Molecularly Imprinted Polymer Sensor Research Articles

Recognition and Electrochemical Sensing of 8-Hydroxydeoxyguanosine with Molecularly Imprinted Poly (ethylene-<i>co</i>-vinyl alcohol) Thin Films

Biosensors using the mechanisms of electrochemical, optical, mass sensitive thermometric and magnetometric have been intensively investigated [1], and molecularly imprinted polymers (MIPs) has been used as recognition elements in sensors reviewed in numerous articles [1-3]. A severe challenge for MIP sensors is detection in chemically diverse environments, such as biological fluids [4-7]. There are many biomarkers discovered in biological fluid, like cerebrospinal fluid (CSF), saliva, serum and urine. Important biomarkers such as creatinine [4], urea, and albumin [8], urine contains non-protein nitrogen metabolites, carbohydrates [9], proteins and amino acids [10]; detection of analytes must be made amid this complex chemical background.

Electrochemical sensors based on molecularly imprinted polymers grafted onto gold electrodes using click chemistry

We have developed a three-step method to graft molecularly imprinted polymer (MIP) thin films onto Au electrodes. In the first step, propargyl acrylate is clicked onto an azidoundecanethiol (N 3(CH 2) 11SH)/decanethiol mixed self-assembled monolayer (SAM). Then, by applying UV light (365 nm) in the presence of N, N′-methylenebis(acrylamide) (MAAM) and azobisisobutyronitrile (AIBN) as the radical initiator, polymerization was carried out directly on the electrode surface in the presence of an electroactive template molecule, hydroquinone (HQ). Detection of HQ using the clicked-on MIP sensor was studied using chronoamperometry and its behavior was compared to that of a sensor prepared by drop-coating MIPs onto Au. The detection limit of the clicked-on MIP sensor for HQ was found to be 1.21 ± 0.56 μM, about four times lower than what was observed using the coated-on MIP sensor. In addition, the sensitivity of the clicked-on MIP sensor was found to be approximately three times greater than the coated-on MIP sensor. Apparent diffusion coefficients determined using chronoamperometry suggest that the improved performance is likely due to the favorable mass transfer characteristics of the clicked-on MIP sensing membrane.

MIP sensors – the electrochemical approach

This review highlights the importance of coupling molecular imprinting technology with methodology based on electrochemical techniques for the development of advanced sensing devices. In recent years, growing interest in molecularly imprinted polymers (MIPs) in the preparation of recognition elements has led researchers to design novel formats for improvement of MIP sensors. Among possible approaches proposed in the literature on this topic, we will focus on the electrosynthesis of MIPs and on less common hybrid technology (e.g. based on electrochemistry and classical MIPs, or nanotechnology). Starting from the early work reported in this field, an overview of the most innovative and successful examples will be reviewed.

Electrochemical sensor for bisphenol A detection based on molecularly imprinted polymers and gold nanoparticles

A novel bisphenol A (BPA) sensor based on amperometric detection has been developed by using molecularly imprinted polymers (MIPs) and gold nanoparticles. The sensitive layer was prepared by electropolymerization of 2-aminothiophenol on a gold nanoparticles-modified glassy carbon electrode in the presence of BPA as a template. Cyclic voltammetry was used to monitor the process of electropolymerization. The properties of the layer were studied in the presence of Fe(CN)6 3−/Fe(CN)6 4− redox couples. The template and the non-binding molecules were removed by washing with H2SO4 (0.65 mol L−1) solution. The linear response range of the sensor was between 8.0 × 10−6–6.0 × 10−2 mol L−1, with a detection limit of 1.38 × 10−7 mol L−1 (S/N = 3). The proposed MIPs sensor exhibited good selectivity for BPA. The stability and repeatability of the MIPs senor were found to be satisfactory. The results from real sample analysis confirmed the applicability of the MIPs sensor to quantitative analysis.

A strategy for constructing sensitive and renewable molecularly imprinted electrochemical sensors for melamine detection

A novel strategy for preparing highly sensitive and easily renewable molecularly imprinted polymer (MIP) sensors was proposed. Using melamine (MA) as the template molecule, MIP particles were synthesized and embedded in a solid paraffin carbon paste to prepare the MIP sensor. MA was indirectly determined from the competition between the reactions of MA and horseradish peroxidase-labeled MA (MA-HRP) with the vacant cavities. The detection signals were amplified because of enzymatic reaction to the H 2O 2 catalytic oxidation. Sensitivity was markedly improved. Sensor renewal was achieved by a simple mechanical polishing of the sensitive film. The linear range for MA detection was 0.005–1 μmol L −1 and the detection limit was 0.7 nmol L −1. The molecularly imprinted solid paraffin carbon paste sensor was used for MA detection in milk samples.

