September 5, 2007
Biomimetic Sensors for Toxic Pesticides and Inorganics Based on Optoelectronic/Electrochemical Transducers-An Overview
By Rao, T Prasada Prasad, K; Kala, R; Gladis, J Mary
Toxic pesticides and heavy metals constitute an important class of pollutants that degrade the environment due to their persistent nature and their unavoidable use in increasing the agricultural output and industrial importance respectively. The design and development of portable devices such as sensors rather than laboratory based instruments in monitoring the above species at trace levels in real samples is prime challenge to analytical chemists at this juncture. Because of the poor physical and chemical stability of biosensors despite their specificity and sensitivity preclude their use in environmental analysis. On the other hand, in conventional chemical sensors are beset with problems of selectivity. Molecularly imprinted polymers (MIPs) are being increasingly used as recognition elements in mimicking molecular/ ionic recognition by natural receptors. A brief survey of synthetic strategies and characterization of MIPs, transducers that convert binding event into a detectable signal, integration strategies of recognition element with a suitable transducer and finally the reported sensors for toxic pesticides and inorganics is discussed. Future outlook of such biomimetic sensors in environmental analysis has been highlighted. Keywords molecular imprinting, pesticides, inorganics, sensorsINTRODUCTION
Man and technology are inseparable parts of modern civilization. In order that technological advances make minimum impact on biosphere, it has become necessary to take adequate steps to cleanse the environment and check its further pollution through various control measures. In executing these control measures, it has become necessary to identify and assess the extent of pollution in order to determine the type and degree of treatment required to render the waste harmless.
The classification of trace metals as nutrients/toxic is in a state of change. The toxic and essential elements are no longer separated into two rigid categories. It is now recognized that all metals will exert toxic effects when present in excess and certain toxic metals, so classed because of adverse effects at relatively small doses, may be fulfilling some essential function at more minute concentrations (1).
As a result of changing and extending the use patterns of pesticides and ongoing product development, several trends can be observed in pesticide science. For example, there has been a clear shift from the use of "long-life" persistent insecticides such as organochlorine compounds to more polar and readily degradable "short- life" pesticides such as N-methyl carbamate pesticides. Other major trends are the extensive use of "traditional" herbicides eg. triazines, chlorophenoxy acids and polyureas and so called "modern" herbicides eg. sulphonyl ureas and imidazolinones, with favourable properties such as a low dose rate of application and a high degree of (bio)degradation (2). Long-life pesticides, though banned in few countries are still in use in other countries in the world.
Table 1 lists the maximum permissible concentrations, potential health effects and common sources of contamination for selected toxic inorganics and pesticides. It is hard to imagine a more topical subject than toxic pesticides/inorganics in view of almost daily references to the dangers of one or other of them in environment.
Advances in analytical instrumentation and their subsequent application in developing refined, sensitive, selective and accurate techniques for trace toxic species have made yesterday's esoteric investigations today's routine analyses. As a consequence, the normal concentrations in environmental samples and what may be toxic are becoming more clearly delineated. Thus, the requirements of analytical technologies for monitoring environment ranging from threats such as occupational health and safety risks, to chemical warfare prompted the researchers to design a host of miniaturized analytical instruments for field studies rather than elaborate laboratory based instruments. Sensor devices fit very well in this changing scenario. The poor physical and chemical stability of biosensors, despite their specificity and sensitivity, preclude their use in environmental analysis. On the other hand, chemical sensors are beset with problems of selectivity. Molecular imprinted polymers (MIPs) are being increasingly used as recognition elements in mimicking molecular/ionic recognition by natural receptors.
We direct the reader to the articles (3-14) listed in Table 2 for reviews on MIP based sensors. As a starting point to understand the basic concepts of "Molecular Imprinting", one can refer to a tutorial lecture of Haupt (15).
