An advantageous application of molecularly imprinted polymers in food processing and quality control

Abstract In the global market era, food product control is very challenging. It is impossible to track and control all production and delivery chains not only for regular customers but also for the State Sanitary Inspections. Certified laboratories currently use accurate food safety and quality inspection methods. However, these methods are very laborious and costly. The present review highlights the need to develop fast, robust, and cost-effective analytical assays to determine food contamination. Application of the molecularly imprinted polymers (MIPs) as selective recognition units for chemosensors’ fabrication was herein explored. MIPs enable fast and inexpensive electrochemical and optical transduction, significantly improving detectability, sensitivity, and selectivity. MIPs compromise durability of synthetic materials with a high affinity to target analytes and selectivity of molecular recognition. Imprinted molecular cavities, present in MIPs structure, are complementary to the target analyte molecules in terms of size, shape, and location of recognizing sites. They perfectly mimic natural molecular recognition. The present review article critically covers MIPs’ applications in selective assays for a wide range of food products. Moreover, numerous potential applications of MIPs in the food industry, including sample pretreatment before analysis, removal of contaminants, or extraction of high-value ingredients, are discussed.


Introduction
There is no healthy diet without healthy food.Therefore, the modern lifestyle requires easy access to high-quality food products (Wijayaratne et al. 2018).On the one hand, this trend supports the sustainable development of agricultural production and returns it to the traditional cultivation methods (Antonelli and Viganò 2018).On the other hand, it boosts the import of food products from exotic destinations.Both trends significantly increase production and delivery costs, while market competition enforces low-price maintenance.That tempts dishonest producers and suppliers (Soon et al. 2019;Ali and Suleiman 2018).Therefore, food product quality should be controlled at various manufacturing and distributing stages.
This control is very challenging in the global market era (Soon et al. 2019;Ali and Suleiman 2018).It is nearly impossible to track and control all food production and delivery chains not only for regular customers but also for the State Sanitary Inspections.Therefore, food manufacturers would try to unfairly raise the quantity and quality of the manufactured products (Silva et al. 2021).Furthermore, different chemicals used during farming, i.e., chemical fertilizers, pesticides, herbicides, antibiotics, antifungals, hormones, and food additives used by the food industry, including food preservatives, dyes, and artificial fragrances, can be present in food in significant amounts.Moreover, food products may be accidentally contaminated with heavy metal ions and toxins of industrial or natural origin.These toxins may be produced by mold or bacteria during food rotting.All of the above have adverse effects on the consumers' health.
Currently, certified laboratories are using accurate food quality and safety analysis methods.However, these methods are usually very laborious.They require well-trained and experienced employees and, frequently, costly instrumentation, e.g., high-performance liquid chromatography with mass spectrometry detection (HPLC-MS) (Silva et al. 2018).Therefore, the need to develop fast, robust and cost-effective analytical assays to determine food product contaminants should be highlighted.Moreover, newly developed analytical methods should easily be integrated with portable, hand-held devices, thus enabling on-spot sample analysis (Nelis et al. 2020).
Numerous electrochemical and optical methods of analytical signal transduction perfectly fulfill these requirements.However, their sensitivity and especially selectivity are far insufficient for successful sensors devising.Integrating selective recognizing units with the signal's transducer is Molecularly imprinted polymer; electrochemical chemosensor; optical chemosensor; food analysis; food toxin necessary to circumvent this deficiency (Khanmohammadi et al. 2020;Naresh and Lee 2021;Chen and Wang 2020).Applying biological recognizing units, including DNAs, aptamers, enzymes, monoclonal antibodies, cells, or even whole tissues, opened a route to devise various biosensors.Biosensors are sensitive and highly selective, and often specific.Therefore, abundant biosensors found their way to the market.Glucometers and pregnancy tests are the most widely offered biosensors.Despite their advantages, they suffer from several drawbacks.Their low durability originates from components of the biological origin.Therefore, they mostly serve as disposable devices.Alternately, e.g., multi-use glucometers require single-use sensing stripes with the glucose oxidase (GOx) or glucose dehydrogenase (GDH) enzyme immobilized on their surface.Such a cost-ineffective and high-waste approach may be accepted only in the healthcare field.More cost-effective sensors are in demand in food analysis, especially for controlling industrial-scale food production.For that purpose, chemically synthesized receptors may be immobilized on the transducer surface.Macrocyclic compounds, including cyclodextrins, crown ethers, and calixarenes, offer much better durability but at the expense of selectivity much lower than that of the bioreceptors.
Molecularly imprinted polymers (MIPs) compromise the durability of synthetic sensing materials with a high affinity to target analytes and selectivity of molecular recognition (Cieplak and Kutner 2016).Therefore, they effectively mimic natural molecular recognition.The present review critically covers the MIPs applications in chemosensors devised for selective food analysis using various transduction techniques and a wide range of tested products.Moreover, numerous potential applications of MIPs in the food industry, including sample pretreatment before analysis, removal of contaminants, or extraction of high-value ingredients, are discussed (Scheme 1).