Molecularly imprinted polymers as optical sensing receptors: Correlation between analytical signals and binding isotherms

Despite the increasing number of usage of molecularly imprinted polymers (MIPs) in optical sensor application, the correlation between the analytical signals and the binding isotherms has yet to be fully understood. This work investigates the relationship between the signals generated from MIPs sensors to its respective binding affinity variables generated using binding isotherm models. Two different systems based on the imprinting of metal ion and organic compound have been selected for the study, which employed reflectance and fluorescence sensing schemes, respectively. Batch binding analysis using the standard binding isotherm models was employed to evaluate the affinity of the binding sites. Evaluation using the discrete bi-Langmuir isotherm model found both the MIPs studied have generally two classes of binding sites that was of low and high affinities, while the continuous Freundlich isotherm model has successfully generated a distribution of affinities within the investigated analytical window. When the MIPs were incorporated as sensing receptors, the changes in the analytical signal due to different analyte concentrations were found to have direct correlation with the binding isotherm variables. Further data analyses based on this observation have generated robust models representing the analytical performance of the optical sensors. The best constructed model describing the sensing trend for each of the sensor has been tested and demonstrated to give accurate prediction of concentration for a series of spiked analytes.

Electrochemical sensor based on a poly( para-aminobenzoic acid) film modified glassy carbon electrode for the determination of melamine in milk

A novel and simple sensor is developed in this paper for melamine detection, which is based on an electropolymerized molecularly imprinted polymer (MIP) of para-aminobenzoic acid ( pABA). The poly( para-aminobenzoic acid) (P- pABA) film was deposited in a pABA solution by potentiodynamic cycling of potential with and without the template (melamine) on a glassy carbon electrode. The surface feature of the modified electrode was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The molecular imprinted sensor was tested by differential pulse voltammetry (DPV) to verify the changes in redox peak currents of hexacyanoferrate. Several important parameters controlling the performance of the P- pABA were investigated and optimized. In the optimal conditions, the relative redox peak currents of hexacyanoferrate were linear. The concentration of melamine ranged from 4.0 μM to 0.45 mM, with a linear correlation coefficient of 0.9992. The detection limit was 0.36 μM (S/N = 3). The MIP sensor was successfully applied to the determination of melamine in milk products and showed high selectivity, sensitivity, and reproducibility. The results of this research demonstrate that it is feasible to use the molecular imprinting methodology when preparing sensing devices for analytes that are electrochemically inactive.

Fabrication of an oxytetracycline molecular-imprinted sensor based on the competition reaction via a GOD-enzymatic amplifier

A highly sensitive molecular-imprinted polymer sensor (MIP sensor) for ultratrace oxytetracycline (OTC) determination was prepared based on the competition reaction between template molecule OTC and glucose oxidase (GOD)-labeled OTC (GOD-OTC). Sensitivity improved dramatically due to the detection of a huge amount of enzyme catalytic production, which was inversely proportional to template molecule concentration. The MIP sensor was characterized by alternating current impedance spectroscopy and cyclic voltammetry, and its voltammetric behavior was also verified. Experimental conditions including isolation, incubation, and competition were optimized. OTC can be determined at concentrations between 0 and 4.0 × 10 −7 mol/L with a detection limit of 3.30 × 10 −10 mol/L by the differential pulse voltammetry technique. The MIP sensor showed high sensitivity, selectivity, reproducibility, and good recovery in sample determination.

Molecularly imprinted polymer sensor arrays

The sensor array format has proved an effective method of transforming sensors of modest selectivity into highly selective and discriminating sensors. The primary challenge in developing new sensor arrays is collecting together a sufficient number of recognition elements that possess different binding affinities for the analytes of interest. In this regard, the use of molecularly imprinted polymers (MIPs) as the recognition elements in sensor arrays has a number of unique advantages. MIPs can be rapidly and inexpensively prepared with different selectivities and tuned with different selectivity patterns via the choice of templates in the imprinting process. The array format also helps compensate for the low selectivities and high cross-reactivities of MIP sensors. These attractive qualities of MIP sensor arrays have been demonstrated in recent examples, which have established the viability and generality of the approach. In particular, the versatility of the imprinting process enables MIP sensor arrays to be tailored to specific analytes. MIP sensor arrays have also shown surprisingly broad utility, as even analytes that were not used as templates in the imprinting process can be effectively discriminated.