THE REVIEW: GOALS AND CONTENT
As seen from Table 2, the reviews by Vidyasankar and Arnold (3), Dickert and Hayden (4, 5) Ensing and de Boer (6) and Haupt and Mosbach (7) dwells on the early developments of MIP based sensors during the period of 1995-2000. Other review articles mentioned in Table 2 concern with electrochemical (8-11)/optical (12-14) sensors based on Molecular Imprinting. However, there is no concerted effort to review the developments in design and development of sensor devices for the quantification of toxic pesticides and heavy metals and uranium which assume distinct importance as mentioned above. It is pertinent to mention here the two review articles by Zolotov (16) and by our group (17) on ion imprinted polymer-solid phase extraction for preconcentrative separation of organic/ inorganic pollutants. Hence, this review deals with the analytical methodologies developed for the determination of traces of toxic pesticides/inorganics using biomimetic sensors as of today. We earnestly hope this review and two articles Zolotov et al. and Prasada Rao et al. (16, 17) enthuse analytical chemists to gauze the potential of "Molecular Imprinting Technology" in undertaking this exciting area which has immense scope in environmental science i.e. either in detection/removal of toxic pesticides/inorganics. Hence, we tried to give bird's eye view of various strategies for synthesis and characterization of molecularly imprinted polymer recognition elements, transducers, employed to convert binding event into a detectable signal and integration of recognition element with transducer in addition to describing various biomimetic sensors developed for toxic pesticides and inorganics.
SYNTHETIC STRATEGIES FOR MIPs
Polymers with high affinity binding sites and selectivity can be produced by carefully optimizing the polymerization conditions that will stabilize the template-monomer complexes. The experimental variables include the type and relative amount of imprint molecule/ ion, functional monomer and crosslinking agent, porogen used for imprinting, initiator and rebinding of the analyte, polymerization temperature and pressure. Various commonly employed imprinting strategies to introduce size and shape specific recognition sites into cross-linked polymers are described below.
Covalent or Stoichiometric Non-Covalent Imprinting
The covalent or pre-organized approach was primarily developed by Wulff and his coworkers (18) which employ strong, reversible covalent bonds usually involving a prior chemical synthesis step to link the monomers to the template (See Fig. 1 ) After polymerization, the imprinting molecule can be removed only by chemical cleavage. When covalent interactions are used, the binding site monomers can be employed in the exact stoichiometric ratio to the template molecule resulting in homogenous and higher binding constants resulting in most efficient catalytic systems. It is important to remark that the functional groups in the imprinted cavities are located on different polymer chain segments, which are held in definite mutual orientation simply by cross-links (reminiscent of the structure of active centres of enzymes).
Noncovalent or Self Assembly Imprinting
Noncovalent or self assembly approach was pioneered by Mosbach and coworkers (19). This involves host-guest complexes produced from weak intermolecular interactions (such as ionic or hydrophobic interactions, hydrogen bonding, van der Waals forces, pi - pi bonds and metal coordinations) between analyte and monomer precursors. These self-assembled complexes are spontaneously established in the liquid phase and are then sterically fixed by free radical polymerization with a cross-linking monomer. After template extraction, various recognition sites that are specific to print molecule are established (See Fig. 2). The range of templates that can be used are wide and easier but results in heterogeneity.
Semicovalent or Sacrificial Spacer Imprinting
This is a hybrid imprinting strategy proposed by Whitcombe et al. (20, 21) that comprise a covalent imprinting step and subsequent rebinding by noncovalent interactions. This strategy was used for molecules with few functional groups and for one capable of creating recognition sites for templates carrying single or multiple spatially separated groups.
In 1 992, Takagi's group (22) proposed a new imprinting technique based on oil-in-water (o/w) emulsion named as "Surface Imprinting." In 1994, Goto's group (23) have developed a similar technique but with water-in-oil (w/o) emulsion. Schematic diagram of latter technique of surface template polymerization with w/o emulsions is shown in Fig. 3. In both the techniques, the MIPs are prepared by emulsion using a functional host molecule, an emulsion stabilizer, a polymer matrix forming a monomer and a print molecule. The functional host molecule, which is amphiphilic in nature, forms a complex with a print molecule during emulsion. Thus, the formed complex remains at the reaction surface. The organic phase containing the cross-linking agent is polymerized so that target selective cavities are created on the polymer surfaces, not inside the polymer matrix unlike covalent/non-covalent imprinting techniques. Thus, surface imprinting techniques offer faster rebinding kinetics and can handle water soluble templates such as metal ions and biological components.
Surface Imprinting on Inorganic Supports
In this, the print molecule is allowed to form adducts with functional monomers in solution and the formed complexes are subsequently allowed to bind to active inorganic supports such as silica wafers (24) quartz crystal (25) or titanium dioxide (26). Fig. 4 shows a typical surface imprinting process of precoated quartz crystal microbalances with dual electrode structures.