Molecularly imprinted polymers (MIPs)
MIPs are an illustrative example of nature-inspired smart materials (Cieplak and Kutner 2016).In their matrices, MIPs contain molecular cavities imprinted during polymerization.For that purpose, template molecules are added to the solution for polymerization.Then, the polymer grows around these molecules during the polymerization.Later, these molecules' removal results in molecular cavities in the polymer structure, resembling template molecules with their shape, size, and orientation of recognizing sites.These cavities can recognize and capture only these molecules that spatially fit them.Moreover, carefully selected monomers, called functional monomers, are used for polymerization to increase the selectivity of this molecular recognition.These monomers contain recognition sites, including functional groups, heteroatoms, π-π conjugated systems, etc., that interact with binding sites of template molecules via covalent bonds, hydrogen bonds, electrostatic attractions, π-π stacking, as well as hydrophobic and van der Walls interactions (Scheme 2).These monomers form stable pre-polymerization complexes with template molecules in solution; thus, they are Scheme 1. outline of MiPs applications in the food industry and food quality control protocols.
built into the growing polymer during the polymerization.After template removal from the MIP, they stay as recognizing sites on the walls of the imprinted cavities, increasing the affinity of these cavities to the target analyte molecules and thus the binding selectivity.
Depending on their potential applications, MIPs are synthesized in many different forms, including bulk polymers, membranes, grains, micro-and nanoparticles (NPs), or thin films grafted on the solid support surfaces of diverse morphology.Several different polymerization procedures were employed for synthesizing MIPs, ranging from simple light-inducted free radical polymerization through emulsion polymerization and "living" polymerization to electrochemical polymerization.Details of MIPs synthesizing and characterizing have already been reported in various high-quality review articles (Uzun and Turner 2016;Wackerlig and Lieberzeit 2015;Niu, Chuong, and He 2016;Sharma et al. 2013;Beyazit et al. 2016).The readers who wish to explore the basics of molecular imprinting are encouraged to get acquainted with these articles.The present article focuses on the existing or potential applications of MIPs in food production and selective MIP chemosensors devised for food products analysis.

MIP sorbents application in food processing and control
The most common MIPs applications are separation materials where an unusually high degree of selectivity of the sorbents is utilized.For that, MIPs can be synthesized as irregular or spherical micro-or nanoparticles, membranes, or bulk materials that can be ground later.Prepared that way, MIPs may be used for dispersion extraction or as packing materials for solid-phase extraction (SPE) cartridges and high-performance liquid chromatography (HPLC) columns.The fast-growing field of MIP sorbents was reviewed in detail elsewhere (Turiel and Martin-Esteban 2010;Ashley et al. 2017).MIP-based separation materials are very convenient for sample preparation and purification.This opens up new opportunities for the food industry.Recently, several companies were established to develop and introduce MIP sorbents to the market.Only commercial examples are discussed in this chapter.

MIP SPE cartridges for sample pretreatment before food sample analysis
Developing new analytical methods for food product control and analysis may be a tremendous task.Usually, food products are inhomogeneous.They represent a complicated mixture of many different components in various concentration ranges.The analyte of interest may often be present in the analyzed sample at a concentration of several orders of magnitude lower than the interferences.Moreover, the HPLC system with a simple UV-vis or refractive index detection requires a relatively high analyte concentration.Therefore, food samples usually need laborious and time-consuming pretreatments to pre-concentrate the analyte and partially remove interferences that may foul and thus destroy the HPLC column.Hence, MIP sorbing materials appeared very useful in preliminary sample preparation procedures for HPLC assays (Scheme 3a).Recently, numerous MIP-SPE/ HPLC resins were commercialized (Table 1).Mainly, they are dedicated to clinical analysis.However, examples of MIP-SPE/HPLC resins application to food analysis were also reported.

