A state-of-the-art review of trends in molecularly imprinted polymers in the clean-up of pesticides in environmental samples

ABSTRACT

Molecularly imprinted polymers (MIPs) are synthetic materials designed with specific molecular recognition capabilities. They are created through a process where monomers are polymerized in the presence of a template molecule, resulting in the formation of cavities or binding sites within the polymer matrix that are complementary in shape and functionality to the template molecule. MIPs offer the advantages of stability, selectivity and versatility in molecular recognition, and they have found applications across various scientific and industrial fields. The review describes some extraction procedures for the clean-up of pesticides in environmental samples before instrumental analysis. Synthesis procedures for MIPs, and the advantages and disadvantages of MIPs for the extraction of pesticides in environmental samples are discussed. In addition, an effort has also been made to condense the information regarding MIPs. Finally, drawbacks and prospects for MIPs in dispersive solid phase extraction (d-SPE) are also appraised.

KEYWORDS:

• Molecularly imprinted polymers
• pesticides
• d-SPE
• sample clean-up
• extraction

1. Introduction

In agriculture, pesticides have played a significant role in protecting crops and improving productivity and yield. Pesticides are a category of organic pollutants that include, among others, organophosphorus, organochlorine, carbamates and pyrethroids. Organophosphorus pesticides include chlorpyrifos and glyphosate. Organochlorines also include lindane and heptachlor (Wan Ibrahim et al., 2015).

The exposure to pesticides can be heightened due to various factors such as incorrect selection, overuse, and over-reliance on pesticides in agricultural practices. Additionally, improper harvesting time, poor and insufficient storage practices, use of unauthorized or banned products, mixing of multiple products, inappropriate application techniques, unsuitable spraying equipment, testing by the tongue to assess concentration strength, non-literate farmers, lack of training by relevant institutions, lack of minimal protective clothing, and improper labelling of pesticide containers can also contribute to increased exposure to pesticides. These findings have been reported in various studies conducted by Chen et al. (2011) and Damalas and Eleftherohorinos (2011). The practice of utilizing pesticide containers for the purpose of storing food and water may also potentially increase the likelihood of exposure to pesticides (Damalas & Eleftherohorinos, 2011).

Inhalation during spraying, dermal absorption through the skin, and oral absorption of tainted foods, beverages, and animal products are all possible routes for human exposure to pesticides (Bakırcı et al., 2014). Multiple exposures’ cumulative and synergistic effects might also be taken into account. Due to the use of harmful pesticides that are illegal in developing nations, lax import regulations, and a lack of oversight and monitoring, farmers in Ghana and other developed nations are more at risk of exposure (Darko & Acquaah, 2007).

According to scientific research (Akoto et al., 2015; Boulanouar et al., 2018; Garcia & Freitas, 2011) prolonged exposure to pesticides, causes cancer, immune response suppression (immunotoxicity), hormone disruption, decreased intelligence, abnormal male reproduction, developmental defects, cardiovascular disease, birth defects, diabetes and chemical sensitivity. There have also been reports of nausea, headaches, and skin and eye irritations (Mostafalou & Abdollahi, 2017). According to Köhler and Triebskorn (2013), pesticides can damage the ecosystem by harming non-target animals including birds, bees and fish.

The need for developing a reliable analytical approach for measuring pesticide residual levels in the environment can therefore not be overstated. It is crucial to find the most effective way to extract and quantify pesticide residue to reduce waste, cut down on laboratory time, boost productivity, and cut costs.

Dispersive solid phase extraction (d-SPE), magnetic solid phase extraction (MSPE), stir-bar sorptive extraction (SBSE) and solid phase micro-extraction (SPME) are all offshoots of solid-phase extraction, which offer many benefits over liquid-liquid extraction (López Grío et al., 2010). However, the conventional sorbents (carbon, silica and polymeric materials) that are typically used in these techniques have drawbacks of lack of selectivity and sensitivity (Azizi et al., 2020); Binsalom et al. (2016); Speltini et al. (2017). To address these limitations, scientists have created molecularly imprinted polymers (MIPs), which can be thought of as synthetic antibodies. Their stability, durability, relative simplicity of customizing to new analytical targets, cost savings, reusability, and excellent recognition and selectivity have made them useful in a variety of applications i.e. sensors, insecticides, drug delivery, catalysis, chromatography among others (Azizi & Bottaro, 2020); Pichon et al. (2019); Simões et al. (2014). They have gained a lot of interest as SPE sorbents for removing unwanted matrix and concentrating desired analytes (Xin et al., 2013).

MIPs are formed by the polymerization reaction between a functional monomer like methacrylic acid, a cross-linker to provide some rigidity to the system, a solvent, and an initiator together with the template (analyte of interest). The selected monomer should have some sort of attraction with the functional groups on the template molecule. This process produces an extremely cross-linked polymer with binding sites that are specific and selective (in terms of shape, size and functionalities) to the target molecule. After completion of the polymerization process, the template molecule is washed off, thereby creating cavities congruent to the template molecule (Figure 1). These cavities are now primed for targeted recombination with the template molecule (Sarafraz-Yazdi & Razavi, 2015).

Figure 1. Molecular polymer imprinting mechanism.

Molecularly imprinted polymers (MIPs) are synthetic materials that are designed to selectively recognize and bind to target molecules including pesticides. They have proved to be excellent replacements for some of the more conventional sorbents. Due to their stability, durability, simplicity of customizing to novel analytical objectives, cost savings, reusability and high selectivity, they have garnered interest in many applications (Zhu et al., 2005), especially as sorbents in SPE and d-SPE for extract cleanup and pre-concentration of the target analyte from a complicated matrix.

In this review, MIPs as sorbent materials for pesticide residue clean-up in environmental samples will be discussed. Synthesis methods for MIPs will also be highlighted.

2. Sample extraction methods

The process of sample preparation poses a significant hindrance to the precise and efficient analysis of minute amounts of pesticide residues. The objective of the sample preparation process is to extract small quantities of analytes from a vast quantity of intricate matrices while minimizing the interferences from the food matrix. The standard procedures for preparing samples involve the processes of sampling, uniform mixing, extraction, and clean-up. The efficacy of pesticide residue analysis is significantly impacted by the extraction and clean-up process (Lu et al., 2021). For the study of pesticide residues, conventional sample extraction techniques, particularly liquid-liquid extraction (LLE), have been employed extensively. However, the rigorous experimental process makes these approaches time- and solvent-consuming and susceptible to analyte loss. Liquid-liquid extraction (LLE), supercritical-fluid extraction (SFE), pressurized-liquid extraction (PLE), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), gel permeation chromatography (GPC), solid-phase extraction (SPE), matrix solid-phase dispersion (MSPD), solid-phase micro-extraction (SPME), quick, easy, cheap, effective, rugged and safe extraction method (QuEChERS), cloud point extraction (CPE) and liquid phase micro-extraction (LPME) are various extraction techniques. Table 1 demonstrates the use of some of these techniques for extracting analytes in samples.