Imprinting by Sol-gel Technique
Templated sol-gel glasses has been prepared using organoalkoxysilanes. In one approach, organoalkoxysilanes, chosen for their affinity towards a template molecule, are combined with tetramethoxysilane to form a hybrid composite (27). In another approach, the template can be covalently attached to inorganic framework for e.g., a silicon alkoxide derivatized template can be coupled with tetramethoxysilane to form the cross-linked network (28).
The print molecule is first immobilized on the surface of a porous silica mould prior to polymerization. Subsequent dissolution of silica results in a "mirror image" pore system containing binding sites uniquely residing at the surface. The above imprinting process is known as Hierarchial templated synthesis (29, 30) (See Fig. 5).
Heirachial Double Imprinting
Dai's group (31, 32) has synthesized novel materials with heirarchial structures based on double imprinting methodology (See Fig. 6). On the microporous level (1-3 [Angstrom]), metal ions served as template. On the mesoporous level (diameters of 25-40 [Angstrom]) micellar structures produced by self assembly of surfactant molecules were used as templates. Removal of both metal ions and surfactant micelles resulted in the formation of imprints with different sizes within the silica matrix, each with a specific function.
Molecular imprinted polymers generally prepared by extensive crosslinking polymerization in the presence of template molecules, are obtained as rigid, insoluble, solid materials with frozen binding sites complementary to the template molecules. Understanding the physical basis of enzymes viz. solubility in aqueous media, preserving defined globular conformations in solution, and preparing the synthetic materials is of great interest to synthetic chemists. In recent years, a class of novel aqueous swellable polymers (hydrogels) has been synthesized which can respond to environmental changes and amplify them in the form of phase transitions (33). These gels are called "responsive" or "smart" gels and have been used to prepare artificial muscles, actuators, controlled release systems, sensors, optical shutters etc.
Ion Imprinting by Template Embedding
The first example of this method of imprinting was reported by Nishide and coworkers (34), who polymerized metal complex of 1- vinyl imidazole with 1-vinyl-2-pyrollidone and divinyl benzene. More recently, Lemaire and coworkers (35), Murray's group (36) and Say's group (37) have adopted this approach for selective separation of lanthanides, actinides and transition metal ions, respectively.
Ion Imprinting by Trapping
Prasada Rao and his coworkers have prepared lanthanide/ actinide/ noble metal IIP particles by single pot polymer synthesis by copolymerizing mixed ligand ternary complex (metal-chelating ligand- vinylated ligand) with styrene/HEMA/MAA (monomer), divinyl benzene/ EGDMA (cross-linking monomer) in presence of 2,2'-azobis- isobutyronitrile (initiator). The imprint ion is selectively leached with mineral acid, while the chelate ligand is trapped in the polymer matrix. This allows selective rebinding of template ion from dilute aqueous solutions resulting in preconcentrative separation (38, 39).
CHARACTERISATION OF MIPs
The direct evidence for the formation of noncovalent monomer- template interactions can be studied by traditional spectroscopic techniques like NMR, CHN-analysis, FT-IR, UV-Visible or fluorimetric techniques. On the other hand, the study of MIP-template interactions is rather difficult on account of the fact that MIPs are insoluble and intractable. Hence, these MIPs cannot be characterized by more commonly employed polymerization characterization methods that would require polymer solutions e.g., gel permeation chromatography, solution NMR techniques and UV measurements. Furthermore, since MIPs are amorphous, crystallographic or microscopic methods cannot be used to determine the structure of the MIP binding sites, although microscopy has aided the macroscopic understanding of MIP morphology (40, 41). Therefore, there are only a limited number of direct physical characterization methods for imprinted polymers. Cormack and Elorza (42) have briefly listed various morphological and chemical characterization methods that can possibly find use in MIP characterization. We now present a brief outline of various characterization techniques employed by MIP researchers with appropriate recent citations.
The morphology of MIPs can be probed in the same way as that of the porous solids. Depending on the characterization technique, useful information can be deduced regarding pore volumes, pore diameter, pore size distribution and BET surface areas of the materials.
Water Uptake. Macroporous polymers are predominantly porous even in the dry state and uptake experiments can estimate the specific pore volume. Even though water uptake of PVC with various plasticizers is available, the corresponding data for MIPs are not available.
Swelling Ratio. Yoshida et al. (43) and Kala et al. (44) have evaluated the rigidity of the surface imprinted and erbium(III) IIPs synthesized by gamma-irradiation by swelling ratio experiments with toluene by soaking for 30 minutes. These researchers have successfully correlated the swelling ratio values of IIPs formed by using different functional and crosslinking monomers with imprinting effect, percent extraction, equilibrium loading and selectivity coefficients.