Undesired ingredients removal from food products
Another possible application of MIP resins is the selective removal of undesired ingredients from food products.For that, a Ligar PL company was established in New Zealand to devise and fabricate MIPs to remove harmful food contaminants, including heavy metal ions or pesticides that may be extracted from liquid food products, i.e., drinking water, wine, cooking oil, or juice.Moreover, bitter, smoker, and unpleasant tastes or flavors may be removed from these products without significant loss of their desired properties.However, until now, this company has only presented successful removal of pyrimethanil fungicide from wine (Scheme 3b) (Petcu 2013(Petcu , 2015)).Ligar PL products have not yet been introduced to the worldwide market.But a high application potential of the purification procedure developed may be illustrated by MIP particles successfully devised by the K. Haupt group, in cooperation with the L'Oréal company, to remove odorous components of human sweat (Nestora et al. 2016;Mier et al. 2019).

Desired compounds extraction from natural sources
The under-estimated but presumably potentially the most profitable application of MIP particles is a selective extraction of high-value compounds from natural sources.Toward that, MIP particles can be dispersed in natural mixtures to absorb desired ingredients and then readily separated by sedimentation, filtration, centrifugation, or by applying a magnetic field in the case of magnetic MIP NPs (da Fonseca Alves et al. 2021;Aylaz et al. 2021).Therefore, this extraction may be performed under continuous-flow conditions, even on an industrial scale.In one important example, the G. Szekely group demonstrated extensive optimization of MIP particles synthesis and regeneration procedures (Kupai et al. 2017).Different L-phenylalanine methyl ester imprinted MIP particles were subjected to 100 adsorption-regeneration cycles.There was no loss of binding capacity within these 100 cycles for all examined MIP particles, even if the process was performed at elevated temperature (65 °C) and if methanol was used as the solvent for particle regeneration.Moreover, if divinyl benzene was applied as the cross-linking monomer, MIP particles' binding capacity was unaffected by regeneration neither in acidic nor basic aqueous solution during all 100 cycles.However, MIP particles synthesized with ethylene glycol dimethacr ylate or N,N'methylenebis(acrylamide) cross-linking monomers deteriorated after the first 20 sorption-regeneration cycles.Therefore, applying MIP particles for selective extraction seems economically justified if considering high extraction selectivity and potentially low cost of the MIP particles' synthesis.Accordingly, extraction of rosmarinic acid (Zahara et al. 2021) and quercetin (Pakade et al. 2013), as well as kaempferol (Pakade et al. 2013) from 3 kg of dried Salvia hypoleuca (Zahara et al. 2021) and 5 g of dried Moringa oleifera leaves (Pakade et al. 2013) were demonstrated, respectively.Moreover, in another example oleanolic acid imprinted polymer was applied to extract this acid from 150 mg grape pomace extract (Scheme 3c) (Lu et al. 2018).
After the purification using MIP loaded column, the content of oleanolic acid increased from 13.4% to 93.2%.Unfortunately, these procedures were performed only on the laboratory scale and have not been scaled up yet.Recently, Ligar PL has established a new daughter company, Amber Purification Ltd., devoted to developing a large-scale system to purify cannabinoid extracts from hemp.However, their products have not been commercialized yet.

MIP chemosensors for food products analysis
The HPLC assays mentioned above enable very selective and reproducible contaminants determination in food samples, thus ensuring highly reliable food quality control.However, these assays suffer from several disadvantages.They use high quantities of expensive solvents of very high purity.With the unit price exceeding 100,000 EUR, an HPLC system equipped with a mass spectrometry detector is mainly supplied to sanitary inspection laboratories and industrial-scale food manufacturers.It is inaccessible for small food manufacturers, not to mention individual farmers and food market customers.Importantly, these systems are unsuitable for in-field determinations.Therefore, all examined samples must be collected and transported to specialized laboratories.That highlights the urge to design inexpensive, hand-held chemosensors for fast and straightforward analyte determinations.The following sections describe the MIP chemosensors' application for various food sample testing, including determining particular contaminants or other relevant compounds.The most critical analysis details, the techniques used, and the food sample types are summarized in Tables 2 and 3.