Table 1. Conventional extraction methods used for analyzing samples

Extraction Method	Example	Reference
Liquid-Liquid Extraction (LLE)	Extraction of organophosphorus pesticides from water samples using LLE.	Farajzadeh et al. (2015); Niu et al. (2017)
Supercritical-Fluid Extraction (SFE)	Extraction of pesticide residues from agricultural products using SFE.	Saito-Shida et al. (2014); Yousefi et al. (2021)
Pressurized-Liquid Extraction (PLE)	Extraction of herbicides from soil samples using PLE.	Barp et al. (2023); Zinedine et al. (2010)
Microwave-Assisted Extraction (MAE)	Extraction of pesticide residues from food samples using MAE.	Manousi et al. (2022); Wu et al. (2015)
Ultrasound-Assisted Extraction (UAE)	Extraction of pesticide residues from fruits using UAE.	Sajid & Alhooshani (2020)
Gel Permeation Chromatography (GPC)	Cleanup of pesticide extracts using GPC.	Martínez-Domínguez et al. (2014)
Solid-Phase Extraction (SPE)	Extraction of pesticide residues from water samples using SPE.	Garcia et al. (2018); Q. Han et al. (2014)
Solid-Phase Micro-Extraction (SPME)	Extraction of pesticide residues from water samples using SPME.	Moreno-González et al. (2020)
QuEChERS	Extraction of pesticide residues from various matrices using QuEChERS.	Anastassiades et al. (2003); Lehotay et al. (2005)

2.1 Liquid-liquid extraction

Among the various techniques employed for sample preparation, liquid-liquid extraction (LLE) can be considered the most traditional and widely used method. Before undergoing the LLE process, solid samples are subjected to various mechanical treatments such as grinding, softening, mincing, pressing, or pulverizing to achieve a fine and uniform particle size. The resulting extracts are subjected to centrifugation, concentration, and/or purification before final analysis. The efficiency of analyte extraction in the LLE process is primarily influenced by the differences in solubility or distribution of the target compound between the two liquid phases. The target compound selectively transfers or partitions from one liquid phase (the feed phase or source phase) to the other liquid phase (the solvent phase or extract phase) based on its solubility characteristics. Common solvents used for liquid-liquid extraction include acetonitrile, chloroform, and ethylacetate (Roque et al., 2019).

2.2 Solid phase extraction

Solid phase extraction (SPE) is a sample preparation technique used to separate and purify target analytes from a mixture using a solid sorbent material. It is widely employed in analytical chemistry to extract and concentrate analytes from complex matrices such as environmental samples, biological fluids, and pharmaceutical formulations.

Dispersive solid phase extraction (d-SPE), magnetic solid phase extraction (MSPE), stir-bar sorptive extraction (SBSE), and solid phase micro-extraction (SPME) are all offshoots of solid-phase extraction, which offer many benefits over liquid-liquid extraction (Cazorla-Reyes et al., 2011). However, the conventional sorbents (carbon, silica and polymeric materials) that are typically used in these techniques have drawbacks of lack of selectivity and sensitivity (Azizi & Bottaro, (2020); Binsalom et al. (2016); Speltini et al. (2017)

The SPE process involves the following steps:

• Conditioning: Before sample loading, the solid sorbent material is typically conditioned with a solvent or a series of solvents. Conditioning helps to remove any impurities, pre-equilibrate the sorbent, and ensure consistent and reproducible analyte retention.

• Sample loading: The sample, which may contain the target analytes along with interfering substances, is passed through the conditioned solid sorbent material. The sorbent can be packed in a cartridge, disk, or other solid-phase extraction formats.

• Retention: The target analytes selectively interact with the sorbent material, while other components in the sample matrix are not retained or are minimally retained. This retention can occur through various mechanisms, such as adsorption, partitioning, or ion exchange, depending on the nature of the sorbent and analytes.

• Washing: After loading the sample, the sorbent is typically washed with one or more solvents to remove any remaining impurities or interferences that may have been retained. The choice of washing solvents depends on the nature of the sample matrix and the desired selectivity.

• Analyte elution: The target analytes are eluted from the sorbent using an appropriate elution solvent or a combination of solvents. The elution solvent should have a higher affinity for the analytes than the sorbent, facilitating their desorption and collection in a separate vial or container.

• Concentration and recovery: The eluted analytes are typically concentrated by evaporating the solvent or using techniques such as nitrogen blow-down or solid-phase microextraction (SPME). This step allows for a higher concentration of the analytes, making them more amenable to subsequent analysis by techniques such as chromatography or spectroscopy.

SPE offers several advantages in sample preparation, including selectivity, concentration and removal of interfering substances. It can be used for a wide range of analytes, from small organic compounds to larger biomolecules. Various sorbent materials are available, such as silica, bonded silica, polymer-based materials, molecularly imprinted polymers, C₁₈, florisil (magnesium silicate), activated carbon, primary secondary amine (PSA), graphitized carbon black (GCB) and multiwalled carbon nanotubes (Qiang Q. Han et al., 2012).

SPE has gained widespread acceptance as a viable alternative to LLE for sample preparation because it provides flexibility and versatility in method development (Kosma et al., 2007).

2.3 QuEchERS method

QuEChERS denotes quick, easy, cheap, effective, rugged, and safe. In this method, extraction of the analyte of interest from the sample matrix is done through the utilization of water-miscible solvents, typically acetonitrile, and high concentrations of salt and/or buffering agents. The process of selecting a solvent is crucial to minimize the co-extraction of compounds. Phase separation is induced during the extraction process through the utilization of salts (Figure 2). Buffers are utilized to modulate the pH and dehydrate the system. The process of sample cleanup is crucial in minimizing interference during subsequent analysis. This is because interference has the potential to cause damage to analytical instrumentation and make it difficult to identify and quantify the analyte. The QuEChERS method differs from traditional sample cleanup techniques that employ SPE tubes. Instead, QuEChERS involves combining large quantities of SPE sorbents with the sample extract to facilitate the cleanup process. The purpose of using sorbents in clean up is to eliminate matrix interferences that may coextract with the analytes of interest. PSA, C₁₈, and GCB sorbents are commonly utilized to eliminate various compounds such as sugars, lipids, sterols, organic acids, proteins, carotenoids, chlorophyll, and other pigments from samples before conducting instrumental analysis.