Molecularly Imprinted Electrochemical Sensors

AbstractIn this review, the applications of molecularly imprinted polymer (MIP) materials in the area of electrochemical sensors have been explored. The designs of the MIPs containing different polymers, their preparation and their immobilization on the transducer surface have been discussed. Further, the employment of various transducers containing the MIPs based on different electrochemical techniques for determining analytes has been assessed. In addition, the general protocols for getting the electrochemical signal based on the binding ability of analyte with the MIPs have been given. The review ends with describing scope and limitations of the above electrochemical based MIP sensors.

Layer-by-layer assembly sensitive electrochemical sensor for selectively probing l-histidine based on molecular imprinting sol–gel at functionalized indium tin oxide electrode

A novel sensitive and selective imprinted electrochemical sensor was successfully constructed for the direct detection of l -histidine by combination of a molecular imprinting film and multi-walled carbon nanotubes (MWNTs). The sensor was fabricated onto an indium tin oxide (ITO) electrode via stepwise modification of MWNTs and a thin film of molecularly imprinted polymers (MIPs) via sol–gel technology. The introduced MWNTs exhibited noticeable enhancement on the sensitivity of the MIPs sensor. Meanwhile, the molecularly imprinted film displayed high sensitivity and excellent selectivity for the target molecule l -histidine. The proposed imprinted sensor was characterized by using scanning electron microscope (SEM) and electrochemical methods involving cyclic voltammetry (CV), differential pulse voltammetry (DPV) and amperometric i–t curve. A linear ranging from 2.0 μmol L −1 to 1.0 mmol L −1 for the detection of l -histidine was observed with the detection limit of 5.8 × 10 −9 mol L −1 for S/N = 3. This imprinted electrochemical sensor was successfully employed to detect l -histidine in human blood serum.

Reading microdots of a molecularly imprinted polymer by surface-enhanced Raman spectroscopy

Writing a molecularly imprinted polymer (MIP) by nano-fountain pen on surface-enhanced Raman scattering (SERS)-active surfaces resulted in site-controlled arrays of microdots of approximately 6–12 μm in diameter. The monitoring of SERS spectra with a micro-Raman system enabled examining the uptake and release of the S-propranolol imprinting template and allowed imaging individual dots as well as multiple dots in an array, revealing the distribution of the imprinted polymer. This distribution was confirmed by atomic force microscopy, showing that even in dots of <300 nm thickness, corresponding to MIP volumes of 0.5 fl, significantly less than previously reported, the target analyte could be detected and identified. This study shows that nanolithography techniques combined with SERS might open the possibility of miniaturized arrayed MIP sensors with label-free, specific and quantitative detection.

Electrochemical sensor for parabens based on molecular imprinting polymers with dual-templates

A selective, sensitive, rapid and reliable method based on molecularly imprinted polymers (MIPs) with dual templates to determine total content of parabens in cosmetics was developed. With methylparaben (MP) and propylparaben (PP) as dual-templates, methacrylic acid (MAA) as a functional monomer and tripropylene glycol diacrylate (TPGDA) as a cross-linker, MIPs film on a glassy carbon electrode was constructed as paraben sensor. At oxidation potential of 0.94 V ( vs. SCE), the peak currents on the MIPs sensor were proportional to the concentration of parabens with square wave voltammetry. As the ratio of MP to PP in the MIPs was 1:1.25, the regression equations for four parabens were almost the same. The linear range was 20–100 μM for MP and EP, 5–100 μM for PP, and 5–80 μM for BP, with detection limit of 0.4 μM for MP and EP, 0.2 μM for the others. The total content of parabens could be calculated according to the average of these four regress equations. At least 10 times of structural analogs, such as p-hydroxybenzoic acid, p-aminobenzoic acid and phenol would not interfere with the determination of parabens. Nonanalogous coexistences such as vitamin C had no response on the sensor at all. Rapid response of the MIPs sensor was obtained within 1 min. MIPs sensor had been used to determine total content of parabens in cosmetic samples with recoveries between 98.7% and 101.8%. It reveals that the MIPs sensor with multi-templates has a potential to determine the total content of a group of homologous compounds.