MIP chemosensors for optical assays
Optical sensors are robust and inexpensive.For many procedures, optical assays are designed to give a readout that can be recorded by the naked eye of the operator, i.e., by observing color changes caused by the characteristic color reaction.MIPs may provide analyte preconcentration and selectivity enhancement for these procedures (Ye et al. 2018;Wu et al. 2018;Zhao et al. 2019;Feng et al. 2017).
Table 2. examples of MiPs application for optical sensing in food samples.no.Fluorescence transduction application results in assays of enhanced sensitivity.Accordingly, a competitive fluorescent assay for histamine in the fish extract was reported (Mattsson et al. 2018).MIP particles and a fluorescence-tagged histamine derivative were added to the sample solutions examined.Then, the histamine content in the solution was indirectly determined by evaluating the amount of fluorescent derivative remaining in the solution after mixing with MIP particles.In another report, a catalytically active AgNPs@MOF@MIP (where MOF denotes a metal-organic framework) nanocomposite was proposed (Bagheri et al. 2018).In the H 2 O 2 presence, terephthalic acid oxidation to fluorescent 2-hydroxyterephthalic acid was catalyzed.The patulin analyte inhibited this reaction by binding to MIP cavities, thus lowering the recorded fluorescence intensity.Moreover, a very fast and robust ELISA-like competitive assay was devised by depositing 17β-estradiol imprinted silica on the surface of a filter paper chemosensor (Scheme 4c) (Xiao et al. 2017).The target analyte competition with estradiol-labeled horseradish peroxidase (HRP) allowed for naked-eye 17β-estradiol detection by soaking the sensor in a solution of a colored reaction substrate.For milk samples containing 17β-estradiol, the color change was much less pronounced.

Group of contaminants
The above procedures require using costly and environmentally unfriendly chemicals.Moreover, most of these chemicals are being dumped into waste after use.Therefore, they are cost-ineffective and non-ecological.It is much more reasonable to synthesize MIP particles to serve as dyes themselves (Scheme 4a, I).Toward that, MIP particles containing co-polymerized fluorescent monomers were synthesized (Gao, Li, et al. 2014;Ashley, Feng, and Sun 2018;Li, Yin, et al. 2015).Moreover, an MIP film can be grafted on the surface of fluorescent quantum dots (QDs) (Sun et al. 2018;Wang, Fang, et al. 2017;Jalili et al. 2020;Wu, Lin, et al. 2017;Li, Jiao, et al. 2018;Fang et al. 2019;Cui et al. 2020;Shirani et al. 2021;Zoughi et al. 2021;Chen, Fu, et al. 2022;Sa-nguanprang, Phuruangrat, and Bunkoed 2022) or luminescent upconverting NPs (Liu et al. 2017).Those particles can be collected and regenerated after the assay and re-used many times.Recently, dual-emission MIP fluorescent particles were invented (Jalili et al. 2020).They were synthesized in two steps in a one-pot reaction.First, silica core particles containing (blue light)-emitting carbon QDs were synthesized.Then, a penicillin G imprinted mesoporous silica film containing (yellow light)-emitting carbon QDs was grafted as a shell.Due to spatial separation of (blue light)-emitting QDs, the penicillin G analyte binding in imprinted molecular cavities quenched the fluorescence of only (yellow light)-emitting carbon QDs.As tested on milk samples, a pronounced color change in the penicillin G analyte presence was observed even with the naked eye.In another report, using the sonication encapsulation method, luminescent and magnetic NPs were entrapped in MIP nanocomposites (Li and Wang 2013).Magnetic field-driven MIP nanocomposites separation from the sample solution decreased interference from other polycyclic aromatic hydrocarbons (PAHs), and only the phenanthrene target analyte significantly quenched the MIP luminescence.MIP nanocomposites emitted red light (λ = 620 nm).Therefore, the naked eye readily observed luminescence intensity changes due to phenanthrene presence.
Another procedure involved devising label-free optical assays.For that, MIPs were deposited on the surface of gold-layered SPR chips as thin films (Scheme 6a, I and V) (Jiang et al. 2015;Zhang et al. 2018), or MIP NPs' monolayers (Ashley et al. 2018;Yao et al. 2016;Çimen, Bereli, and Denizli 2022).In this case, analyte binding in MIP caused a change in the electric permittivity of the film that was in contact with an ultra-thin gold film deposited on the SPR chip surface.This binding shifts the evanescing light angle and wavelength, at which resonance with surface plasmon occurs.Thus, light is being absorbed.However, this approach is usually dedicated to determining macromolecular compounds, and SPR determination sensitivity to small-molecule compounds is relatively low.Therefore, Au NPs (Altintas 2018) and magnetic MIP NPs (Yao et al. 2013) were applied to enhance the sensitivity of SPR chemosensors.Moreover, the SPR spectrometer readout depends on the angle of the light evanescence.It makes chemosensors susceptible to mechanical vibrations and thus useless for in-field assays.Therefore, an MIP film was deposited by electropolymerization on the surface of an optical fiber to overcome this deficiency (Li, Zheng, et al. 2018).To this end, fibers were unclothed using a sharp blade, and then the cladding of sensing sections was entirely removed by immersing them in an HF solution.Finally, a 5-nm thick Cr underlayer and a 50-nm thick Au layer were consecutively sputtered on the sensing section of the optical fiber sensor.This Au layer served as the working electrode during deposition by electropolymerization of the MIP film, and a transducer sensitive to analyte binding to the MIP imprinted cavities.In another example, an MIP film was deposited on a 100-nm diameter Au nanodisks array (Guerreiro et al. 2017).Thus, changes in localized surface plasmon resonance were monitored.
Very robust label-free optical chemosensors based on MIP photonic structures were proposed.To this end, a magnetic field-assisted colloidal crystal of magnetic MIP NPs was deposited (Scheme 4d) (You, Cao, and Cao 2016;You et al. 2017).In another approach, MIP films of the inverse opal structures were synthesized using silica beads as sacrificial molds (Scheme 4e) (Yang, Peng, et al. 2017;Li et al. 2019;Wu et al. 2019;Qiu et al. 2020).In both cases, analyte binding in the MIP film caused this film to swell and or to change its electric permittivity.In turn, that generated a significant change in the film color originating from Bragg diffraction.That way, toxins in various food samples were determined.The MIP chemosensors based on the colloidal crystals or the inverse-opal structures seem promising candidates for hand-held portable device fabrication applications.That is because of their robustness, independence from any external power supplies, and the possibility to detect analytes just by naked eye observation of the color change.
Furthermore, surface-enhanced Raman spectroscopy (SERS) transduction was combined with MIP recognition.The advantages of SERS sensors, including high sensitivity and qualitative analyte identification, were improved by MIPs selectivity.MIPs were applied for sample pretreatment in the most robust approach before the SERS assay to pre-concentrate and purify the target analyte (Feng et al. 2017;Feng et al. 2013;Wu et al. 2016;Hua et al. 2018;Feng et al. 2018;Zhao et al. 2019).Moreover, an Au NPs suspension was applied for extraction to collect the analyte, namely, histamine, accumulated on the MIP SPE column (Gao, Grant, and Lu 2015).In more advanced procedures, the bulk MIPs were decorated with Au (Xie et al. 2017;Wang et al. 2020) and Ag (Hu and Lu 2016) NPs.Alternately, a thin MIP film was grafted on the surface of Au NPs (Zhou et al. 2020;Yin, Wu, et al. 2018) or ZnO@TiO 2 @Ag NPs (Chen, Wang, et al. 2022).Similarly, a filter paper was coated with carbon ink on one side and decorated with silver dendrites on the other (Scheme 5a) (Zhao, Liu, et al. 2020).Then, an MIP was deposited by electropolymerization inside this paper.Ag NPs were synthesized on top of the MIP to enhance the SERS signal.In these procedures, analyte extraction and SERS determination were performed simultaneously.Various vegetable samples were tested in this manner.In another report, MIP microparticles served as a thin-layer chromatography (TLC) stationary phase (Gao et al. 2015).After developing and drying, the TLC plate was decorated with Au NPs, and the SERS signal was recorded (Scheme 5b).That enabled rapid Sudan I determination in paprika powder with minimal sample pretreatment.