Figure 2. Schematic diagram of QuEChERS method.

2.4 Solid phase micro-extraction (SPMS)

Solid phase microextraction (SPME) involves the utilization of a fiber that has been coated with an extraction phase, which may consist of a liquid (polymer), a solid (sorbent), or a combination of the two. The fiber that has been coated is encased within a needle designed for protection and affixed to a holder that bears a resemblance to a syringe. Upon exposure of the fiber to a sample, the analytes present in the sample undergo partitioning from the sample into the stationary phase until a state of equilibrium is attained. The coating on the fiber enables the extraction of compounds from the sample. This can occur through absorption for liquid coatings or adsorption for solid coatings. Following a predetermined duration of extraction, the fiber is extracted and subsequently introduced into a chromatographic apparatus, typically either gas chromatography (GC) or high-performance liquid chromatography (HPLC), for desorption and analysis. The process of desorption in gas chromatography involves thermal means, whereas, in high-performance liquid chromatography, desorption is achieved through the use of a solvent to transfer analytes into a liquid phase (J. Huang et al., 2012).

2.5 Dispersive solid phase extraction

Dispersive solid phase extraction (d-SPE) is a sample preparation technique that involves the integration of solid-phase extraction principles with a dispersion step. The process is frequently employed to extract and purify analytes from intricate matrices. The process of d-SPE involves the addition of a solid sorbent material, such as silica, MIPs, C₁₈, or graphitized carbon black to the sample matrix. This material is specifically chosen to interact with and retain the desired analytes. The sorbent functions as an adsorbent, effectively trapping the desired analytes while reducing the presence of interfering substances.

The d-SPE process typically involves the following steps:

1. Sample dispersal: The sample matrix, often a liquid, is mixed or shaken vigorously with the solid sorbent material. This disperses the sorbent particles throughout the sample, facilitating contact between the sorbent and analytes.

2. Analyte sorption: During the dispersal step, the target analytes partition between the sample matrix and the solid sorbent. The analytes preferentially adsorb onto the sorbent due to their affinity for the sorbent surface or specific interactions (e.g. hydrophobic interactions).

3. Separation: After the dispersal and sorption step, the sorbent particles are separated from the sample matrix. This can be achieved through techniques like centrifugation, filtration, and magnetization where the sorbent is collected while the sample matrix is discarded.

4. Cleanup (optional): In some cases, a cleanup step may be performed to remove any remaining interfering substances or unwanted components. This can involve rinsing the sorbent with specific solvents or washing steps to further improve analyte purity.

5. Analyte elution: The analytes of interest are then desorbed or eluted from the sorbent using a suitable solvent. The elution solvent should have a higher affinity for the analytes than the sorbent material, enabling their release into a separate vial or container for subsequent analysis.

D-SPE offers several advantages in sample preparation, including simplicity, cost-effectiveness, and efficient extraction of target analytes. It can be used for various analytes and sample matrices, such as environmental samples, food samples, and biological fluids. The technique provides improved selectivity and sensitivity by reducing matrix interference and concentrating analytes of interest, making them suitable for further analysis using techniques such as chromatography or spectroscopy.

3. History of molecularly imprinted polymers

Living organisms possess the remarkable ability to detect chemical alterations in their metabolic processes and surroundings through the utilization of specialized receptors. This enables them to exhibit a high level of selectivity and sensitivity in recognizing these changes. The effectiveness of these interactions is dependent on the specific binding that occurs between receptors and their corresponding ligands. The binding interactions rely on the intricate recognition properties observed in antibodies and enzymes. These properties enable them to differentiate between their specific target analytes and other compounds that have similar structures (Shahhoseini et al., 2022).

The high specificity, selectivity, and sensitivity of these biological receptors make them a compelling choice for sensor development. Devices that depend on biological molecular recognition parts frequently suffer from issues related to storage and operational stability. The process of synthesizing the molecular receptor typically involves multiple steps and can be quite complex. Additionally, the total quantity produced of the final product is often low. The complex and expensive process of obtaining biological molecules has prompted researchers to explore the synthesis of antibody mimics in the field of chemistry (B. Li et al., 2014).

The preparation of ‘host’ molecules capable of recognizing ‘guest’ species can be achieved through a technique called ‘molecular imprinting’. This technique, known as template polymerization, offers a simpler approach to achieve the desired results (Li et al., 2020).

Scientist Polyakov found that when silica polymers were created in the presence of a specific molecule, they could preferentially absorb that molecule (Woźnica et al., 2023). The aforementioned finding represents the initial scholarly reference to molecularly imprinted polymers (MIPs). Researchers conducted further experiments on Polyakov’s molecular imprinting technique using a range of template molecules on silica gel.

Dickey (1955) utilized methyl orange as template molecules in their study, while Curti and Colombo (1952) employed (S)-10-camphor sulfonic acid. Similarly, Beckett and Anderson (1957) also utilized alkaloid molecules in their research. The molecules utilized as templates in all of these studies were organic. These works are widely recognized as fundamental contributions to the development of molecular imprinting methodologies.

The development of modern imprinting methodology in Europe during the 1970s and 1980s involved the contributions of several individuals. Klaus Mosbach from Sweden, Günter Wulff from Germany, Borje Sellegren from Amsterdam, and Karsten Haupt from France were key figures in this process (Woźnica et al., 2023). Significantly, several studies have found that MIPs can imitate specific functions of biological molecules such as receptors and enzymes (Khan et al., 2018; Sajini & Mathew, 2021). The demonstration of covalent imprinting in 1972 was achieved through the integration of functional groups into the imprinted absorbent (Takagishi & Klotz, 1972; Wulff & Vietmeier, 1989). Mosbach’s later work showcased the utilization of non-covalent interactions, also referred to as non-covalent imprinting, in the field of imprinting techniques (Mosbach, 1994; Sellergren, 1997).

MIPs have found widespread use in various applications owing to their notable properties, including strong affinity and selectivity, as well as their ability to withstand extreme variations in temperature, pressure, and pH. Synthesizing them is a more cost-effective process, and they have a long storage life, maintaining their recognition sites for many years at room temperature (Daryanavard et al., 2013).

