry. The issues associated with conventional detection methods can be mitigated by developing biosensors integrated with advanced materials science technology. Currently, the prevalence of food allergies is increasing worldwide. Therefore, the development of
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (NRF-2019R1A2C2084065, NRF-2020K1A3A1A30103959).
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These authors equally contributed to this study.