Electrochemical MIP chemosensors
Electrochemical sensors are gaining more and more interest because of their robustness, easy operation, and highly reproducible determinations.However, they usually suffer from low selectivity.The biological receptor immobilization on the electrode surface enables circumventing this disadvantage.Despite high selectivity and sensitivity, prepared that way, electrochemical biosensors reveal many deficiencies, mainly originating from the fragility of the biological recognition units used for their fabrication.Therefore, electrodes coated with selective MIP films (Scheme 6a, I and 6a, II) have recently attracted more and more interest.So far, numerous examples of MIP film-coated electrodes have been reported for possible application in food quality control.Charged compounds can easily be determined with potentiometry (Shirzadmehr, Afkhami, and Madrakian 2015;Anirudhan and Alexander 2015).This technique usually covers a broad concentration range.But, by its nature, the potentiometric sensor's response linearly depends on the logarithm of concentration.Hence, it is insensitive to small changes in the analyte concentration.
If the target analyte is electroactive, it can be determined by recording its oxidation or reduction current changes with time by chronoamperometry at a selected constant potential applied (Lian et al. 2013;Turco, Corvaglia, and Mazzotta 2015;Turco et al. 2018;Amatatongchai et al. 2018).But there is a substantial limitation.That is, the target analyte must be the only electroactive component of the sample in the studied potential range.Voltammetric techniques enable partial overcoming of this deficiency.However, the faradaic currents originating from electrode reactions are overlapped by interfering capacity currents in a simple representation (Yang, Zhao, and Zeng 2016;Zhang et al. 2017;Deng, Xu, and Kuang 2014;Hassan et al. 2019;Li, Liu, et al. 2015).These undesired currents are subtracted in advanced voltammetry techniques, e.g., differential pulse voltammetry (DPV).Therefore, DPV sensitivity is very high, and the limit of detection (LOD) is low (Liu et al. 2022).Importantly, these techniques are dedicated to determining electroactive analytes (Yang, Zhao, and Zeng 2016;Zhang et al. 2017;Deng, Xu, and Kuang 2014;Hassan et al. 2019;Li, Liu, et al. 2015).If the target analyte is electroinactive, MIP chemosensors can signify their advantage.Electroinactive analytes may be determined using the so-called "gate effect" (Sharma et al. 2019).For that, a redox probe is added to the sample solution, and changes in the faradaic current caused by the changes in MIP film properties incurred by analyte binding are recorded (Sharma et al. 2019).Interestingly, redox probes can also be immobilized inside the MIP film (Lach et al. 2021).Moreover, such advanced techniques as electrochemical impedance spectroscopy (EIS) not only provide insight into the mechanism of the electrode processes (Sharma et al. 2019) but may also serve as a sensitive transduction tool for analyte determination (Lach et al. 2017;Lach et al. 2019;Ayerdurai, Cieplak, et al. 2021;Munawar et al. 2020;Shamsipur, Moradi, and Pashabadi 2018).In another example, capacitive impedimetry at MIP film-coated electrode was applied to determine cancerogenic aromatic amines in meat samples (Ayerdurai, Garcia-Cruz, et al. 2021).
Electrochemical redox processes can be combined with optical transduction to enhance the sensitivity and selectivity of determinations involving MIPs.For that, quenching of electrochemiluminescence (ELC) resulting from analyte binding by an MIP was applied (Li, Liu, et al. 2017;Zhang et al. 2022;Wang et al. 2022;Zhao et al. 2022;Jin et al. 2018).
MIP thin films were deposited by electropolymerization on the electrodes decorated with carbon QDs (Li, Liu, et al. 2017;Zhang et al. 2022), Cu nanoclusters (Wang et al. 2022), and Ru(bpy) 3 2+ decorated Fe 2 O 3 microfibers (Zhao et al. 2022) or upconverting NPs (Jin et al. 2018;Scheme 6c).Au NPs, GO, and rGO were deposited on the electrodes to increase the electrode surface area and conductivity.Thus, reagents enabling electron transfer in their excited states were electrochemically generated on NPs more efficiently.Analyte molecules binding in MIP cavities disturb this process.Therefore, it was possible to determine target analytes at very low concentrations.