Molecular imprinting involves the polymerization of a functional monomer and cross-linking agent in a suitable porogenic solvent while incorporating the compound(s) to be imprinted (known as templates). The polymer matrix maintains recognition cavities that match the template concerning size, shape and functionality even after the template is removed (Farooq et al., 2018). The imprinted polymer exhibits the ability to selectively re-bind to the template molecule in a mixture of different chemical species.

MIPs offer significant benefits due to their notable selectivity and affinity towards the target molecule employed during the imprinting process. When comparing imprinted polymers to biological systems like proteins and nucleic acids, it is evident that imprinted polymers possess superior physical stability, strength, immunity to increased temperature and pressure, as well as inactivity towards acids, bases, metal ions and organic solvents. Furthermore, it is worth noting that the synthesis of these polymers is more cost-effective. Additionally, these polymers have a significantly long storage life, allowing them to maintain their recognition capacity for several years even when stored at ambient temperatures (Daryanavard et al., 2013).

3.1 Preparation of molecularly imprinted polymers

MIPs are produced by combining a functional monomer, such as methacrylic acid (MAA), a crosslinker, such as ethylene glycol dimethacrylate together with the template molecule in a suitable porogenic solvent. The template molecule can be either the target analyte or a similar analog with comparable chemistry and shape (Azizi & Bottaro, 2020). Polymerization is commonly initiated through the use of heat or UV stimulation of an initiator. Following the process of polymerization, the template molecules are eliminated, resulting in a polymer that possesses cavities. These cavities exhibit a complementary nature in terms of their shape, size, and functional groups when compared to the target molecule (Orihara et al., 2018). The superior recognition abilities of molecularly imprinted polymers (MIPs) in comparison to non-imprinted polymers (NIPs) can be attributed to the relationship between the template molecule and a specific functional group in the pre-polymerization complex. When the MIPs come into contact with the analyte in the sample matrix, these connections are quickly restored. This feature provides MIPs with a notable edge compared to conventional non-selective sorbents.

3.1.1 Templates

In molecularly imprinted polymers, the template molecule plays a crucial role in the synthesis process. The template molecule is the target molecule that the MIP is designed to recognize and selectively bind to. It serves as a ‘molecular mold’ or reference that shapes the polymer matrix during the polymerization process, leading to the creation of specific recognition sites or imprints. Examples of some templates are shown in Figure 3. It is chosen based on the desired target analyte or compound that the MIP is intended to recognize. It can be a small organic molecule, a biomolecule, a metal ion, or any other molecule of interest. The template molecule should have structural features that allow for specific interactions with the functional monomers in the polymerization mixture.

Figure 3. Structure of some templates.

During the MIP synthesis, the template molecule is typically mixed with the functional monomers and the cross-linking agent. The functional monomers self-assemble around the template molecule through non-covalent interactions, such as hydrogen bonding, electrostatic interactions, or hydrophobic interactions. The polymerization then proceeds, resulting in the formation of a polymer network with complementary imprinted sites that match the shape, size, and functional groups of the template molecule.

After the polymerization, the MIP is subjected to a post-polymerization treatment to remove the template molecule. This step is crucial to create cavities or recognition sites within the polymer matrix that can selectively bind to the target molecule. The removal of the template molecule leaves behind imprints that have a complementary shape and chemical functionality to the template, enabling the MIP to selectively recognize and bind the target molecule.

The template molecule serves as a reference or imprinting agent for the creation of specific recognition sites in the MIP. Once the template is removed, the resulting MIP can be used for various applications, such as selective separations, sensors, assays, drug delivery systems, and catalysis.

3.1.2 Functional monomers

In MIPs, functional monomers are a key component of the polymerization mixture. These monomers are chosen based on their ability to interact with the template molecule and form specific binding sites within the polymer matrix. Functional monomers typically possess chemical groups or functionalities that can participate in non-covalent interactions with the template molecule, such as hydrogen bonding, electrostatic interactions, or hydrophobic interactions. These interactions are crucial for the formation of complementary binding sites that can selectively recognize and bind the target molecule. The selection of functional monomers depends on the nature of the template molecule and the desired binding interactions. For example, if the template molecule has hydrogen bond acceptor sites, functional monomers with hydrogen bond donor groups can be chosen. Similarly, if the template molecule has hydrophobic regions, hydrophobic functional monomers can be used. Examples of some functional monomers are shown in Figure 4. During the polymerization process, the functional monomers self-assemble around the template molecule and undergo polymerization, resulting in the formation of a three-dimensional polymer network. The template molecule is subsequently removed, leaving behind cavities or imprints that possess a complementary shape and chemical functionality to the template. These imprints act as specific recognition sites within the MIP for the target molecule. The interaction of the monomer and the template is determined by an equilibrium. To promote the formation of the complex, it is typically necessary to add an excess of functional monomers compared to the amount of moles of the template. The ratio between the template and functional monomer is typically 1:4. The presence of different arrangements of the template-functional monomer complex results in a heterogeneous distribution of binding sites in the final MIP. Methacrylic acid (MAA) is commonly used by researchers because it possesses the dual capability of acting as both a hydrogen bond proton donor and a hydrogen bond acceptor (Vasapollo et al., 2011).

Figure 4. Structures of some functional monomers.

The choice and combination of functional monomers play a critical role in determining the selectivity, affinity, and binding properties of the resulting MIP. By carefully selecting appropriate functional monomers, MIPs can be tailored to recognize and bind specific target molecules with high selectivity and affinity.

3.1.3 Cross linkers

The cross-linker is an important component in the synthesis of molecularly imprinted polymers. It serves to create a three-dimensional network within the polymer matrix, resulting in the formation of stable and robust MIPs with well-defined recognition sites. This network provides stability and rigidity to the MIP, allowing it to retain its shape and integrity during subsequent use. The cross-linker is typically a bifunctional monomer that possesses two or more reactive groups capable of forming covalent bonds with the functional monomers. These reactive groups can be vinyl groups, methacrylate groups, or other functional moieties that can participate in polymerization reactions (Anirudhan & Alexander, 2015).

The choice of cross-linker depends on several factors, including the desired porosity of the MIP, the type of polymerization method employed, and the compatibility with the functional monomers. Commonly used cross-linkers in MIP synthesis include ethylene glycol dimethacrylate (EGDMA), trimethylolpropane trimethacrylate (TRIM), divinylbenzene (DVB), and pentaerythritol triacrylate (PETA), (Figure 5) among others.

Figure 5. Structures of some cross-linkers.

The amount of crosslinker used in the polymerization mixture affects the porosity and binding characteristics of the resulting MIP. Higher cross-linker concentrations generally lead to a more rigid and less porous polymer matrix, resulting in higher affinity but lower binding capacity. On the other hand, lower cross-linker concentrations can result in a more flexible and porous matrix, allowing for higher binding capacity but potentially lower affinity.