Surface Area and Porosity. N^sub 2^ sorption porosimetry has been used for obtaining BET surface area, specific pore volume, average pore diameter and pore size distribution by measuring the amount of gas sorbed as a function of pressure, constructing sorption isotherms and application of BET theory and mathematical models. Karrison et al. (45), Biju et al. (46) and Daniel et al. (47) have employed this technique to distinguish the MIPs based on pore size as microporous, mesoporous or macroporous. Sellergren and Shea (48) have studied the effect of porogens on surface area, pore volume and size of MIPs.
Relative Dielectric Constant. The relative dielectric constant of the plasticizer added to PVC while the forming membrane has significant influence on subsequent membrane sensor performance using potentiometry. Prasad et al. (49) have shown that the use of plasticizer with high dielectric constant gave Nernstian response over a wider range in case of dysprosium(III) IIP potentioselectrode as observed in the case of lanthanum(III) conventional ion selective electrode (50).
Microscopy (SEM/TEM/AFM). Optical microscopy can be used to verify the structural integrity of MIP beads and SEM/TEM/AFM can often image the surface morphology and correlate to the selective rebinding of the template. Gonzalez et al. (51) have employed SEM as a tool for studying the surface morphology of MIPs by altering the functional monomer, porogen or the volume of the latter during MIP synthesis. Ye et al. (52) and Yoshida et al. (53) have characterized molecularly imprinted microspheres and surface imprinted polymer materials using SEM. Perez-Moral and Mayes (54) and Daniel et al. (55) have characterized propanolol- and palladium(II)-imprinted polymer particles prepared by different polymerization methods using SEM. Same technique is used for characterization of polymer membranes prepared by embedding of UO^sup 2+^^sub 2^-vinyl benzoate in an ionically permeable membrane (56) and zinc(II) surface imprinted membrane (57). Koenig and Chechick (58) have employed TEM to characterize polymerizable gold nanoparticles embedded into macroporous cross-linked polymers. AFM has been employed to characterize the molecularly imprinted composites for the first time by Hilal et al. (59).
The chemical characterization methods that can be used for solid samples can also find application in characterizing solid MIPs.
Elemental Microanalysis. Elemental microanalysis has been used to calculate the comonomer composition of the polymer and has been advantageously utilized by Lemaire's group (60) and our group (61) while characterizing gadolinium(III) and palladium(II) IIP resins/ particles, respectively.
FTIR. The investigations of MIPs by FTIR spectroscopy are simpler with solid polymers than with a mixture of monomers in solution. Indeed solid polymers can be used directly, without other constituents, which do not interfere with the determination of polymer functionalities. Kobayashi et al. (62), Shea et al. (63), Lu et al. (64), Oral and Peppas (65) and our group (47, 61) have characterized imprinted polymers synthesized by different strategies using FT-IR spectra. Solid-State NMR. Solid-state NMR was used to determine the polymerization yield and also to verify if the template molecule was still bound to the polymer after MIP synthesis (66). However, it was not possible to determine the presence of selective cavities with this experiment. Sasaki and Alam (67) examined the binding sites in an imprinted silica xerogels by using ^sup 31^P MAS NMR. MIPs prepared by phase inversion (which are not cross-linked) are not completely insoluble in some solvents and facilitate their characterization by proton NMR (68).
Energy Dispersive X-ray Spectroscopy (EDS). Gladis and Rao (69) have characterized uranyl IIP particles by EDS in ascertaining the complete removal of uranyl imprint ion and trapping of non- vinylated ligand viz. 5,7-dichloroquinoline-8-ol during leaching with 6M HCl.(See Fig. 7)
Thermogravimetric (TGA) and Differential Thermal (DTA) Analysis. TGA/DTA studies were conducted by our group to characterize the unleached and leached imprinted polymer particles to prove that non- vinylated ligand viz. 5,7-dichloroquinoline-8-ol is intact even after leaching with mineral acid (70). (See Fig. 8)
X-ray Diffraction (XRD). The complete leaching of lanthanide/ actinide/noble metal imprint ion on treatment with mineral acid was established by our group by comparing X-ray diffractograms of unleached and leached IIP particles with ternary complex of imprint ion (61,71,72). (See Fig. 9 for palladium IIP particles(61) ). However, this method is not that sensitive to establish quantitative leaching of imprint ion.