Other types of MIP chemosensors
Molecular imprinting was also combined with several other transduction techniques.For instance, MIP films were successfully deposited on the surface of quartz crystal resonators (Scheme 6a, IV) (Lach et al. 2017;Pietrzyk et al. 2009;Liu et al. 2014;Ebarvia, Ubando, and Sevilla 2015;Fang et al. 2017;Lin et al. 2018;Dayal et al. 2019;Zhao, He, et al. 2020;Ceylan Cömert et al. 2022).Then, the MIP film mass changes caused by analyte binding were measured by piezoelectric microgravimetry using a quartz crystal microbalance (QCM).This microgravimetry is a very sensitive technique enabling mass change measurements down to nanograms, i.e., below a monolayer coverage.However, QCM is very difficult to miniaturize into a hand-held device.On the contrary, sensors based on field-effect transistors (FETs), especially the extended-gate field-effect transistors (EG-FETs), seem to ease miniaturizing because of their robustness.Moreover, the high sensitivity and selectivity of EG-FET chemosensors make them attractive candidates for portable analytical devices useful for in-field measurements.For instance, rapid gluten determination in semolina flour was reported (Scheme 6a, III) (Iskierko et al. 2019).
Noteworthy, a microfluidic MIP-based device for carbofuran determination in fruit and vegetable samples was fabricated (Scheme 6b) (Li, Li, et al. 2018).This device consisted of two compartments connected with microchannels.One compartment contained the MIP that ensured sample purification and analyte preconcentration, while the other served as an electrochemical cell with a working electrode decorated with the DNA aptamer targeted to carbofuran.This aptamer ensured additional enhancement in both sensitivity and selectivity of the chemosensor.In another procedure, microfluidic chips containing microreactors connected to miniaturized thermistors were reported (Athikomrattanakul, Gajovic-Eichelmann, and Scheller 2011;Cornelis et al. 2019).These microreactors contained MIP NPs (Athikomrattanakul, Gajovic-Eichelmann, and Scheller 2011) or a surface imprinted MIP film (Cornelis et al. 2019).Then, the thermistors determined the heat released because of the strong interactions of the target analyte (Athikomrattanakul, Gajovic-Eichelmann, and Scheller 2011) or bacteria (Cornelis et al. 2019) with MIP molecular cavities.