The role of the cross-linker in the polymeric network is to impart enough rigidity to maintain the structure of the polymer and the spatial conformation of the functional groups (Muhammad et al., 2012). Usually, an 80% cross-linking degree is applied for the preparation of imprinted polymers (Cormack & Elorza, 2004). The recognition properties of the MIP as well as its mechanical properties are strongly dependent on the degree of cross-linking and on the nature of the crosslinker. Highly cross-linked systems demonstrate lower template release, as reported by Salian and Byrne (2013).

3.1.4 Porogen

The selection of the polymerization solvent plays a critical role in the successful creation of a MIP. This is because the choice of solvent can either enhance or inhibit particular reactions between the template molecule and the monomers. In addition, the structural properties and porosity of the material can be adjusted by manipulating the choice and quantity of solvent used. According to Speltini et al. (2017), most molecular imprinting processes that utilize non-covalent synthesis are typically carried out in aprotic and low-polarity organic solvents such as chloroform, dichloromethane and toluene. The distinction between template and functional monomer is primarily determined by the presence of electrostatic forces and hydrogen bonding.

Porogens can be classified into two main categories: organic porogens and inorganic porogens. Organic porogens include solvents such as acetonitrile, chloroform and toluene, which are compatible with the monomers and initiators used in the polymerization process. Inorganic porogens on the other hand, can include salts, silica particles or other solid materials that are later removed by dissolution or extraction (Haupt et al., 2011; Nestora, 2017).

3.2 Strategies for molecular imprinting

3.2.1 Covalent imprinting

The development of covalent imprinting was primarily attributed to Wulff and Vietmeier, (1989). The proposed method involves the covalent binding of the template and functional monomer during a pre-polymerization step. Subsequently, the template is eliminated from the polymer matrix by splitting the covalent bonds before the washing process. Sorbents that are created using covalent imprinting exhibit a higher degree of precision and uniformity in their binding sites compared to those produced through the non-covalent method (Garcia & Freitas, 2011). One significant drawback of covalent-based molecularly imprinted polymers is the requirement for a well-designed monomer-template complex that can readily establish reversible covalent bonds with the desired shape and chemistry to effectively capture targets from aqueous systems. If the covalent bonds between the MIP and the target need to be reformed during the polymer’s use, it can lead to slow association kinetics. Water analysis typically does not involve the utilization of covalent strategies (Azizi & Bottaro, 2020).

3.2.2 Non-covalent imprinting

The non-covalent approach was initiated by Mosbach and his colleagues (1994). The most frequently employed synthesis method is known for its simplicity (Speltini et al., 2017). It involves mixing a template with a functional monomer, a porogenic solvent, cross-linking agents, and catalysts or polymerization initiators. The formation of specific binding sites occurs through the self-assembly process involving the template and the functional monomer. The formation of a stable complex with the template typically occurs through dipole interaction, hydrogen bonding, or ion pairing (Sarafraz-Yazdi & Razavi, 2015). The imprinted molecule is easily removed through solvent extraction after polymerization using this method. It is important to acknowledge that the pre-polymerization complex in this approach is a reversible system at equilibrium. The stability of this system is determined by the affinity constants between the imprint molecule and functional monomers. The presence of variation in the imprinted binding sites may be a result of this phenomenon (Bouvarel et al., 2020).

3.2.3 Semi-covalent imprinting

The utilization of a hybrid system known as semi-covalent imprinting has been proposed as a means to reduce non-specific restrictions (C. He et al., 2007). The methodology involves the covalent binding of layout atoms to the monomers before polymerization, which enhances the selectivity. The analyte demonstrates a binding affinity through non-covalent interactions, which results in a longer equilibrium time compared to covalent approaches (J. Liu et al., 2019). Semi-covalent molecularly imprinted polymers exhibit several advantageous characteristics, such as having more uniform binding sites and facilitating rapid mass transfer to both organic and inorganic polymeric structures.

In their study of the imprinting of the pesticide format, Tang et al. (2016) used clenbuterol as the template and methacryloyl chloride as the monomer for polymerization. They also utilized EGDMA as the crosslinker in their experiments. Hydrolysis conducted in acidic conditions resulted in the removal of the template and the formation of molecularly imprinted polymers with cavities that can accommodate noncovalent interactions, specifically hydrogen bonding. The polymer demonstrated rapid equilibrium in capturing the analyte within a 20-minute timeframe, exhibiting a high level of specificity. The adsorption capacity was found to be 7.34 mg for MIPs and 1.99 mg for NIPs (non-imprinted polymers).

3.3 Strategies for polymerization

Several polymerization methods have been utilized in the preparation of MIPs. Some of these techniques are discussed below and also shown in Table 2.

Table 2. Polymerization methods

Polymerization Method	Monomer	Initiator	Cross-linker	Solvent(s)	Template Molecule	Researchers
Bulk Polymerization	Methacrylic acid (MAA)	AIBN(Azobisisobutyronitrile)	Ethylene glycol dimethacrylate (EGDMA)	Methanol, acetonitrile, toluene	Bisphenol A	D. Li et al. (2017)
	MAA	APS (Ammonium persulfate)	Trimethylolpropane trimethacrylate (TRIM)	DMF (Dimethylformamide)	Cefalexin	Wen et al. (2019)
Precipitation Polymerization	Acrylamide	AIBN	Ethylene glycol dimethacrylate (EGDMA)	Acetonitrile, methanol, water	Flavonoids	W. Zhang et al. (2022)
	Methacrylic acid (MAA)	AIBN	Ethylene glycol dimethacrylate (EGDMA)	Acetonitrile, chloroform	Enrofloxacin	W. Wang et al. (2021)
Emulsion Polymerization	Methacrylic acid (MAA)	AIBN	Ethylene glycol dimethacrylate (EGDMA)	Cyclohexane, SDS (Sodium dodecyl sulfate)	Diethylstilbestrol	Guo et al. (2019)
	Methacrylic acid (MAA)	AIBN	Trimethylolpropane trimethacrylate (TRIM)	Methanol, acetonitrile, water	Tetracycline	Zeng et al. (2021)
Suspension Polymerization	Methacrylic acid (MAA)	AIBN	Ethylene glycol dimethacrylate (EGDMA)	Acetonitrile, toluene, water	Quercetin	Sundhoro et al. (2021)
	Methacrylic acid (MAA)	AIBN	(EGDMA)	Acetonitrile, toluene, water	Quercetin	Liang et al. (2020)
Surface Imprinting	Methacrylic acid	AIBN	Ethylene glycol dimethacrylate (EGDMA)	Tuolene	Propazine	Geng et al. (2015)