Electrochemical sensor based on molecular imprinting by photo-sensitive polymers

A novel voltammetric sensor based on molecularly imprinted polymers (MIPs) by a kind of photo-sensitive functional polymer was developed for determination of glucose in this work. Without the cross-linker and the initiator, a MIPs film on the surface of a gold electrode was easily formed by in-situ cross-link within 10 min under UV light irradiation. In alkaline medium, electrochemical oxidation behaviors of glucose on the MIPs sensor, as well as on a bare gold electrode have been investigated with square wave voltammetry. At oxidation potential of −0.50 V ( vs. SCE), the peak currents on the MIPs sensor were proportional to the concentration of glucose in the range of 5.0–120 μM with the detection limit of 0.2 μg ml −1 (S/N = 3), whereas the extremely small responses of the control electrode were observed and independent of the analyte concentration. MIPs sensor displayed specific selectivity toward glucose in comparison to structurally similar analogues. The selective coefficient of glucose MIPs sensor with respect to maltose, arabinose and mannose was 9.17, 1.51 and 1.25, respectively. Fructose and inositol would not interfere with the determination of glucose because they could not be electrochemically oxidized at the potential of −0.50 V. Relative rapid response of the MIPs sensor was obtained within 7 min, and the RSD of peak currents was 5.0% ( n = 5). MIPs sensor was applied to determine glucose in the simulative blood serum samples, the average recoveries was 92.6%. The experimental results showed that the sensor for glucose, based on MIPs by photo-sensitive polymers, was simpler to construct and operate, and provided an adequate sensitivity, good repeatability and accuracy and acceptable selectivity.

Astrobiological molecularly imprinted polymer sensors

The purpose of the Astrobiological MIP Sensor (AMS) Project is to develop reliable, low-cost, low-mass, low-power consumption detection technologies for in situ analysis of biochemical markers, and other indicators of astrobiological importance. To this end, we are investigating the potential role that molecularly imprinted polymers (MIP) could serve in the recognition of pre-biotic and biotic compounds in planetary, astrobiological and geochemical mission profiles. While MIPs are effective molecular recognition tools, a signal transduction method must be developed so that the recognition of analytes can be realized. In the course of this study, surface plasmon resonance (SPR) will be the detection method of the MIP recognition event. In addition, MIP-coated SPR substrates were subjected to vibration, temperature and radiation testing to demonstrate that they could withstand the rigors of space travel. The methods developed in this study require capture of the biomarkers onto the SPR sensor chip, followed by addition of a MIP. It is the binding of the MIP to the SPR bound analyte that amplifies the SPR signal associated with binding of the low molecular weight analyte. The MIPs, developed in this study are water-soluble processable star polymers while the SPR device used was SensíQ™ by Nomatics. Proof-of-principal experiments were first demonstrated using amino biotin.

Development of a piezoelectric sensor for the detection of methamphetamine

A computationally designed molecularly imprinted polymer (MIP) specific for methamphetamine was used as a synthetic receptor for the development of a piezoelectric sensor. Several different protocols were tested for the immobilisation of the MIP onto the gold sensor surface. The developed MIP sensor had a detection limit for methamphetamine as low as 1 microg mL(-1). The effect of the addition of poly(vinyl acetate) (PVA) on the pre-polymerisation mixtures, which increases the porosity of the polymer layer, was also studied using an Atomic Force Microscope (AFM). PVA seemed to affect both the porosity and the binding kinetics of the polymers prepared in dimethylformamide (DMF). However, no clear effect on porosity and binding kinetics was observed when polymers were prepared in diglyme. Moreover, PVA did not appear to improve the amplitude of the sensor response. In conclusion, because of its excellent recognition ability in aqueous solutions, the sensor described in this work could be an ideal starting point for the development of a commercial device for fast, on-site or road-side testing of drugs of abuse in body fluids such as saliva.

Ascorbic acid sensor based on molecularly imprinted polymer-modified hanging mercury drop electrode

Ascorbic acid sensor based on molecularly imprinted polymer (MIP) is reported for sensitive and selective analysis, without any cross-reactivity or matrix effect, in aqueous, blood serum and pharmaceutical samples. The sensor was developed by the direct coating of ascorbic acid-imprinted polymer, prepared from melamine and chloranil, on the surface of a hanging mercury drop electrode (HMDE) at + 0.4 V (vs. Ag/AgCl). The molecular recognition of ascorbic acid was highly specific using non-covalent (hydrophobically driven hydrogen-bonding and electrostatic) interactions. The analyte was preconcentrated and oxidised instantaneously in the imprinted polymer layer giving voltammetric signal on cathodic stripping at optimised operational conditions: accumulation potential + 0.4 V (vs. Ag/AgCl), polymer deposition time 120 s, template accumulation time 120 s, pH 7.0, scan rate 10 mV s − 1 , pulse amplitude 25 mV. The proposed MIP sensor is able to enhance sensitivity substantially so as to detect serum ascorbic acid level as low as 0.26 ng mL − 1 (R.S.D. 0.5%, S/N 3) for the diagnosis of hypovitaminosis C (Vitamin C deficiency).