Miscellaneous applications
Interestingly, MIP chemosensors were applied not only for undesired contaminants determination in food samples but also for food quality assessment.Accordingly, wine astringency was estimated.For that, the LSPR MIP chemosensor imprinted with saliva proteins was designed to study the interactions of these proteins with wine samples (Guerreiro et al. 2017).Presumably, wine ingredients bound saliva proteins, thus causing these proteins to shear and feel dryness.The wine astringency estimated by the MIP chemosensor and expressed in pentagalloyl glucose units (PGG) agreed well with the wine evaluation by a professional taster.

Challenges and future prospectives
Polymer synthesis is easily scalable and can be implemented on an industrial scale.Therefore, MIPs can be readily synthesized in the form of bulk polymers, sponges, membranes, micro-, and nanoparticles.Recently, MIP-based SPE columns were introduced to the market.Because of a relatively high price, commercial applications of these MIPs are limited to sample pretreatment in clinical analysis.However, with the increase in the production volume, MIP resins price should drop so much that they will find applications in the food industry.Possibly, first in veterinary, later in food quality control, and, finally, in food products processing.
However, several important issues should be resolved before implementing the MIPs synthesis in the industry.One deficiency is the necessity of using templates to synthesize MIPs.These templates are removed from MIPs within the final steps of their synthesis and then they are being dumped to waists.Because toxic compounds, i.e., heavy metal ions, mycotoxins, pesticides, antibiotics, and hormones, are usually used as templates, producing waists containing these compounds may constitute a severe risk to human health and the environment.This issue may be resolved by the approach proposed by Piletsky's (Canfarotta et al. 2016) .and Haupt's (Ambrosini et al. 2013;Xu et al. 2016) research groups.Both groups have developed protocols for automated MIP NPs synthesis on solid supports.In this approach, template molecules are immobilized on a glass bead (solid support) surface.Next, MIP NPs are grown around these immobilized templates, and then washed out.Thus, the template stays on the solid support surface and can be used multiple times for MIP NPs synthesis.Moreover, the toxic template does not contaminate synthesized MIP, nor toxic wastes are produced during the synthesis.
The most critical challenge in introducing MIPs to the food processing industry seems to be preventing microplastic contamination.This contamination accompanies any production and application of polymers nowadays.That is, MIPs may be a source of not only microplastic in the environment but also may contaminate processed food products.Microplastic contamination is not only a severe environmental burden but also has significant adverse effects on human health (Rainieri and Barranco 2019;De-la-Torre 2020;Kwon et al. 2020).One solution to this problem is the synthesis of magnetic MIP NPs.Those MIP NPs can be readily removed from samples and collected by simply applying a magnetic field (da Fonseca Alves et al. 2021;Aylaz et al. 2021;Siciliano et al. 2022).Another approach may be to use biodegradable polymers for MIP synthesis.For example, the imprinted chitosan (Zouaoui et al. 2020;Bagheri and Ghaedi 2019), cellulose (Wen et al. 2022;Cao et al. 2021), and crosslinked poly(lactide-co-glycolide) dendrimers (Kumar, Jha, and Panda 2019;Gagliardi, Bertero, and Bifone 2017) have already been reported.Moreover, dimeric vanillin derivatives were recently applied as monomers for synthesizing a photodegradable polymer (Singathi et al. 2022).Importantly, this polymer decomposed in a controlled manner into vanillin dimers upon irradiation with UV light of λ = 300 nm.If it were applied for MIP NPs synthesis, these MIP NPs would be stable until irradiating with the light of the above wavelength.Then, they would decompose to harmless vanillin dimers.Similarly, NPs of polycoumarin were synthesized by irradiation with UV light (Avó, Lima, and Jorge Parola 2019).Importantly, photodimerization of coumarin is a reversible process if it is irradiated with light of a defined wavelength (Wolff and Görner 2010).Therefore, it would also be possible to photodegrade such NPs.However, none of these two polymers has yet been applied in MIP synthesis.Moreover, it is possible to synthesize MIPs from materials that are biocompatible and harmless to the environment.Namely, imprinted polydopamine (Palladino, Bettazzi, and Scarano 2019;Siciliano et al. 2022), polyscopoletin (Bognár et al. 2022;Jetzschmann et al. 2019;Di Giulio, Mazzotta, and Malitesta 2020), and silica (Susanti and Hasanah 2021;Susanti, Mutakin, and Hasanah 2022) were reported.These materials occur in the natural environment and seem to have no adverse influence on living organisms.
Presumably, most of the above challenges are solvable.Notably, the most significant advantage of MIPs fabrication consists in their versatility.That is, if an MIP-based product, e.g., an SPE cartridge, HPLC column, chemosensor, etc., is implemented into mass production, only limited optimization is needed to implement other analogous products selective for other analytes.Therefore, most implementation costs must be covered for the first product in the manufacturer's offer.But if this investment pays off, extending the range of products will be less costly.Therefore, we assume that if MIP-based products mentioned in the present article prove to be a commercial success, within the next few years, the offer of MIP-based analytical tools will be extended, and their price will be significantly reduced.That will open the field for the widespread application of these products.