3.3.1 Bulk polymerization

This is the most common technique (normally called traditional or conventional polymerization) used for the polymerization of MIPs (Farooq et al., 2018). It is normally supported by photo or thermal initiation. MIPs synthesized by this method have several advantages, including enhanced stability, robustness, and resistance to a diverse array of pH levels, temperatures, and organic solvents (Azizi & Bottaro, 2020). It is the simplest method because the constituents (functional monomer, template, porogen, cross-linker) are all put together in a reaction vessel, then degassed and sealed. The final product in the form of a block monolith is then crashed, ground, and sieved. However, this process, because of the grinding stage does not favor the binding sites i.e. makes them unavailable. The final products also have irregular sizes and shapes. There is also the problem of waste of fine particles which results in low yield. The adsorption capacity and selectivity of the final sorbent produced is very low. Bulk polymerization also consumes a lot of time (Azizi & Bottaro, 2020 ; Farooq et al., 2018; Speltini et al., 2017).

3.3.2 Precipitation polymerization

This process uses copious volumes of solvent. The polymer chain grows and precipitates at the bottom because of insolubility in the liquid phase (Garcia & Freitas, 2011). Polymers obtained from this technique have controlled sizes but their shapes unfortunately remain irregular and colloidal. Precipitation polymerization is, however, a rather complex and labor-intensive technique.

Dai et al. (2011) employed precipitation polymerization to synthesize a diclofenac imprinted polymer. They reported better adsorption capacity, about ten times more than that produced by bulk polymerization when they increased solvent volume from 200 to 1000 mL. They attributed the greater adsorption capacity to the greater surface area and a more substantial number of binding sites for recognition of target analytes.

3.3.3 Suspension polymerization

The concept was first proposed by Mosbach (1994). The process entails dissolving all the ingredients necessary for polymerization in an appropriate organic solvent, such as water, perfluorocarbon, or mineral oil. Next, the mixture is introduced into a separate solvent that is incapable of mixing with the original solvent. The production of tiny droplets is initiated by intensive stirring after the induction of polymerization (Farooq et al., 2018; Speltini et al., 2017). The method produces particles with sizes ranging from 10–100 µm.

3.3.4 Emulsification polymerization

This is an improvement in precipitation polymerization. The experimental setup utilizes a two-phase system consisting of immiscible oil and water. The components involved, namely the functional monomer, cross-linker, and template, are initially mixed in water through emulsification. Stabilizers are subsequently introduced to the dispersed phase to prevent diffusion within the continuous phase. The elimination of surface surfactants in this procedure contributes to its environmental friendliness.

In their study, Y. Sun et al. (2016) employed silica nanoparticles as a stabilizer to investigate the selective determination of seven bisphenols from sediment samples using a dummy imprinted polymer. In addition to the stabilizer mentioned, researchers have also utilized other stabilizers such as attapulgite, graphene oxide (GO), and halloysite nanotubes (Al₂Si₂O₅(OH)₄.nH₂O) (Azizi & Bottaro, 2020).

3.3.5 Surface imprinting polymerization

Polymers from this method are created by applying imprinted layers onto porous silica particles (specifically, chromatographic grade) or solid mediums using various techniques. The simplicity and applicability of this approach make it suitable for various fields. The sorbents produced through this procedure exhibit several advantageous characteristics, including a significant imprinted surface area, precise control over their size and shape, and several binding sites. According to Farooq et al. (2018), this method has shown improvements in reproducibility, selectivity, and sensitivity. However, its potential for large-scale production is still limited.

3.3.6 Sol-gel polymerization

The process of sol-gel polymerization involves the utilization of organically modified silanes, leading to the formation of hybrid sol-gel materials. The polymerization technique employed in this study is considered environmentally sustainable due to the utilization of water or ethanol as solvents. This method is specifically employed for the synthesis of water-compatible MIPs within an aqueous environment while maintaining ambient temperature conditions. This method employed in the production of MIPs yields particles that possess an appropriate size, exhibit a highly porous structure, and demonstrate thermal stability and rigidity (Farooq et al., 2018).

3.4 Washing step

The washing stage in the preparation of MIPs is a critical step. After the polymerization of MIPs, the resulting materials are typically subjected to a washing process. This involves rinsing the polymers with appropriate solvents to remove any non-specifically bound molecules and residual template molecules (Shoravi et al., 2016). Washing can be done using soxhlet extraction, accelerated solvent extraction, or by shaking vigorously.

• Solvent selection for washing: The choice of solvent for the washing stage depends on several factors such as the solubility of the target molecules and the compatibility with the polymer matrix. Commonly used solvents include organic solvents (e.g. methanol and ethanol) or aqueous solutions with appropriate pH and composition (G. Liu et al., 2015).

• Optimization of washing conditions: The washing conditions, including the type and duration of washing, need to be optimized to ensure the efficient removal of unwanted molecules while maintaining the integrity and stability of the MIPs. Factors such as the binding affinity, polarity and stability of the target analytes and the polymer matrix should be considered (G. Sun et al., 2014).

• Washing effectiveness: The effectiveness of the washing stage in removing unbound molecules and template residues significantly impacts the performance of MIPs. Insufficient washing can result in template bleeding, leading to non-specific binding or interference in subsequent applications (Kryscio & Peppas, 2012).

3.5 Applications of MIPs

Molecularly imprinted polymers are frequently used in a diversity of ways (Tables 3 and 4). In the medical field, it is used as a tool for purification, tracing drug concentrations, and diagnostics, all of which are essential for regulating dosages to increase patient safety

Table 3. Application of MIPs for the extraction of pesticides

Matrix	MIP-Extraction	Quantification	Analyte	Recovery (%)	LOD (mg/L)	Reference
Grains	MIP-DSPE	HPLC-UV	Triazine	82.0–99.0	0.90–1.20	Geng et al. (2015)
Soil	MIP-SBME	GC-NPD	Monochrotophos	92.3	2.40 × 10^−2	Zhu et al. (2006)
River Water	MIP-SPE	HPLC	Chlorpyrifos	83.1	6.30×10^−3	Saad et al. (2021)
River Water	MIP-DSPE	GC-MS	Chlorpyrifos	107.3	3.000 × 10^−5	Teixeira et al. (2021)
Water	MIP-SPE	HPLC-UV	Diazinone	85.0	2.19	Karimian et al. 2017)
Water	MIP-DSPE	GC-ECD	Dicofol, DDT	82.6–100.4	0.12–0.26	Ndunda & Mizaikoff (2016)
Fruits	MIP-SPME	HPLC-UV	Diazinone	96.0–104.0	2.00 × 10–5	Bazmandegan-Shamili et al. (2016)
Orange	MIP-SBSE	HPLC	Triazine	33.0	0.23	Díaz-Álvarez & Martín-Esteban (2018)
Ginseng	MIP-SPE	GC-ECD	Organochlorine fungicides	79.3–92.3	1.00×10–3	Xu & Liang (2019)