From biosensor to biochip

Sense organs have developed during evolution as the organism has adapted to its environment. They recognize chemical signals by binding to structurally complementary receptor areas, which is followed by the transduction of this event into electrical nerve impulses. Biosensors represent the technological counterpart of our sense organs, coupling the recognition by a biological recognition element with a chemical or physical transducer (Table 1), transferring the signal to the electrical domain. The characteristic feature of the biosensor is, according to the definition of IUPAC, the direct (spatial) contact of the recognition element and the transducer. This integration leads to a compact functional unit which allows re-usage of the biological component and miniaturization of the sensor body. These properties allow for online measurement and are the basis of the combination of different recognition elements on one transducer array in the biochip. Integration of the biochemical and electronic signal processing has been realized in ‘intelligent biosensors’ and BioFETs, respectively. The combination of the biosensor with microfludics and actuators on a chip has led to total microanalysis systems (μTAS). The biosensor definition may also be extended in respect to biomimetic recognition elements, e.g. aptamers and molecularly imprinted polymers, which are derived from biology (Table 1). In this series the most challenging developments -, i.e. in vivo sensing, biomimetic recognition and optical array technology – are reviewed by internationally recognized experts. As early as 1962, L. Clark claimed in his enzyme electrode patent the potential application for online blood glucose monitoring. In spite of several breakthroughs, long-term blood glucose monitoring is still not a reality. Molecularly imprinted polymers (MIPs) contain tailor-made binding sites for a given target molecule mimicking biological receptors and enzymes. MIP sensors include not only low molecular substances but also proteins, nucleic acids and even viruses and microorganisms. Highly parallel measurements are well established in DNA chip technology. However, this concept relies on sequential signal evaluation. Recent concepts of both DNA and protein arrays use individually addressable microelectrodes or optical fibre bundles. We hope that the three articles of this minreview series on biosensors will stimulate new interdisciplinary discussions and collaborations.

Development of a Molecularly Imprinted Biomimetic Electrode

The technique of molecular imprinting produces artificial receptor sites in apolymer that can be used in a biomimetic sensor. This research extends previous studies ofa molecularly imprinted polymer (MIP) biomimetic sensor for the small drug theophylline.The presence of theophylline in the biomimetic sensor was monitored by analyzing thepeak currents from cyclic voltammetry experiments. The functional working range of theMIP modified electrode was 2 - 4 mM theophylline. The concentration of theophyllinethat resulted in the best signal was 3 mM. The MIP sensor showed no response to thestructurally related molecule caffeine, and therefore was selective to the target analytetheophylline. This research will provide the foundation for future studies that will result indurable biomimetic sensors that can offer a viable alternative to current sensors.

Molecularly imprinted solid‐phase extraction combined with molecularly imprinted polymer‐sensor: a diagnostic tool applicable to creatine deficiency syndrome

Primary creatine deficiency syndromes (CDS) are a new group of disorders caused by guanidinoacetate methyltransferase (GAMT) deficiency, which affects endogenous creatine biosynthesis with depletion of body creatine. A deficiency in creatine can be corrected by treatment with oral creatine supplementation and this necessitates a simple and sensitive screening method for early detection of creatine in dilute physiologic fluids. In this work an artificial receptor, molecularly imprinted polymer (MIP), for creatine was used both as a material for solid-phase extraction (SPE) and as a sensing element in a voltammetric sensor. Using the combination of molecularly imprinted solid-phase extraction (MISPE) with a complementary MIP sensor, the minimum detectable amount was found to be 0.0015 ng mL(-1) (RSD = 1.3%, S/N = 3). The MISPE-MIP sensor combination provided up to 60-fold preconcentration, which was more than sufficient for achieving the required quantification limit 50 ng mL(-1) (or 0.0025 ng mL(-1) after 2 x 10(4)-fold dilution) for creatine in human blood serum.