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The application and development of Molecular imprinting technologyAbstract: Molecular imprinting is a newly developed methodology which provides molecular assemblies of desired structures and properties and is being increasingly used for several applications such as in separation processes,microreactors, immunoassays and antibodymimics, catalysis, articial enzymes, biosensor recognition elements and bio- and chemo-sensors. In this paper,the auther introductived the Molecular imprinting technology and its application. The theory of Molecular imprinting polymers is also reviewed in this paper. Finally,the auther presented the problems and challenges in molecular imprinting .Key words: Molecular imprinting; Molecular recognition;Application and development ;1.IntroductionMolecular recognition is dened as the ability of one molecule to attach to another molecule that has a complementary shape1.The incentive to develop materials that bind other molecules selec-tively comes from the tremendous medical and technological signi-ficance of molecular recognition in applications that include affinit-y separations,medical diagnostics,drug delivery,chemical and boilog-ical sensors, and catalysis. Molecular imprinting can be envisaged as the selective manipulat-on of the shape, size and chemical functionality of a polymermatr-ix by a templatemolecule.The imprinting process consists of the po-lymerisation of functional monomers in the presence of a template species or a molecule closely related to the template species.The p-oymerisation is conducted in a solvent (porogen) which facilities thefomation of templatemonomer complexes by stabilisation of inter-actions.These complexes are then xed into this spatial arrangementby the inclusion of a high proportion of cross-linking monomer, which imparts rigidity to the polymer network.Removal of the tem-plate species affords nano-cavites,which are complementary in size,shape and chemical functionality to the templated species. These ca-vities have the ability to selectively rebind the template.The generalpriniples,areas of applications and limitations of imprinted polymershave been extensively reviewed 26.2.The application of molecular imprinting7The concept of molecular imprinting based on molecular interaction is very old but their applications in various elds are emerging ecently particularly for sensor applications.The initial examples of molecular imprinting by use of synthetic organic polymers were independently reported by Kiefer et al. (1972) and Wulff and Sarhan (1972) and have since then found applications in separation processes (chromatography, capillary electrophoresis, solid phase extraction (SPE), membrane separations), microreactors,immunoassays and antibody mimics, catalysis and articial enzymes, biosensor recognition elements and bio- and chemo-sensors. The eld of molecularly imprinted polymers (MIPs) will evolve further to include new applications such as recognition elements in intelligent drug delivery devices, in targeted drug delivery applications and in microuidics devices with applications as analyte sensing microvalves and microactuators. Themolecular imprinting technique can be applied to different kinds of target molecules, ranging from small organic molecules to polypeptides, high molecular proteins and even whole cells.3. The principle of molecular imprintingThe principle of molecular imprinting is shown in Fig. 1. Generally, the fabrication of MIPs consists of three main steps (i) pre-arrangement of the monomers around the target molecule, (ii) polymerization in the presence of cross-linker and (iii) removal of the target molecule by extraction process.These MIPs can be stable in various critical chemical and physical conditions for a long time and reused without any alteration to the memory of the template. Usually MIPs have been prepared in the form of a macroporous monolith, then ground and sieved to the required particle dimensions. Recent improvements in the morphology of MIP particles have been achieved using a precipitation polymerization procedure that allows to obtainmicro- or nanospheres with regular size and shape and particularly able to rebind effectively template molecule due to the high surface/volume ratio. The use of imprinted lms in sensor development has attracted a lot of interest recently because of faster rate of diffusion through surface and resulting into high sensitivity. Imprinted lms also possess high physical and chemical stability with respect to immobilized biomaterials as the recognition part. Bulk imprinted polymers have been employed in sensors as porous materials. But this design suffered from long diffusion times of the target molecule into the polymer. In recent years, several groups have dealt with the application of imprinted lms as recognition layers applied on various transduction systems for example, piezoelectric,amperometric,surface plasmon resonance, uorimetric and eld effect transistors. These imprinted lms can be in situ synthesized at an electrode surface by electropolymerization or at a non-conducting surface by chemical grafting or in sandwich conguration.3. Problems and challenges in molecular imprintingCompared with antibodies, enzymes or biologicals receptors,mole-cularly imprinted materials possess inherent advantages viz.robustne-ss,low cost and potential utility in cases where norecognizing biom-olecule is available. Besides many advantages,molecular imprinting technology still needs to overcome few limitations such as templateleakage, poor accessibility of the binding sites, low binding capacityand non-specic binding. Since biological recognition mainly occursin aqueous systems,it is quite important to make MIPs capable of recognition in water in order to mimic biomolecules. The develop-ment of a method for making efcient MIPs in pola organic solve-nts is of general interest.The applicationsof imprinted polymers are also restricted to the use of organic solvents for the dissolution of organic polymers viz. acrylate or acrylic type polymers which are most commonly used for the preparation of MIPs. Template molec-ules that are only soluble in aqueous phases are generally not ame-nable to imprinting in such amanner. Imprinting of larger moleculeslike polypeptides and proteinsis still a challenge requires well-denedprotocols. The hydrophobicnature and highly cross-linked structure of the polymer limits the access of the imprinting binding sites by the large proteins. The molecular imprinting of enzymes is also lesspractical, because of requirement of aqueous buffer for the biologic-al activity of the enzymees. The preparation of MIPs in aqueous s-ystem is very challenging task because of the interference of water molecules.Non-specic interactions between the template and functi-onal monomers or functional oligomers or polymers may also beco-me much weaker or even disappear in aqueous system. Further, m-any biomol-ecules are often insoluble or loss activities in organic solvents. Thus, it is of great importance to develop imprinted mate-rials that can be used in aqueous environment.Resear-ch is going on to overcome these limitations and thrust is to nd out new pol-ymeric matrix for molecular imprinting that can be usedfor environ-mental and biological applications. Solgel imprinting is also one ofnew emerging eld in area
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