UV-Visible Spectroscopy. As mentioned earlier, UV-visible spectra of solid IIP is not that sensitive unlike solution studies. However, the analysis of leachant solutions and from the blank values obtained during enrichment experiments using UV-Visible spectroscopy offer conclusive proof for complete leaching of particular inorganic imprint ion (47, 71, 72).
TRANDUCERS FOR MIP SENSORS
Various optoelectronic and electrochemical transducers that can be employed to convert a binding event into a detectable signal are shown in Chart 1. Bianco-Lopez et al. (10) in 2004 have reviewed the electrochemical transduction techniques while designing MIP-based sensors. We now review the optoelectronic transducers, viz. fluorimetrie, UV-Visible, FT-IR, surface plasmon resonance and chemiluminescence.
Fluorimetry is perhaps the most sensitive optically based measurement technique and is capable of yielding very low detection limits (
Cooper et al. (77) report the utilization of two novel fluorescent functional monomers in EGDMA based MIPs. Murray et al. (78) have further extended the scope of MIP based sensors by developing a fluorescent transducer based lead(III) sensor based on formation of fluorescent complex with binding of imprint ion. In a similar vein, Murray and coworkers (79, 80) have developed fluorescent transducer based optical sensors for chemical warfare agents or rather their hydrolysis products based on interaction of ancillary ligand with fluorescent metal complexes within the MIP. Subsequently, Dickert et al. (81) have created urethane-based MIPs for the detection of polycyclic aromatic hydrocarbons. Turkewitsch et al (82) have prepared fluorescent transducer based MIP sensor based on the quenching of functional monomer fluorescence upon binding of analyte. Haupt et al. (83) have devised a fluoroimmunoassay procedure for the herbicide, 2,4-D based on MIPs.
Kunitake and coworkers (84) have developed devices that allow the confirmation of optical observation, i.e., by colorimetrie detection of solvent vapours using MIPs deposited on quartz crystals, using extremely sensitive independent mass-sensitive measurements.
The first demonstration of the use of MIPs in optical transducer based sensors was the work of Andersson et al. (85) using ellipsometry to quantify the amount of vitamin K bound in a monolayer of octadecylsilane supported on a silicon wafer.
Surface Plasmon Resonance (SPR)
SPR is a technique somewhat akin to ellipsometry, whereby the binding of organic molecules to a surface results in a change in the angle of incident light. Lai et al. (86) prepared MIP against theophylline, caffeine and xanthine and deposited these on silver- coated glass substrates. This is the first report that uses SPR to detect the binding of substrates to MIPs.
The detection of light emitted from the biochemical degradation of a compound has the advantage that it requires neither an excitation source, as in fluorescence, nor a monochromator or an optical filter for the detection of resulting signal. Because the intensity of the emitted light is directly proportional to the concentration of analyte present, chemiluminescence is a very attractive detection technique for the study of MIP materials during rebinding. Haupt made an attempt to develop a chemiluminescent adsorbent assay for the detection of 2,4-D using non-related probes for competitive binding detection (87). More recently, Zhou et al. (88) prepared a flow-through sensor for the determination of chenbuterol in urine based on chemiluminescence transducer(See Fig. 10). Lin and Yamada (89) investigated the potential to prepare MIP sensor for 1,10-phenanthroline based on the decomposition of H^sub 2^O^sub 2^ with a ternary complex catalyst viz. Cu(II)-1,10- phenanthroline-4-vinylpyridine employing chemiluminescence transducer.
Jakush et al. (91) have developed a MIP sensor with IR transducer for 2,4-D by immobilizing MIP onto zinc selenide attenuated total refraction elements. Thick films (~5 mm) were immobilized onto the surface of transducers and upon exposure to test solutions, selective enrichment of the analyte in MIP layer was measured by observing mid-IR bands at 1595 and 1410 cm^sup -1^, assigned to the anionic form of the carboxyl groups. Consequently, the approach could be very attractive for the continuous monitoring of pollution in water.
Quartz Crystal Microbalance (QCM)
Zhang et al. (92) developed MIP sensor with QCM transducer (see Fig. 11 for schematic diagram) by modifying piezoelectric quartz crystal with MIP membrane. For formation of MIP membrane, the MIP particles were suspended in 10 ml of tetrahydrofuran dissolving 5 mg of Polyvinylchloride powder in it. About 10 [mu]l of the suspension was spread onto the centre of the quartz crystal surface resulting in formation of thin membrane at room temperature. The sensor was coated with homogenous membrane of polymer by repeating the coating for 3 times.
