Molecular imprinting: developments and applications in the analytical chemistry field

doi:10.1016/S0378-4347(00)00135-3

Journal of Chromatography B: Biomedical Sciences and Applications

Volume 745, Issue 1, 4 August 2000, Pages 3-13

https://doi.org/10.1016/S0378-4347(00)00135-3 Get rights and content

Abstract

In analytical separation science, molecularly imprinted polymers have been applied in several analytical techniques, such as liquid chromatography, capillary electrochromatography and capillary electrophoresis, solid phase extraction, immunoassay, and as a selective sorbent in chemical sensors. A benefit of imprinted polymers is the possibility to prepare sorbents with selectivity pre-determined for a particular substance, or group of structural analogues. The application most close to a wider acceptance is probably that of solid phase extraction for clean-up of environmental and biological samples. The improved selectivity of imprinted polymers compared with conventional sorbents may lead to cleaner chromatographic traces in the subsequent analytical separation. Furthermore, the solid phase extraction application does not suffer from drawbacks generally associated with imprinted polymers in chromatography, such as peak broadening and tailing. Most liquid chromatographic studies have focused on using imprinted polymers as chiral stationary phases for enantiomer separations. Also, the use of imprinted polymers as selective sorbents in capillary electrochromatography has been presented. For this purpose, a protocol to prepare superporous, monolithic imprinted polymer-based capillary columns has been developed. Due to the high affinities and selectivities often achievable, imprinted polymers have been considered as alternative binding entities in biosensors and in immunoassay type protocols. Here, high stability, easy preparation and ability to be used for assay of both aqueous and organic solvent based samples are advantages of the polymers.

Introduction

The incessant need for new fast and efficient methods within the pharmaceutical and environmental sectors fuel research into better and more selective and sensitive analytical procedures. The increasing number of analytes requires fast method development and the increasing number of analyses requires fast methods amenable to automation. Trace analytical methods for complex matrices rely on efficient sample enrichment and selective assays. In the research into new analytical techniques molecularly imprinted polymers (MIPs) have gained interest as a novel type of sorbent with attractive properties.

Imprinting of molecules occurs by the polymerisation of functional and cross-linking monomers in the presence of a templating ligand (Fig. 1) [1], [2], [3], [4], [5], [6], [7]. The template-monomer system is chosen such that in solution the imprint molecule complexes one or several functional monomers, which then become spatially fixed in a solid polymer by the polymerisation reaction. The resultant imprints possess a steric (size and shape) and chemical (spatial arrangement of complementary functionality) memory for the template. Following removal of the imprint molecules these imprints enable the polymer selectively to rebind the imprint molecule from a mixture. Two principally different approaches to molecular imprinting may be distinguished. The non-covalent, or self-assembly, approach where complex formation is the result of non-covalent or metal ion coordination interactions. The covalent, or pre-organised, approach which employs reversible covalent bonds, usually involving a prior chemical synthesis step to link the monomers to the template. Whereas it is generally perceived that non-covalent imprinting is more flexible in the range of chemical functionalities which can be targeted and thus the range of templates that can be used, covalent imprinting yields better defined and more homogenous binding sites. The former is also much easier practically, since complex formation occur on mixing template and monomers in solution prior to polymerisation. Recent years have seen an increasing number of studies into the use of selective MIPs in the analysis of drugs and pollutants in biological and environmental samples (for reviews see [8], [9], [10]). Imprinted polymers have been used in several analytical techniques, including liquid chromatography, capillary electrophoresis and capillary electrochromatography, solid phase extraction, ligand binding assay, and sensor technology. Since thorough discussions on each type of application can be found in the many excellent reviews cited throughout the text, in-depth presentations are beyond the scope of this review. Instead, the following discussion will concentrate on benefits and problems associated with the use of MIPs in analytical separations.

Section snippets

Solid phase extraction

The application of molecular imprinting in the analytical separation field most close to practical realisation is probably that of solid phase extraction, SPE. Several groups have already applied MIP-based solid phase extraction to biological and environmental samples and this technique may well be accepted generally in the not-to-distant future. The technique has variously been referred to as MIP-SPE or MISPE and has been reviewed recently [10], [11].