Table 4. Fields of application of MIPs

Field	Example	Reference
Environmental Analysis	Removal of organic pollutants from water sources	Y. Huang et al. (2019)
	Detection and removal of heavy metals from wastewater	Ahmad et al. (2018); P. Han et al. (2020)
Pharmaceutical and Biomedical Applications	Drug delivery systems and controlled release	Haginka et al. (2001); He et al. (2021); Kalecki et al. (2020); K. Zhang et al. (2016)
	Selective extraction of active pharmaceutical ingredients (APIs)	Paul et al. (2017); Wang et al. (2021); Yang and Shen (2022)
Food and Beverage Analysis	Detection and quantification of food contaminants and toxins	Tarannum et al. (2020); Zhao et al. (2017)
	Selective extraction of flavor compounds from beverages	Cengiz et al. (2022)
Chemical Separation and Catalysis	Enantioselective separation of chiral compounds	da Silva et al. (2010)
	Catalytic applications in organic synthesis	Vargas-Berrones et al. (2023)
Sensor Technology and Diagnostics	Development of MIP-based sensors for rapid detection of analytes	(Banerjee et al. (2018)
	Application of MIPs in medical diagnostics and disease biomarker detection	Rajpal & Mishra (2022)

In a study conducted by S. Xu and Lu (2015), a molecularly imprinted polymer MIP was developed to selectively extract and preconcentrate dimethomorph, a morpholine fungicide, from ginseng samples. The dimethomorph molecularly imprinted polymer was synthesized through precipitation polymerization, employing butanone and n-heptane as porogens. The functional monomer utilized in this study was methacrylic acid (MAA). Following the implementation of molecular imprinted solid phase extraction (MISPE), the resultant samples exhibited enhanced purity, subsequently enabling the execution of gas chromatography analysis. The limit of detection (LOD) and limit of quantification (LOQ) for the technique were determined to be 0.002 mg/kg and 0.005 mg/kg, respectively. Recovery rates of dimethomorph commonly surpassed 90%. The method employed in this study was compared to other available methods for quantifying dimethomorph in ginseng. The results indicated several superior qualities of the method, including a lower LOQ and LOD, a wider linear range, improved repeatability, and enhanced reliability (Malik et al., 2019; S. Xu & Lu, 2015).

In the study conducted by Gao et al. (2011), a synthetic core-shell molecularly imprinted polymer was synthesized with high selectivity to eliminate traces of triclosan, an antibacterial and antifungal agent from environmental water samples. The synthesis methodology involved the integration of a sol-gel process utilizing silica-coated carbon nanotubes (CNTs) with a surface molecular imprinting technique. The methodology employed in this study was relatively uncomplicated, and multiple sets of molecularly imprinted polymers and non-imprinted polymers exhibited consistent and reliable results in terms of template binding. By employing water samples collected from rivers and lakes that were spiked with triclosan, this study successfully demonstrated the feasibility of detecting the presence of triclosan in samples that closely resemble realistic conditions. The recoveries of triclosan in river water and lake water samples, which were spiked with concentrations of 0.1, 0.3, and 0.5 g/L, exhibited recoveries in a range of 92.1% to 95.3% and 90.7% to 93.6%, respectively (Gao et al., 2011). Furthermore, experimental evidence has demonstrated that both MIPs and NIPs can be effectively reused for a minimum of ten additional cycles without experiencing any decline in their capacity.

Baghersad et al. (2022) synthesized a carbon composite using molecularly imprinted poly(methacrylic acid) (MIP-CC), a novel biosorbent for selectively removing the herbicide fenpiroxymate (Fen). In essence, functional monomers and cross-linkers were copolymerized with template molecules such as Fen to create MIPs. The manufactured MIP-CC was able to adsorb Fen to a maximum of 254 mg/g. The MIP-CC demonstrated superior selectivity against Fen and a better adsorption capacity as compared to the similar non-imprinted polymer (NIP-CC). High selectivity of MIPs is crucial for the target molecule during its synthesis.

Sulfonylurea herbicides are commonly employed to manage a wide range of broad-leaf weeds as well as certain grass species. Fang et al. (2021) synthesized magnetic molecularly imprinted polymers to analyze sulfonylurea herbicide. The utilization of iron oxide alone for pesticide extraction may lead to the formation of nanoparticle agglomerates. To address this issue, a vinyl-modified Fe₃O₄@SiO₂ nanomaterial was employed as the supporting matrix. In the study, bensulfuron-methyl (BSM) was used as the template molecule, methacrylic acid (MAA) was used as a functional monomer, trimethylolpropane trimethacrylate (TRIM) was used as a cross-linker, and azobisisobutyronitrile (AIBN) was employed as an initiator to synthesize the molecularly imprinted polymers. The MIPs demonstrated a high adsorption capacity of 37.32 mg/g, indicating their strong affinity and recognition specificity towards BSM. Additionally, these MIPs exhibited a rapid mass transfer rate and effective adsorption performance. The novel methodology exhibited a high degree of specificity in the separation and enrichment of sulfonylurea herbicide residues, thereby facilitating its application in the pre-treatment of multisulfonylurea herbicide residues.

Vanillin (3-methoxy-4-hydroxybenzaldehyde) is extensively employed as a vital aroma constituent in the food and cosmetic sectors, owing to its inherent vanilla fragrance. A diverse range of techniques is employed for the analysis of this chemical. Chromatographic techniques exhibit a notable level of selectivity and precision. However, the process of sample preparation is time-consuming and requires intricate initial procedures. Ji et al. (2014) developed a novel methodology aimed at augmenting the efficacy of the analysis of vanillin. A polystyrene MIP (PS-MIP) was synthesized by employing the swelling suspension polymerization technique with PS serving as the seed material. The authors provided an explanation regarding the comparative advantages of the PS-MIP concerning the MIP produced through bulk polymerization. They highlighted that the PS-MIP exhibited enhanced molecular recognition selectivity, increased adsorption capacity, and elevated binding capacity.