IMMOBILIZATION/INTEGRATION OF MIPS WITH TRANSDUCERS
There is no doubt that polymers that display higher selectivity for a given analyte can be synthesized via MIPs. For use in sensors, however, one of the fundamental difficulties is combining the recognition element with a suitable transducer, in order to convert the binding event into a detectable signal. The pictorial representation of MIP sensor is given in Figure 12.
In-situ polymerization is the best immobilization procedure and consists of in situ synthesis of MIPs at the transducer surface and has the advantage of integrating the immobilization step into an automatic mass-production process.
Spin or spray coating is another method of immobilizing MIPs as film onto a transducer surface. This strategy is more often employed todate. In any case, the control of layer thickness is necessary to adapt sensor response time and sensitivity. In general, three dimensional networks are preferred to two dimensional because they are more stable and more favourable for anchoring the molecule at several points. The affinities for the polymer are higher, although at the cost of a slower response, so thickness-response time must be in compromise. Manual deposition of a MIP layer is also used on various occasions.
Entrapment/dispersion of MIP particles into gels (93) membranes (94) is another approach of integrating MIPs with transducers. These prepared materials are applied onto the transducer surface. An inert soluble polymer such as PVC entraps the MIP particles. For sensing layers using particulate MIP, the sensor response time is closely related to the particle size. Studies hitherto reported used particles of fraction upto 25 or 50 [mu]m, which generally led to slow kinetics for intraparticle diffusion and consequently long response times.
Another approach of integrating MIPs with transducer component is mixing of graphite or carbon paste, in the MIP matrix (95). In this way, the binding sites and the conducting particles are in close contact. A simple mechanical polishing can renew the sensor surface, hence offering the advantages in the mass production of biomimetic sensors.
MIP-BASED PESTICIDE SENSORS
Pesticides are classified based on their target group as insecticides, fungicides, herbicides and others. Again, based on chemical composition and structure of pesticide, compounds can be categorized into (i) organophosphate, (ii) carbamate, (iii) phenyl urea, (iv) triazine (v) chlorophenoxy acid and (vi) chlorinated hydrocarbon pesticides. Organophosphate Pesticides
Marx et al. (96) developed thin films of molecularly imprinted sol-gel polymer with specific binding sites. The films were cast on glass substrate and on glassy carbon electrodes and were used to detect parathion in aqueous solutions by GC-FPD and cyclic voltammetry. Gas-phase binding measurements were performed on quartz crystal microbalance resonators. The binding was shown to be very sensitive to the type of functional monomer used for imprinting. The imprinted films showed high selectivity towards parathion in comparison to similar organophosphates. Furthermore, the authors discuss difference between molecular recognition in gas- and liquid- phase imprinted polymers. Li et al. (97) fabricated a novel sensor by sol-gel method using p-tert-butyl calix-1,4-crown-4 as functional monomer. A fast response of parathion can be obtained in the range 5 x 10^sup -9^ to 1 x 10^sup -4^ M with a detection limit of 1 x 10^sup -9^ M after incubation in 0.1 M phosphonate buffer solution for 20 minutes. The extremely low detection limit allows the reliable monitoring of parathion in natural waters. The results of the analysis of real samples, such as rice, using the developed sensor compare well with HPLC.
Flow through optosensors developed for carbaryl and warfarin make use of beta-cyclodextrin bound to synthetic polymer (98). The detection limits were reported to be 6.3 x 10^sup -8^ M for warfarin and 6.5 x 10^sup -8^ (aqueous) and 2.5 x 10^sup -8^ M (organic) for carbaryl, respectively. The R. S. Ds are 0.58 (at 1 x 10^sup -6^ M level) and 5% (at 9.45 x 10^sup -7^ M level) for warfarin and carbaryl, respectively. The low detection limits offered by optosensors allow a rapid reliable and precise determination of warfarin and carbaryl in natural waters.