Conclusions
Molecularly imprinted polymers (MIPs) exemplify the idea of smart materials.As selective sorbents, MIPs have recently been introduced to the market.With the increasing number of applications, their cost will decrease, and their availability will increase.Due to their unique properties, including high selectivity and durability, MIPs may find numerous applications in food manufacturing, food safety, and food quality control.MIP-based chemosensors fabrication is a constantly growing field.Several examples of robust, very sensitive, and selective MIP chemosensors reported in the literature suggest that the MIP-using technology is sufficiently mature to enter the market even within the current decade.Hand-held devices, especially those based on visual readout with naked-eye, may find interest from both sides, i.e., end-user customers and farmers who would like to control quality of their food products during production.It is easy to envision that in the not-too-distant future, customers will come to a food market equipped with hand-held analytical devices of the size of a mobile phone, capable of testing the quality of food products on the spot by themselves.

Disclosure statement
We confirm that none of the coauthors has any conflict of interest to be declared.

Funding
The National Science Center of Poland financially supported the present research (Grant SONATA no.2018/31/D/ST5/02890 to M.C.).
Moreover, the present scientific work was partially funded from the financial resources for science in 2017-2021, awarded by the Polish Ministry of Science and Higher Education for implementing an international co-financed project.Furthermore, the present publication is part of a project that has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 711859.

Scheme 2 .
Scheme 2. the flowchart of a general procedure of MiP synthesis.adapted from sharma et al. (2013).
Scheme 3. (a) Food sample pretreatment before sample analysis.an example of ochratoxin a (ota) HPlC determination in beer, red wine, and grape juice samples(Cao, Kong, et al. 2013) and GC-Ms determination of bisphenol compounds in breast milk samples(deceuninck et al. 2015).(b) removal of food contaminants during processing.Purification of wine contaminated with pyrimethanil(Petcu 2013(Petcu , 2015)).(c) High-value compounds extraction.Molecularly imprinted sPe of oleanolic acid from grape pomace extract(lu et al. 2018).

Scheme 4 .
Scheme 4. (a i) a typical structure of MiP nanoparticles synthesized for optical assays.(a ii and a iii) an example of a fluorescent MiP optical assay.Carbon Qd@MiP core-shell fluorescent nPs applied for tartrazine determination in saffron tea.adapted from Zoughi et al. (2021); (b) Colorimetric determination of pyrethroid metabolite in fruit juice and beverages based on adsorption-desorption on imprinted silica nPs and color reaction with KMno 4 , adapted from Ye et al. (2018).a competitive assay for naked-eye semi-quantitative determination of 17β-e 2 hormone in milk using MiP-coated nylon membrane and horseradish peroxidase (HrP) labeled 17β-e 2 , adapted from Xiao et al. (2017); (d) Photonic structures of magnetic MiP particles assembled in a magnetic field applied for colorimetric determination of melamine, adapted from You, Cao, and Cao (2016); (e) Color changes of inverse-opal MiP film to methyl anthranilate concentration changes allow semi-quantitative detection of the target analyte in wine samples, adapted from wu et al. (2019).

Scheme 5 .
Scheme 5. (a) Multilayer paper sers chemosensor based on star-shaped silver dendrites, MiP film, and ag nPs for imidacloprid determination in the cucumber, chives, and soybean samples.adapted from Zhao, liu, et al. (2020); (b) Combining tlC on the MiP film-coated plate with sers assay for selective sudan i determination in the paprika extract samples.adapted from Gao et al. (2015).

Table 1 .
Commercial solid-phase extraction (sPe) columns and their application in the food industry.no.
a non-linear response.b linear in a semi-log scale.

Table 3 .
examples of MiPs application for non-optical sensing in food samples.no.
a linear in a semi-log scale.b non-linear response.