In a study conducted by Banerjee et al. (2018), a quartz crystal microbalance (QCM) sensor-based molecularly imprinted polymer was developed to detect 3-carene, a significant aromatic compound found in mango fruit (M. Indica L.). The selectivity of the sensor against the template analyte (3-carene) was assessed by comparing the MIP-modified sensor with the non-imprinted polymer. The investigation focused on examining the potential for volatile terpenes with similar structures to fit within the molecularly imprinted space. The sensor exhibited a selectivity of 90.9% towards 3-carene, whereas its selectivities towards α-pinene, ocimene, β-caryophyllene and furaneol were considerably lower at 2.9%, 2.6%, 2.2% and 1.3% respectively (Ghatak et al., 2018).

The process of food production, specifically roasting and drying has the potential to lead to the generation of methyl pyrazines. These compounds are recognized as significant taste and sensory constituents in numerous types of seeds and grains. In their study, Dela Cruz et al. (1999) developed a MIP through the process of photopolymerization. This involved the utilization of various templates, including 2,3,5-trimethylpyrazine (3MP) and 2,5-dimethylpyrazine (DMP), along with a monomer based on methyl methacrylate. Additionally, ethylene glycol dimethacrylate was employed as a cross-linker in the synthesis of the MIP. Based on their research outcomes, it was observed that the synthetic polymers exhibited a preference for the respective templates in the process of selectively extracting flavour characteristics during food processing procedures. Some applications of MIPs and the different extraction methods used for pesticide removal are listed in Table 3.

4. Challenges and limitations of MIPs for removal of pesticides

4.1 Inefficient removal of the template at the washing stage

Despite the MIP undergoing thorough washing, complete removal of the template proves to be a challenging task. This results in the leaching of the target analyte in real samples and subsequently leads to inaccurate results. This situation is made worse because comparatively larger amounts of templates are used in the preparation of polymer (in mg), while very little amounts of target analyte are found in environmental samples (usually ng). This problem can be solved by using the analyte’s structural analog as a template (Stevenson, 1999; W. Zhang et al., 2022) or removing the template by pressurized hot water extraction (Sarpong et al., 2019).

4.2 Extraction of water-soluble analytes

MIPs are designed to selectively bind target molecules based on their shape, size, and functional groups. However, their performance may be hindered when dealing with water-soluble compounds due to several factors (D.-L. Huang et al., 2015).

One major issue is that MIPs are typically prepared using organic solvents during the polymerization process. These organic solvents are not miscible with water, which makes it difficult to incorporate water-soluble analytes directly into the MIP synthesis. The hydrophilicity of the target analytes can pose challenges in terms of their proper interaction with the hydrophobic polymer matrix of MIPs.

Furthermore, the binding sites within MIPs are often optimized for non-polar or hydrophobic interactions. Water-soluble analytes, on the other hand, tend to form interactions with water molecules through hydrogen bonding or other polar interactions. The hydrophilic nature of water-soluble analytes may limit their compatibility with the hydrophobic binding sites within the MIPs, leading to reduced extraction efficiency.

To solve these issues, scientists have developed water-compatible MIPs by using the procedures described in subsequent chapters.

• Surface post-modification: Haginaka et al. (2001) modified their MIP by covering the surface first with a hydrophilic layer of glycerol monomethacrylate (GMMA), and then with glycerol dimethacrylate (GDMA). They employed a multi-step swelling and polymerization technique. From the outcome of the research, the modified polymer exhibited better adsorption recognition and decreased non-specific binding.

• Interfacial Pickering Emulsion Polymerization: The interfacial Pickering emulsion approach can be viewed as a strategy to lessen hydrophobicity and reduce the non-specific binding of target contaminants. Through the process of oil-in-water polymerization, template molecules are immobilized on the surface of MIP nanoparticles (Sarpong et al., 2019). To achieve selective identification and separation of a template peptide in an aqueous phase, L.-P. Zhang et al. (2017) used photo-initiated Pickering emulsion polymerization and interface-imprinting technology.

• Specially designed functional monomers: The utilization of specifically engineered functional monomers enables the formation of a matrix consisting of template-functional monomers in aqueous environments. The aforementioned phenomenon leads to the emergence of MIPs that demonstrate remarkable recognition abilities in aqueous environments (Zhong et al., 2014). Specifically designed polymers include 1-(α-methyl acrylate)-3-methylimidazolium bromide (1-MA-3MI-Br), 2-acrylamido-2-methyl-1-propane sulfonic acid, N, N’-diethyl(4-vinylphenyl) amidine and 1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-vinylphenylurea). Additionally, both modified and unmodified forms of cyclodextrins are also considered as specifically designed polymers (Sarpong et al., 2019).Wan et al. (2017) effectively produced a MIP through the utilization of Beta-cyclodextrin (β-CD) modified magnetic chitosan as the functional monomer, accompanied by the incorporation of methacrylic acid (MAA) as the assistant functional monomer.

• Hydrophilic functional monomers or co-monomers: One potential method to improve the synthesis of molecularly imprinted polymers for use in aqueous environments is by incorporating hydrophilic functional monomers. Methacrylamide (Urraca et al., 2006) and 2-hydroxyethyl methacrylate (HEMA) (Yan et al., 2009) are common hydrophilic monomers.

5. Conclusion and future research

In this review, all-inclusive notes have been given to various techniques employed in extracting pesticides in environmental samples before instrumental analysis. Synthesis procedures for MIPs, and the advantages and disadvantages of MIPs for the extraction of pesticides in environmental samples were discussed. In addition, an effort has also been made to condense the information regarding applications of MIPs. The review also show that the utilization of specifically engineered functional monomers and the use of additives to the MIPs enables the formation of a matrix consisting of template-functional monomers in recognizing and extracting target analytes. However, despite the MIPs having selective recognition of target analytes, setbacks such as incomplete removal of templates, and hydrophilicity of the target analytes limit their application in sample cleanup. These challenges can be ameliorated by using the analyte’s structural analog as a template or removing the template by pressurized hot water extraction. In addition, surface post-modification, interfacial pickering emulsion polymerization and the use of specially designed functional monomers are some measures that can be used to address some of the aforementioned setbacks.

Ethical statement

This article does not address analysis with ethical concerns.

Acknowledgements

The authors wish to thank the Chemistry Department, Kwame Nkrumah University of Science and Technology, Kumasi-Ghana for logistics support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data in this review can be obtained upon request from the corresponding author.

Additional information

Funding

This research did not receive any specific grant from any funding agencies.