Triazine Herbicides. Electrochemical and optical transducer based biomimetic sensors developed for triazine herbicides (especially atrazine) are summarized in Table 3 (90, 99-109). As seen from Table 3, TSM accoustic (104) and ISFET-QCM-based (105) sensors offer detection limits of 4 ppm (2000 nM) for atrazine which is much higher than maximum permissible limit in drinking water i.e., 3 ppb. On same vein, cyclic voltammetric (106) and Potentiometrie (108) based sensors offer detection limits of 10 ppb for atrazine are lower than above sensors but still higher than maximum permissible limits. Hence, all the above mentioned sensors are useful for monitoring contaminated natural waters. Of these, the potentiometric- based sensor (108) is ideal for field studies. On the other hand, conductometric transducer based atrazine sensor (90, 102-103) allows the monitoring of atrazine both in contaminated and uncontaminated natural waters as the detection limit is 1 ppb. The only draw back is that it required laboratory based instrumentation and is not suitable for field studies. The simplification in instrumentation while designing conductometric sensors will go a long way to solve this problem.
Chlorophenoxy Acid Herbicides. MIP-based recognition materials synthesized by non-covalent imprinting and then coupling with various signal transduction strategies for the detection of 2,4-D are summarized in Table 4 (83, 110-114). Of the few sensors designed for 2,4-D, it is seen from Table 4 that fluorescence (83) and bulk acoustic wave-based (113) sensors alone offer detection limits of 20 ppb (100 nM), which are lower than maximum permissible limit in drinking water, viz. 70 ppb. Hence, these two sensors should find wide application in monitoring contaminated and uncontaminated natural waters. On the other hand, on-line FTIR (112) and electrochemical (111) transducer-based sensors can only be useful in monitoring contaminated natural waters.
MIP-BASED IONOMER SENSORS
Until recently, most of the published accounts for "sensors" have described the phenomena that may lead to a sensing device, not actual devices. Unlike gas sensors, ionic sensors must be used in solution. Mass-sensitive devices such as quartz crystal microbalance or surface wave acoustic sensors cannot usually be employed. The two major methods used for signal transduction in ionic sensors or selectrodes are based on electrochemical and spectroscopic properties (115). The synthesis of polymers exhibiting selective binding of a specific cation involves the formation of cavities equipped with complexing groups or "ligands" so arranged as to match the charge, coordination number, coordination geometry and size of the target cation. The combination of molecular imprinting and transduction selectivities can result in sensors that exclusively recognize target analytes and not interfering species. The selectrodes so far designed for toxic inorganic ions are of two types: (1) Potentioselectrodes (potentiometry transducer based and (2) Optrodes (optical transducer based).
The first imprinted polymer potentioselectrode was described for calcium and magnesium ions by Mosbach's group (116). The monomer used in the fabrication of electrode was a neutral ionophore N,N'- dimethyl-N,N'-bis(4-vinylphenyl)-3-oxapentadiamide. The imprinting process enhanced the selectivity for calcium by factors of 6.0 and 1.7 on calcium binding using Ca^sup 2+^- and Mg^sup 2+^-imprinted polymers respectively, over an unimprinted blank, as measured by back extraction. Murray's group (117) has prepared lead(II) potentioselectrode by employing lead (vinyl benzoateh)^sub 2^ complex for preparing imprinted polymer material. This selectrode results in Nernstian response from 10^sup -6^-10^sup -2^ M of lead(II). In view of this, the developed lead(II) potentioselectrode is not useful for the monitoring of lead(II) in uncontaminated natural water samples as the maximum permissible limit in drinking water is 30 ppb or 1.5 x 10^sup -7^M. The same group (118) has subsequently developed uranyl ion potentioselectrode by employing uranyl-vinyl benzoate/vinyl salicylaldoxime complexes for the preparation of imprinted polymer particles. Our group was successful in fabrication of uranyl (119) and dysprosium ion (49) sensing potentioselectrodes by a single pot synthesis of imprinted polymer particles (sensing materials) with a mixed ligand complex- UO^sup 2+^^sub 2^ /Dy^sup 3+^- 5,7-dichloroquinoline-8-ol-4-vinyl pyridine. In the above-mentioned devices, the IIP particles after leaching imprint ion were dispersed homogenously in a Polyvinylchloride matrix via sonication. The dysprosium ion potentioselectrode senses dysprosium(III) ion in the concentration ranges 8 x 10^sup -6^- 10^sup -1^ M (Nernstian response) with a detection limit of 2 x 10^sup -6^ M while the blank membrane electrode does not respond below 10^sup -4^ M. The selectivity coefficients for dysprosium(III) over alkali, alkaline earth and transition metal ions are in the range of ~10^sup -4^. The dysprosium ion potentioselectrode enables the determination of fluoride in mouthwash solution by an indirect Potentiometrie titration with ethylenediaminetetraacetic acid. On the other hand, the uranyl ion potentioselectrode (schematically shown in Fig. 13) senses uranyl ion in the concentration range 2 x 10^sup -8^ to 1 x 10^sup -2^ M with a detection limit of 2 x 10^sup -8^ or 4.8 ppb. Hence, the developed Potentiometric sensor has the capability of monitoring even uncontaminated natural or sea water samples as the maximum permissible limit for uranium in drinking water is 30 ppb. In addition, the sensor showed a good selectivity for uranyl ion over alkali, alkaline earth, transition and heavy metal ions. The analysis results of sea water samples by uranyl ion sensor is comparable with neutron activation analysis values.