Following the first study on MIP-SPE

Preparation of imprints

A discussion on imprint preparation is beyond the scope of this overview, instead the reader is referred to the many excellent reviews published in recent years [1], [2], [3], [4], [5], [6], [7]. Some issues of particular interest for MIP applications in the analytical chemistry field have been discussed in a recent review [10]. The future is bound to see more of specialised development strategies for the optimisation of MIPs for each particular application area described above. Present issues

Conclusions and future outlook

The, at present, almost exponential growth in literature published each year is an indicator of the growing interest in molecular imprinting technology. In addition, molecular imprinting is now maturing from a phenomenon of interest to academics to a technique of potential practical interest to the analytical chemist. As an example, among the first to study the solid phase extraction application were several research groups within the pharmaceutical industry. This process will continue,

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Molecularly imprinted polymers (MIPs) are types of specific materials capable of recognizing and selecting compounds toward which they have been imprinted. This ability has made these materials increasingly popular in different areas e.g. for monitoring the content of harmful substances in various products, including water. In addition, many chemicals of various structures and applications are used as templates. The presented paper is a review that demonstrates knowledge and understanding of the molecularly imprinted polymers toward herbicides, with particular emphasis on the impact and needs to control their content, e.g. in plant parts, soils, or groundwater. This work focused especially on one of the newest herbicides used in large amounts, S-metolachlor, which is used in maize cultivation. It reviews the latest publications describing polymerizations in organic solvents and in water. Due to the much better solubility of pesticides in organic solvents, this type of polymerization is much more often described. However, due to the growing concern for the environment and the principles introduced in the so-called green chemistry, increasing emphasis should be placed on polymerization in an aqueous environment.
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In this study, a L-asparagine (L-Asn) imprinted membranes (L-Asn-MIPs) were synthesized via molecular imprinting for selective and efficient removal of L-Asn. The L-Asn-MIP membrane was prepared by using acrylamide (AAm) and hydroxyethyl methacrylate (HEMA) as a functional monomer and a comonomer, respectively. The membrane was characterized by scanning electron microscopy (SEM) and Fourier Transform infrared spectroscopy (FTIR). The L-Asn adsorption capacity of the membrane was investigated in detail. The maximum L-Asn adsorption capacity was determined as 408.2 mg/g at pH: 7.2, 24 °C. Determination of L-Asn binding behaviors of L-Asn-MIPs also shown with Scatchard analyses. The effect of pH on L-Asn adsorption onto the membrane and also the selectivity and reusability of the L-Asn-MIPs for L-Asn adsorption were determined through L-asparaginase (L-ASNase) enzyme activity measurements. The selectivity of the membrane was investigated by using two different ternary mixtures; L-glycine (L-Gly)/L-histidine (L-His)/L-Asn and L-tyrosin (L-Tyr)/L-cystein(L-Cys)/L-Asn. The obtained results showed that the L-Asn-MIP membranes have a high selectivity towards L-Asn.
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Molecularly imprinted polymeric materials demonstrated a huge potential to replace several natural product–based molecules in a wide range of applications, for instance, in diagnostic assays, small as well as (bio)macromolecular separation method, in biosensors, etc. Despite all the success with regards to research publications, a much broader applicability on the industrial scale is still fervently awaited on account of several reasons. However, with proper tuning of the monomeric units, physical conditions, and templating materials, it is certainly plausible to overcome the barriers associated with the commercialization of these novel materials. Therefore, in this chapter, various possibilities along with some thought-provoking success stories are discussed which will prove to be instrumental while implementing the materials in real world. Furthermore, a strategy to detect new SARS Coronavirus-2 on the imprinted-surfaces by making use of different polymer-coated nanoparticles has also been examined.
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Science and technology are working toward developing materials that can imitate molecular recognition–based activities present in life. Molecular imprinting is a technique that solves this problem by imparting polymeric materials with antibody-like recognition properties. Many of the practical issues traditionally associated with molecularly imprinted polymers (MIPs), such as difficulties in imprinting proteins, poor compatibility with aqueous environments, template leakage, and the presence of heterogeneous populations of binding sites in the polymers that contribute to high levels of nonspecific reactivity, have recently seen significant progress. This development is linked to a technologically driven transition in MIP research from bulk polymer to nanomaterial forms. The purpose of this chapter is to shed light on recent advancements in this sector and to provide a critical analysis of the current state of patents in the field as well as its commercialization possibilities.
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Molecularly imprinted polymers (MIPs) are considered as an analytical tool for trace level detection of template molecules from aqueous or real samples. The performance of MIPs plays a role of key prominence in its effective application. Numerous parameters affect the performance of MIPs, like solvent nature and volume, pH, appropriate ratio of monomer and template, temperature, and ability to form molecule-specific recognition sites within the host, operation time, etc. But removing the template into the polymeric cage is a critical step in the preparation of effective MIPs. While the removal of the template by any method creates many problems such as rupture and collapse of the cavity, inappropriate removal of the template (low binding site will be available), distortion of the cavity, adequate removal. During analytical application of MIPs, if template bleeding occurs the detection may be erroneous. Furthermore, aggregation of the template in the polymerization solution, aggregation of the imprinting-induced site, and deformation of the cavity by the relaxation of the gel decreases the efficiency of MIPs. This chapter aims to provide different parameters that can be expected to provide effective methods helpful for providing rational approaches for template removal from synthesized MIPs. The inefficient removal of templates may act as a major drawback to preparing MIPs.
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Citation Excerpt :
They form a three-dimensional polymer matrix with selective binding sites around the target molecule and create a platform that highly matches with stereochemical structure and functional groups of it. Already, various strategies for MIPs construction have been researched, such as chemical sensing [23], analytical separation, micro-extraction methods [24]. Since that MIPs are more acceptable for low molecular weight templates (MW＜1000), imprinting them for bio-macromolecules such as proteins, enzymes, etc., is a challenge [25].
In this study, the attempt has been made in the direction to design a new artificial receptor biosensor by use of a hybrid method of molecularly imprinted polymer (MIP) and aptamers (Apt) to ultra-trace Trypsin (Trp) enzyme recognition. Firstly, the effective surface of the electrode was increased by NiO nanoparticles electrochemical deposition. Then a prepared complex containing Apt-Trp was incubated on the NiO surface. A specific surface of Trp bind to one aptamer tail-end. The other tail of the aptamer was attached to NiONP from the NH₂ side and in this treatment, the protein target was immobilized as the template. The electropolymerization process was performed using dopamine to completely form a polymeric matrix around the target protein. Finally, the Trp molecule was eliminated with suitable eluent, and the prepared Apt-2DMIP biosensor was used for analytical experiments. This real-time detective sensor had unparalleled selectivity and sensitivity in the presence of off-target species to the Trp. A good diagnostic linear range from 1to 90 pg.mL⁻¹ was obtained with a detection limit of 0.75 pg.mL⁻¹. The imprinting factor was calculated without and in the presence of aptamer, and the results showed that aptamer significantly increased the throughput of the biosensor. Finally, in real samples including blood human serum and urine samples, the efficiency of the biosensor was evaluated, and satisfactory results were obtained.