Murray's group (118) has described a fluoro-optrode for the first time by employing lead(II)-methyl-3,5-divinylbenzoate (DVMB) complex during IIP preparation. This optrode was prepared by binding 3% lead(II)-DVMB complex (2% divinylbenzene) by in situ copolymerization on a vinylated 400 [mu]m optical fibre surface. The lead(II) imprint ion was removed from the polymer by first swelling in a mixture of methanol and water and then soaking in stirred solution of EDTA (~1 hour each). The calibration from 70-7 x 10^sup 5^ ppb showed a detection limit of 50 ppb. Unlike the potentioselectrode developed by the same group, the lead(II) optrode can be used for monitoring lead in uncontaminated natural waters as the detection limit is in the same range as that of maximum permissible limit in drinking water, i.e., 30 ppb.
Al-Kindy et al. (120) prepared aluminium sensing materials via non-covalent imprinting technique using the aluminium(III)-morin complex. Based on the fluorescent properties of the chelate, a selective optical flow-through sensor was developed for aluminium. The affinity of the polymer binding sites was higher for aluminium than for other di- and trivalent ions (e.g., Be(II), Ca(II), Mg(II), Eu(III), Zn(II), Fe(III)) suggesting that the nature of metal ion, its ionic radius and the metal-morin stoichiometry play important roles in the ionic recognition.
CONCLUSIONS AND OUTLOOK
We have outlined various synthetic strategies to prepare molecularly imprinted polymer recognition elements and their characterization and transducers employed for converting binding event into a detectable signal. However, one of the fundamental difficulties in the design and development of biomimetic sensors is coupling of chemical recognition element with an appropriate transducer. In spite of this, both electrochemical and opto- electronic transducer-based MIP sensors have been developed for toxic pesticides and inorganics by various researchers. A brief outline of such biomimetic sensors is given.
As mentioned earlier, the low-key attitude in developing electrochemical biomimetic sensors lies in integrating artificial recognition elements with electrochemical transducers. With the developments in MIP technology viz. formation of thin films, composite materials conducting polymers, catalytic polymers etc it is very likely that a new generation of MIP based electrochemical sensors will be established in the next decade. To circumvent the limitations of macroporous cross-linked methacrylate, acrylamide and styrene polymers as materials, other materials and morphologies based on self-assembled monolayers, sol-gels, surface and hierarchial imprinting and several other approaches will be investigated in future. A development worth mentioning for future work is the expanding research on electronic noses and tongues. The development of optical MIP-based sensors essentially rely on chromogenic (either inherent or labeled) or nonchromogenic analytes and majority of them rely upon fluorescence measurements to achieve optimal sensitivity. Thus, it seems that the fluorimetric technique will continue to receive increasing attention. Direct measurements using a variety of sensing devices such as flow analytical devices, wave guide devices, sensing plate devices and fibre optic devices should prove extremely useful.
Historically, regarding the discipline of MIPs and MIP sensor areas as well, most researchers are skilled in polymer chemistry and are interested in polymers rather than sensing. Recently, analytical chemists have realized the potential of MIPs as analytical tool, be it separation or detection and few groups have initiated programmes in this direction. With this changed scenario, one can envisage the fabrication of biomimetic sensors which enable validation and analysis of various environmental, biological, geological and metallurgical samples.
The corresponding author is thankful to Kerala State Committee on Science, Technology and Environment Department (STED), Govt, of Kerala, India for sponsoring a project on "MIPbased sensors for pesticides."
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T. Prasada Rao, K. Prasad, R. Kala, and J. Mary Gladis
Regional Research Laboratory (CSIR), Trivandrum, India
Address correspondence to T. Prasada Rao, Regional Research Laboratory (CSIR), Trivandrum, India. E-mail: tprasadarao(R)rediffmail.com
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