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ReviewMolecular imprinting: developments and applications in the analytical chemistry field

Abstract

Introduction

Section snippets

Solid phase extraction

Preparation of imprints

Conclusions and future outlook

Trends Anal. Chem.

J. Chromatogr. B

J. Chromatogr. B

J. Pharm. Biomed. Anal.

Trends Anal. Chem.

Microchem. J.

Anal. Chim. Acta

J. Chromatogr. A

J. Chromatogr. A

Tetrahedron: Assymetry

J. Chromatogr. A

J. Chromatogr. A

J. Chromatogr. A

J. Chromatogr. A

J. Chromatogr. A

J. Chromatogr. A

React. Polym.

J. Chromatogr. A

Anal. Chim. Acta

J. Chromatogr. A

J. Chromatogr. A

J. Chromatogr. A

J. Chromatogr. A

J. Chromatogr. A

J. Pharm. Biomed. Anal.

Chem. Biol.

Angew. Chem. Int. Ed. Engl.

Adv. Polym. Sci.

Bio/Technology

Chirality

Clin. Chem.

Drug development assay approaches including molecular imprinting and biomarkers

Anal. Commun.

Anal. Chem.

Anal. Commun.

Anal. Commun.

Drug development assay approaches including molecular imprinting and biomarkers

Drug development assay approaches including molecular imprinting and biomarkers

Anal. Chem.

Anal. Chem.

Anal. Chem.

Chromatographia

Review
Molecular imprinting: developments and applications in the analytical chemistry field